Background O
Chemotherapy O
- O
induced O
cardiomyopathy O
( O
CICM O
) O
and O
heart O
failure O
are O
major O
complications O
of O
cancer O
therapeutics O
and O
can O
result O
in O
significant O
morbidity O
and O
mortality O
. O
There O
is O
limited O
data O
on O
the O
incidence B-EPI
and O
risk O
factors O
of O
CICM O
in O
African O
American O
and O
Afro O
- O
Caribbean O
patients O
. O
Methods O
We O
performed O
a O
retrospective O
chart O
review O
to O
evaluate O
the O
baseline O
characteristics O
that O
may O
predispose O
to O
CICM O
. O
Patients O
were O
African O
American O
and O
Afro O
- O
Caribbean O
ethnicity O
. O
Data O
was O
collected O
between O
2014 O
to O
2018 O
. O
Patients O
had O
transthoracic O
echocardiogram O
( O
TTE O
) O
or O
multigated O
acquisition O
scan O
( O
MUGA O
) O
prior O
to O
cancer O
therapy O
and O
every O
3 O
months O
thereafter O
, O
until O
the O
end O
of O
the O
regimen O
. O
CICM O
was O
defined O
as O
a O
≥16 O
% O
reduction O
in O
LVEF B-LOC
or O
≥10 O
% O
reduction O
in O
LVEF B-LOC
to O
a O
value O
< B-STAT
50 I-STAT
% I-STAT
. O
Results O
A O
total O
of O
230 O
patients O
were O
studied O
, O
with O
a O
mean O
age O
of O
54±12 O
years O
with O
91 O
% O
were O
females O
, O
BMI O
30±4 O
, O
81 O
% O
were O
taking O
anthracyclines O
, O
87 O
% O
were O
on O
Trastuzumab B-LOC
while O
5 O
% O
were O
receiving O
both O
medications O
. O
The O
prevalence B-EPI
of O
comorbidities O
was O
as O
follows O
: O
hypertension O
8 O
% O
, O
diabetes O
mellitus O
8 O
% O
, O
ESRD O
8 O
% O
, O
dyslipidemia O
8 O
% O
, O
CAD O
7 B-STAT
% I-STAT
. O
The O
incidence B-EPI
of O
CICM O
was O
7 O
% O
overall O
, O
while O
it O
was O
6 O
% O
and O
8 O
% O
for O
patients O
taking O
Anthracyclines O
and O
Trastuzumab B-LOC
, O
respectively O
. O
CICM O
was O
associated O
with O
dyslipidemia O
( O
r= O
.22 O
, O
p= O
.001 O
) O
, O
hypertension O
( O
r= O
.12 O
, O
p= O
.05 O
) O
, O
baseline O
ejection O
fraction O
( O
r= O
-.21 O
, O
p= O
.001 O
) O
and O
concomitant O
use O
of O
radiation O
therapy O
( O
r= O
.147 O
, O
p= O
.02 O
) O
, O
but O
not O
with O
age O
, O
gender O
, O
beta O
blocker O
use O
, O
angiotensin O
converting O
enzyme O
inhibitor O
use O
, O
number O
of O
chemotherapy O
cycles O
or O
stage O
of O
the O
malignancy O
. O
On O
multivariate O
analysis O
CICM O
was O
independently O
associated O
with O
baseline O
ejection O
fraction O
( O
β= O
-.193 O
, O
P= O
.003 O
) O
and O
dyslipidemia O
( O
β= O
-.20 O
, O
P= O
.003 O
) O
. O
Conclusion O
The O
incidence B-EPI
of O
CICM O
in O
African O
Americans O
and O
Afro O
- O
Caribbean O
is O
higher O
than O
reported O
in O
the O
general O
population O
. O
Dyslipidemia O
and O
baseline O
ejection O
fraction O
were O
seen O
as O
the O
major O
risk O
factors O
associated O
with O
the O
higher O
incidence B-EPI
of O
CICM O
. O
Background O
Cardiac O
rupture O
is O
a O
disastrous O
but O
uncommon O
complication O
of O
acute O
ST B-LOC
- O
elevation O
myocardial O
infarction O
( O
STEMI O
) O
. O
The O
incidence B-EPI
, O
risk O
factors O
and O
in O
- O
hospital O
outcomes O
related O
to O
cardiac O
rupture O
in O
the O
current O
era O
are O
unknown O
. O
Methods O
This O
study O
consecutively O
collected O
all O
acute O
STEMI O
patients O
admitted O
to O
a O
single O
tertiary O
center O
in O
China B-LOC
from O
January O
2004 O
to O
December O
2015 O
. O
Characteristics O
of O
each O
cardiac O
rupture O
were O
collected O
and O
analyzed O
. O
Results O
Among O
4190 O
patients O
, O
75 B-STAT
( O
1.8 O
% O
) O
patients O
had O
cardiac O
rupture O
, O
including O
33 O
at O
the O
ventricular O
septum O
and O
42 O
at O
the O
left O
ventricle O
free O
wall O
( O
LVFW O
) O
. O
Patients O
with O
cardiac O
rupture O
were O
more O
likely O
to O
be O
female O
, O
with O
more O
advanced O
age O
, O
lower O
rate O
of O
primary O
percutaneous O
coronary O
intervention O
( O
PPCI O
) O
, O
and O
higher O
in O
- O
hospital O
mortality O
. O
Compared O
with O
survivors O
, O
the O
death O
cases O
were O
older O
, O
had O
a O
higher O
white O
blood O
cell O
count O
, O
higher O
rate O
of O
delayed O
admission O
( O
> O
12 O
h O
from O
symptom O
onset O
to O
door O
) O
, O
earlier O
occurrence B-EPI
of O
cardiac O
rupture O
, O
higher O
percentage O
of O
LVFW O
rupture O
and O
lower O
rate O
of O
surgical O
repair O
. O
Logistic O
regression O
analysis O
showed O
that O
surgical O
repair O
served O
as O
the O
most O
valuable O
factor O
affecting O
survival O
. O
Moreover O
, O
elevated O
white O
blood O
cell O
count O
and O
advanced O
age O
might O
be O
related O
to O
an O
increased O
in O
- O
hospital O
death O
due O
to O
cardiac O
rupture O
. O
Conclusions O
In O
this O
contemporary O
cohort O
, O
female O
sex O
, O
advanced O
age O
and O
low O
rate O
of O
PPCI O
post O
- O
STEMI O
are O
associated O
with O
an O
increased O
risk O
of O
cardiac O
rupture O
. O
Advanced O
age O
and O
elevated O
white O
blood O
cell O
count O
might O
be O
related O
to O
an O
increased O
in O
- O
hospital O
mortality O
after O
cardiac O
rupture O
, O
whereas O
surgical O
repair O
served O
as O
the O
most O
valuable O
factor O
affecting O
survival O
. O
Background O
Nonarteritic O
anterior O
ischemic O
optic O
neuropathy O
( O
NAION O
) O
in O
young O
patients O
( O
age O
≤50 O
) O
accounts O
for O
a O
minority O
of O
all O
cases O
of O
NAION O
and O
is O
more O
highly O
associated O
with O
crowding O
of O
the O
optic O
nerves O
and O
bilateral O
involvement O
than O
NAION O
in O
older O
patients O
. O
Optic O
disc O
drusen O
( O
ODD O
) O
are O
likewise O
associated O
with O
crowded O
optic O
nerves O
and O
are O
located O
in O
the O
prelaminar O
optic O
nerve O
head O
where O
they O
could O
contribute O
to O
NAION O
pathogenesis O
. O
The O
purpose O
of O
this O
study O
was O
to O
determine O
the O
prevalence B-EPI
of O
ODD O
in O
the O
eyes O
of O
young O
NAION O
patients O
using O
modern O
imaging O
methods O
and O
to O
compare O
it O
to O
the O
baseline O
1.8%-2.0 B-STAT
% I-STAT
prevalence B-EPI
of O
ODD O
in O
the O
general O
population O
. O
Methods O
In O
this O
retrospective O
study O
, O
all O
young O
NAION O
patients O
( O
ages O
18 O
- O
50 O
years O
, O
inclusive O
) O
seen O
in O
2 O
tertiary O
care O
neuro O
- O
ophthalmology O
clinics O
( O
in O
London B-LOC
, O
Canada B-LOC
and O
Copenhagen B-LOC
, O
Denmark B-LOC
) O
in O
the O
ten O
- O
year O
interval O
between O
April O
1 O
, O
2009 O
, O
and O
March O
31 O
, O
2019 O
, O
were O
identified O
and O
their O
medical O
charts O
reviewed O
. O
Patients O
were O
included O
in O
the O
study O
if O
ODD O
were O
diagnosed O
by O
any O
method O
( O
including O
ophthalmoscopy O
, O
ultrasound O
[ O
US B-LOC
] O
, O
fundus O
autofluorescence O
[ O
FAF O
] O
, O
computed O
tomography O
[ O
CT O
] O
, O
or O
any O
optical O
coherence O
tomography O
[ O
OCT O
] O
method O
) O
, O
or O
if O
ODD O
were O
excluded O
by O
enhanced O
- O
depth O
imaging O
OCT O
( O
EDI O
- O
OCT O
) O
using O
the O
ODD O
Studies O
( O
ODDS O
) O
Consortium O
protocol O
. O
The O
presence O
or O
absence O
of O
ODD O
was O
recorded O
for O
each O
eye O
. O
Results O
There O
were O
37 O
eligible O
patients O
( O
74 O
eyes O
) O
. O
Mean O
age O
of O
NAION O
onset O
was O
38.5 O
± O
10.0 O
years O
, O
and O
23 O
patients O
( O
62 O
% O
) O
were O
men O
. O
Patients O
had O
undergone O
the O
following O
methods O
of O
ODD O
detection O
: O
ophthalmoscopy O
( O
37 O
patients O
) O
, O
EDI O
- O
OCT O
( O
36 O
patients O
) O
, O
FAF O
( O
31 O
patients O
) O
, O
US B-LOC
( O
9 O
patients O
) O
, O
and O
CT O
orbits O
( O
8 O
patients O
) O
. O
We O
found O
a O
prevalence B-EPI
of O
ODD O
of O
56.7 O
% O
in O
NAION O
- O
affected O
patients O
and O
53.3 O
% O
in O
NAION O
- O
affected O
eyes O
. O
Only O
35.9 O
% O
of O
ODD O
were O
visible O
on O
ophthalmoscopy O
. O
Twenty O
of O
21 O
ODD O
patients O
( O
95.2 O
% O
) O
had O
bilateral O
ODD O
. O
Age O
of O
onset O
and O
sex O
did O
not O
differ O
significantly O
between O
the O
ODD O
- O
positive O
group O
and O
the O
ODD O
- O
negative O
group O
. O
EDI O
- O
OCT O
outperformed O
any O
combination O
of O
ophthalmoscopy O
, O
US B-LOC
, O
FAF O
, O
and O
CT O
at O
detecting O
ODD O
. O
Conclusion O
ODD O
were O
found O
with O
much O
higher O
prevalence B-EPI
in O
young O
patients O
with O
NAION O
than O
in O
the O
general O
population O
and O
were O
usually O
bilateral O
and O
buried O
. O
ODD O
may O
contribute O
to O
NAION O
pathogenesis O
by O
exacerbating O
an O
underlying O
compartment O
syndrome O
in O
the O
crowded O
O
disc O
at O
risk O
. O
O
EDI O
- O
OCT O
may O
be O
the O
best O
imaging O
modality O
for O
ODD O
detection O
in O
future O
studies O
. O
Background O
Pseudohypoparathyroidism O
( O
PHP O
, O
OMIM O
# O
103580 O
) O
is O
a O
very O
rare O
disease O
( O
incidence B-EPI
0.3 B-STAT
- I-STAT
1/100,000 I-STAT
) O
. O
Heterozygous O
inactivating O
mutations O
involving O
the O
maternal O
GNAS O
exons O
1 B-STAT
- I-STAT
13 I-STAT
that O
encodes O
the O
alpha O
subunit O
of O
the O
stimulatory O
G O
protein O
( O
Gsα O
) O
cause O
inactivating O
parathyroid O
hormone O
( O
PTH)/PTHrP O
signalling O
disorder O
type O
2 O
( O
iPPSD2 O
or O
PHP O
type O
1A O
) O
, O
which O
is O
characterized O
by O
Albright O
hereditary O
osteodystrophy O
and O
resistance O
to O
multiple O
hormones O
that O
act O
through O
the O
Gsα O
signalling O
pathway O
( O
including O
PTH O
, O
thyroid O
- O
stimulating O
hormone O
, O
and O
α O
- O
melanocyte O
- O
stimulating O
hormone O
) O
. O
To O
date O
, O
little O
information O
is O
available O
on O
craniofacial O
features O
in O
patients O
with O
PHP O
. O
The O
small O
number O
of O
patients O
studied O
in O
previous O
reports O
as O
well O
as O
the O
lack O
of O
molecular O
characterization O
of O
the O
patients O
may O
have O
precluded O
the O
detection O
of O
specific O
orofacial O
manifestations O
in O
the O
different O
PHP O
subtypes O
. O
Materials O
/ O
methods O
We O
conducted O
a O
systematic O
analysis O
of O
dental O
and O
craniofacial O
features O
in O
19 O
patients O
with O
iPPSD2 O
and O
maternal O
GNAS O
inactivating O
mutations O
to O
assess O
the O
frequency O
and O
specificity O
of O
the O
anomalies O
. O
Results O
Facial O
examinations O
showed O
reduced O
vertical O
, O
sagittal O
, O
and O
transverse O
development O
of O
the O
mid O
- O
facial O
structures O
. O
Intraoral O
and O
radiographic O
examinations O
revealed O
that O
89 O
per O
cent O
of O
the O
patients O
had O
at O
least O
one O
dental O
anomaly O
, O
including O
tooth O
submergence O
leading O
to O
severe O
infraocclusion O
in O
83 O
per O
cent O
of O
cases O
. O
Craniofacial O
analysis O
of O
lateral O
cephalometric O
radiographs O
also O
showed O
a O
significant O
alteration O
in O
the O
development O
of O
the O
cranial O
base O
and O
maxillary O
and O
mandibular O
structures O
in O
these O
patients O
. O
Conclusions O
Patients O
with O
iPPSD2 O
and O
maternal O
GNAS O
mutations O
had O
specific O
craniofacial O
alterations O
and O
dental O
abnormalities O
. O
These O
specific O
defects O
should O
be O
assessed O
in O
order O
to O
provide O
appropriate O
dental O
and O
orthodontic O
care O
to O
these O
patients O
. O
( O
clinical O
trial O
registration O
: O
1920371 O
v O
0 O
, O
French O
Nationale O
Data O
Processing O
and O
Liberties O
Commission O
- O
CNIL O
) O
. O
Objective O
The O
aim O
of O
the O
current O
study O
was O
to O
compare O
the O
risk O
and O
also O
the O
types O
of O
ictal O
injuries O
in O
three O
groups O
of O
people O
with O
seizures O
[ O
i.e. O
, O
IGE O
vs. O
TLE O
vs. O
FS O
] O
. O
Methods O
This O
was O
a O
retrospective O
study O
. O
All O
patients O
with O
an O
electro O
- O
clinical O
diagnosis O
of O
IGE O
, O
TLE O
, O
or O
FS O
were O
recruited O
at O
the O
outpatient O
epilepsy O
clinic O
at O
Shiraz O
University O
of O
Medical O
Sciences O
, O
Shiraz B-LOC
, O
Iran B-LOC
, O
from O
2008 O
until O
2020 O
. O
Age O
, O
sex O
, O
age O
at O
seizure O
onset O
, O
seizure O
type(s O
) O
, O
and O
occurrence B-EPI
of O
ictal O
injury O
at O
any O
time O
since O
the O
onset O
of O
the O
seizures O
and O
its O
characteristics O
were O
registered O
routinely O
for O
all O
patients O
at O
the O
time O
of O
the O
first O
visit O
. O
Results O
One O
thousand O
and O
one O
hundred O
seventy O
- O
four O
patients O
were O
studied O
( O
481 O
patients O
with O
IGE O
, O
402 O
people O
with O
TLE O
, O
and O
291 O
persons O
with O
FS O
) O
. O
While O
the O
groups O
differed O
in O
their O
demographic O
and O
clinical O
characteristics O
, O
the O
rates O
of O
ictal O
injury O
did O
not O
differ O
significantly O
between O
the O
groups O
. O
Tongue O
injury O
was O
more O
frequently O
reported O
by O
patients O
with O
TLE O
compared O
with O
that O
by O
people O
with O
IGE O
or O
FS O
. O
Other O
types O
/ O
locations O
of O
ictal O
injury O
were O
more O
or O
less O
reported O
by O
all O
three O
groups O
of O
the O
patients O
. O
Conclusion O
Ictal O
injuries O
may O
happen O
with O
more O
or O
less O
similar O
rates O
among O
people O
with O
epilepsy O
( O
IGE O
and O
TLE O
) O
and O
those O
with O
FS O
. O
Ictal O
injury O
( O
rate O
, O
type O
, O
or O
location O
) O
should O
not O
be O
used O
as O
a O
marker O
for O
any O
specific O
diagnosis O
among O
people O
with O
seizures O
. O
Inherited O
retinal O
diseases O
( O
IRDs O
) O
, O
which O
are O
among O
the O
most O
common O
genetic O
diseases O
in O
humans O
, O
define O
a O
clinically O
and O
genetically O
heterogeneous O
group O
of O
disorders O
. O
Over O
80 O
forms O
of O
syndromic O
IRDs O
have O
been O
described O
. O
Approximately O
200 O
genes O
are O
associated O
with O
these O
syndromes O
. O
The O
majority O
of O
syndromic O
IRDs O
are O
recessively O
inherited O
and O
rare O
. O
Many O
, O
although O
not O
all O
, O
syndromic O
IRDs O
can O
be O
classified O
into O
one O
of O
two O
major O
disease O
groups O
: O
inborn O
errors O
of O
metabolism O
and O
ciliopathies O
. O
Besides O
the O
retina O
, O
the O
systems O
and O
organs O
most O
commonly O
involved O
in O
syndromic O
IRDs O
are O
the O
central O
nervous O
system O
, O
ophthalmic O
extra O
- O
retinal O
tissues O
, O
ear O
, O
skeleton O
, O
kidney O
and O
the O
cardiovascular O
system O
. O
Due O
to O
the O
high O
degree O
of O
phenotypic O
variability O
and O
phenotypic O
overlap O
found O
in O
syndromic O
IRDs O
, O
correct O
diagnosis O
based O
on O
phenotypic O
features O
alone O
may O
be O
challenging O
and O
sometimes O
misleading O
. O
Therefore O
, O
genetic O
testing O
has O
become O
the O
benchmark O
for O
the O
diagnosis O
and O
management O
of O
patients O
with O
these O
conditions O
, O
as O
it O
complements O
the O
clinical O
findings O
and O
facilitates O
an O
accurate O
clinical O
diagnosis O
and O
treatment O
. O
Background O
Metabolic O
syndrome O
( O
MetS O
) O
is O
a O
major O
risk O
factor O
for O
cardiovascular O
diseases O
. O
The O
objective O
of O
the O
study O
was O
to O
evaluate O
the O
updated O
prevalence B-EPI
of O
MetS O
and O
provide O
a O
comprehensive O
illustration O
of O
the O
possible O
temporal O
changes O
in O
MetS O
prevalence B-EPI
in O
China B-LOC
from O
2011 O
to O
2015 O
. O
Methods O
The O
data O
for O
this O
study O
are O
from O
the O
2011 O
and O
2015 O
waves O
of O
the O
China O
Health O
and O
Retirement O
Longitudinal O
Study O
( O
CHARLS O
) O
. O
CHARLS O
is O
a O
nationally O
representative O
survey O
targeting O
populations O
aged O
45 O
and O
above O
from O
28 O
provinces O
in O
mainland O
China B-LOC
. O
A O
total O
of O
11,847 O
and O
13,013 O
participants O
were O
eligible O
for O
data O
analysis O
at O
the O
two O
time O
points O
. O
Results O
The O
estimated B-EPI
prevalence I-EPI
of O
MetS O
in O
2015 O
was O
20.41 O
% O
( O
95 O
% O
CI O
: O
19.02 B-STAT
- O
21.8 O
% O
) O
by O
the O
National O
Cholesterol O
Education O
Program O
( O
NCEP O
) O
Expert O
Panel O
on O
Detection O
, O
Evaluation O
, O
and O
Treatment O
of O
High O
Blood O
Cholesterol O
in O
Adults O
( O
ATP O
III O
) O
criteria O
, O
34.77 O
% O
( O
95 O
% O
CI O
: O
33.12 O
- O
36.42 O
% O
) O
by O
the O
International O
Diabetes O
Federation O
( O
IDF O
) O
criteria O
, O
39.68 O
% O
( O
95 O
% O
CI O
: O
37.88 O
- O
41.47 O
% O
) O
by O
the O
revised O
ATP O
III O
criteria O
, O
and O
25.55 O
% O
( O
95 O
% O
CI O
: O
24.19 O
- O
26.91 O
% O
) O
by O
the O
Chinese O
Diabetes O
Society O
( O
CDS O
) O
criteria O
. O
The O
prevalence B-EPI
was O
higher O
among O
women O
and O
elderly O
adults O
and O
in O
urban O
and O
northern O
populations O
. O
Furthermore O
, O
the O
trends O
in O
the O
prevalence B-EPI
decreased O
significantly O
between O
2011 O
and O
2015 O
by O
the O
ATP O
III O
, O
revised O
ATP O
III O
and O
CDS O
criteria O
. O
However O
, O
trends O
increased O
significantly O
from O
2011 O
to O
2015 O
by O
the O
IDF O
criteria O
. O
Conclusions O
A O
higher O
prevalence B-EPI
of O
MetS O
is O
found O
in O
those O
who O
reported O
being O
middle O
aged O
and O
elderly O
, O
women O
, O
residing O
in O
northern O
China B-LOC
or O
living O
in O
urban O
areas O
. O
Additionally O
, O
temporal O
changes O
in O
the O
prevalence B-EPI
of O
MetS O
varied O
according O
to O
different O
criteria O
. O
Increased O
attention O
to O
the O
causes O
associated O
with O
populations O
who O
have O
higher O
levels O
of O
MetS O
is O
warranted O
. O
Background O
Hypertension O
is O
prevalent B-EPI
in O
35%-46 O
% O
of O
the O
general O
population O
; O
1 O
% O
of O
them O
experience O
accelerated O
hypertension O
. O
Among O
patients O
with O
accelerated O
hypertension O
, O
acute O
worsening O
of O
renal O
functions O
occur O
in O
22%-55 O
% O
. O
Morbidity O
and O
mortality O
rates O
are O
high O
. O
Partial O
renal O
recovery O
is O
seen O
in O
some O
, O
while O
others O
rapidly O
progress O
to O
end O
- O
stage O
renal O
disease O
. O
Methods O
Patients O
who O
presented O
with O
accelerated O
hypertension O
, O
renal O
dysfunction O
, O
and O
had O
undergone O
renal O
biopsy O
were O
evaluated O
and O
their O
clinical O
profile O
was O
analyzed O
. O
Those O
who O
became O
dialysis O
dependent O
were O
excluded O
from O
further O
follow O
- O
up O
. O
Study O
outcome O
were O
blood O
pressure O
control O
, O
renal O
functions O
, O
requirement O
of O
renal O
replacement O
and O
mortality O
. O
Results O
Of O
the O
30 O
patients O
evaluated O
, O
age O
at O
presentation O
was O
41.2 O
± O
15.46 O
years O
and O
26 B-STAT
( O
86.7 O
% O
) O
were O
males O
, O
10 B-STAT
( O
33 O
% O
) O
had O
presented O
with O
nonspecific O
complaints O
. O
Mean O
duration O
of O
hypertension O
and O
blood O
pressure O
were O
21.93 O
months O
and O
196 B-STAT
± I-STAT
20.8/129 I-STAT
± O
12.4 O
mmHg O
, O
respectively O
. O
Glomerulonephritis O
and O
hypertensive O
nephrosclerosis O
had O
similar O
characteristics O
except O
proteinuria O
( O
P O
= O
0.04 O
) O
. O
Average O
follow O
- O
up O
( O
n O
= O
25 O
) O
duration O
was O
3.69 O
years O
( O
range O
: O
0.05 O
- O
9.6 O
) O
. O
At O
the O
end O
of O
study O
, O
6 O
were O
dialysis O
dependent O
, O
while O
in O
others O
, O
mean O
e O
- O
GFR O
was O
23.96 O
ml O
/ O
min/1.73 O
m O
2 O
. O
Poor O
renal O
prognosis O
was O
predicted O
by O
glomerulonephritis O
( O
relative O
risk-4.6 O
) O
and O
degree O
of O
interstitial O
fibrosis O
. O
Five O
- O
year O
patient O
and O
renal O
survival O
were O
94.4 O
% O
and O
71.9 O
% O
, O
respectively O
. O
Conclusion O
Accelerated O
hypertension O
occurs B-EPI
among O
patients O
with O
both O
primary O
and O
secondary O
hypertension O
. O
It O
leaves O
permanent O
renal O
sequelae O
. O
Though O
some O
patients O
recover O
renal O
function O
partially O
, O
further O
progression O
is O
rapid O
, O
especially O
among O
those O
with O
chronic O
glomerulonephritis O
. O
Background O
An O
isolated O
coronary O
sinus O
( O
CS O
) O
atrial O
septal O
defect O
( O
ASD O
) O
is O
defined O
as O
a O
CS O
unroofed O
in O
the O
terminal O
portion O
without O
a O
persistent O
left O
superior O
vena O
cava O
or O
other O
anomalies O
. O
This O
defect O
is O
rare O
and O
part O
of O
the O
wide O
spectrum O
of O
unroofed O
CS O
syndrome O
( O
URCS O
) O
. O
Recently O
, O
several O
reports O
have O
described O
this O
finding O
. O
The O
database O
of O
New O
Tokyo O
Hospital O
was O
searched O
to O
determine O
the O
incidence B-EPI
of O
this O
defect O
. O
Additionally O
, O
to O
raise O
awareness O
of O
this O
condition O
, O
the O
findings O
from O
five O
patients O
with O
CS O
ASD O
who O
underwent O
surgical O
repair O
at O
New O
Tokyo O
Hospital O
are O
discussed O
. O
Case O
presentation O
The O
patients O
were O
three O
women O
and O
two O
men O
with O
an O
age O
range O
of O
63 O
- O
77 O
years O
. O
All O
patients O
underwent O
transthoracic O
echocardiography O
and O
computed O
tomography O
, O
and O
one O
underwent O
magnetic O
resonance O
imaging O
. O
In O
two O
patients O
, O
the O
defect O
was O
found O
unexpectedly O
intraoperatively O
; O
left O
- O
to O
- O
right O
shunting O
was O
apparent O
in O
the O
other O
three O
patients O
preoperatively O
. O
The O
pulmonary O
- O
to O
- O
systemic O
blood O
flow O
ratio O
ranged O
from O
1.42 O
to O
3.1 O
following O
cardiac O
catheterization O
, O
and O
oxygen O
saturation O
step O
- O
up O
was O
seen O
on O
the O
right O
side O
of O
the O
heart O
. O
Valvular O
regurgitation O
was O
seen O
in O
4/5 B-STAT
patients O
with O
different O
combinations O
and O
degrees O
of O
mitral O
, O
tricuspid O
, O
and O
aortic O
valve O
involvement O
. O
Right O
atrial O
and O
ventricular O
dilation O
were O
seen O
in O
4/5 B-STAT
patients O
; O
three O
patients O
had O
left O
atrial O
dilation O
. O
Three O
patients O
experienced O
atrial O
fibrillation O
, O
and O
one O
of O
these O
also O
experienced O
paroxysmal O
ventricular O
contractions O
. O
All O
patients O
underwent O
surgical O
repair O
, O
and O
some O
underwent O
multiple O
procedures O
. O
One O
patient O
who O
had O
previously O
undergone O
kidney O
transplantation O
died O
approximately O
1 O
year O
postoperatively O
; O
the O
remaining O
four O
patients O
are O
currently O
experiencing O
good O
activities O
of O
daily O
living O
without O
symptoms O
. O
Conclusions O
CS O
ASD O
( O
Kirklin O
and O
Barratt O
- O
Boyes O
type O
IV O
URCS O
) O
comprised O
1.3 O
% O
of O
adult O
congenital O
heart O
surgeries O
and O
0.07 B-STAT
% I-STAT
of O
adult O
open O
- O
heart O
surgeries O
at O
New O
Tokyo O
Hospital O
from O
1999 O
to O
2019 O
. O
At O
New O
Tokyo O
Hospital O
, O
cardiac O
surgery O
is O
performed O
mainly O
for O
patients O
with O
acquired O
cardiac O
disease O
, O
and O
CS O
ASD O
is O
rare O
. O
Early O
diagnosis O
is O
important O
, O
as O
well O
as O
early O
surgical O
repair O
in O
symptomatic O
patients O
, O
especially O
those O
with O
blood O
access O
shunts O
, O
which O
may O
overload O
the O
heart O
. O
The O
case O
of O
a O
poor O
prognosis O
in O
this O
series O
is O
noteworthy O
, O
as O
similar O
cases O
have O
not O
been O
reported O
previously O
. O
In O
recent O
years O
, O
a O
growing O
body O
of O
research O
has O
shown O
sex O
differences O
in O
the O
prevalence B-EPI
and O
symptomatology O
of O
psychopathologies O
, O
such O
as O
depression O
, O
anxiety O
, O
and O
fear O
- O
related O
disorders O
, O
all O
of O
which O
show O
high O
incidence B-EPI
rates O
in O
early O
life O
. O
This O
has O
highlighted O
the O
importance O
of O
including O
female O
subjects O
in O
animal O
studies O
, O
as O
well O
as O
delineating O
sex O
differences O
in O
neural O
processing O
across O
development O
. O
Of O
particular O
interest O
is O
the O
corticolimbic O
system O
, O
comprising O
the O
hippocampus O
, O
amygdala O
, O
and O
medial O
prefrontal O
cortex O
. O
In O
rodents O
, O
these O
corticolimbic O
regions O
undergo O
dynamic O
changes O
in O
early O
life O
, O
and O
disruption O
to O
their O
normative O
development O
is O
believed O
to O
underlie O
the O
age O
and O
sex O
- O
dependent O
effects O
of O
stress O
on O
affective O
processing O
. O
In O
this O
review O
, O
we O
consolidate O
research O
on O
sex O
differences O
in O
the O
hippocampus O
, O
amygdala O
, O
and O
medial O
prefrontal O
cortex O
across O
early O
development O
. O
First O
, O
we O
briefly O
introduce O
current O
principles O
on O
sexual O
differentiation O
of O
the O
rodent O
brain O
. O
We O
then O
showcase O
corticolimbic O
regional O
sex O
differences O
in O
volume O
, O
morphology O
, O
synaptic O
organization O
, O
cell O
proliferation O
, O
microglia O
, O
and O
GABAergic O
signaling O
, O
and O
explain O
how O
these O
differences O
are O
influenced O
by O
perinatal O
and O
pubertal O
gonadal O
hormones O
. O
In O
compiling O
this O
research O
, O
we O
outline O
evidence O
of O
what O
and O
when O
sex O
differences O
emerge O
in O
the O
developing O
corticolimbic O
system O
, O
and O
illustrate O
how O
temporal O
dynamics O
of O
its O
maturational O
trajectory O
may O
differ O
in O
male O
and O
female O
rodents O
. O
This O
will O
help O
provide O
insight O
into O
potential O
neural O
mechanisms O
underlying O
sex O
- O
specific O
critical O
windows O
for O
stress O
susceptibility O
and O
behavioral O
emergence O
. O
Background O
Pathogenic O
intestinal O
protozoa O
are O
considered O
as O
a O
serious O
public O
health O
problem O
in O
developing O
countries O
. O
This O
study O
aimed O
to O
elucidate O
the O
overall B-EPI
prevalence I-EPI
and O
spatial O
distribution O
of O
three O
common O
human O
pathogenic O
intestinal O
protozoan O
infections O
in O
Iran B-LOC
. O
Methods O
Six O
English O
and O
Persian O
databases O
were O
explored O
for O
published O
papers O
on O
the O
prevalence B-EPI
of O
Entamoeba O
histolytica O
/ O
dispar O
, O
Giardia O
lamblia O
, O
and O
Cryptosporidium O
spp O
. O
in O
the O
general O
population O
of O
Iran B-LOC
from O
2000 O
to O
2015 O
. O
All O
eligible O
data O
were O
collected O
using O
a O
pre O
- O
designed O
data O
extraction O
form O
, O
and O
the O
overall B-EPI
prevalence I-EPI
was O
estimated O
using O
a O
random O
- O
effects O
meta O
- O
analysis O
model O
. O
We O
used O
ArcMap O
for O
mapping O
the O
prevalence B-EPI
of O
the O
studied O
protozoa O
and O
clustering O
analysis O
. O
Results O
Altogether O
, O
118 O
eligible O
papers O
from O
24 O
provinces O
of O
Iran B-LOC
were O
included O
and O
analyzed O
. O
The O
weighted B-EPI
prevalence I-EPI
of O
E. O
histolytica O
/ O
dispar O
, O
G. O
lamblia O
, O
and O
Cryptosporidium O
spp O
. O
infection O
among O
Iranian O
general O
population O
were O
calculated O
1.3 O
% O
( O
95 O
% O
CI O
1.1 O
- O
1.5 O
% O
) O
, O
10.6 O
% O
( O
95 O
% O
CI O
9.6 O
- O
11.5 O
% O
) O
and O
2 O
% O
( O
95 O
% O
CI O
1.5 O
- O
2.5 O
% O
) O
, O
respectively O
. O
Conclusion O
Our O
findings O
indicated O
human O
intestinal O
protozoan O
infections O
caused O
by O
E. O
histolytica O
/ O
dispar O
, O
G. O
lamblia O
, O
and O
Cryptosporidium O
spp O
. O
have O
still O
public O
health O
importance O
in O
some O
parts O
of O
Iran B-LOC
. O
Background O
Down O
syndrome O
is O
the O
most O
common O
chromosomal O
disorder O
at O
birth O
and O
is O
often O
accompanied O
by O
structural O
birth O
defects O
. O
Current O
data O
on O
major O
structural O
defects O
in O
this O
population O
are O
limited O
. O
Methods O
States O
and O
territorial O
population O
- O
based O
surveillance O
programs O
submitted O
data O
on O
identified O
cases O
of O
Down O
syndrome O
and O
identified O
structural O
birth O
defects O
during O
2013 O
- O
2017 O
. O
We O
estimated B-EPI
prevalence I-EPI
by O
program O
type O
and O
maternal O
and O
infant O
characteristics O
. O
Among O
programs O
with O
active O
case O
ascertainment O
, O
we O
estimated O
the O
prevalence B-EPI
of O
birth O
defects O
by O
organ O
system O
and O
for O
specific O
defects O
by O
maternal O
age O
( O
< O
35 O
, O
≥35 O
) O
and O
infant O
sex O
. O
Results O
We O
identified O
13,376 O
cases O
of O
Down O
syndrome O
. O
Prevalence B-EPI
among O
all O
programs O
was O
12.7 B-STAT
per I-STAT
10,000 I-STAT
live I-STAT
births I-STAT
. O
Among O
these O
children O
, O
75 O
% O
had O
at O
least O
one O
reported O
co O
- O
occurring O
birth O
defect O
diagnosis O
code O
. O
Among O
6,210 O
cases O
identified O
by O
active O
programs O
, O
66 O
% O
had O
a O
cardiovascular O
defect O
with O
septal O
defects O
being O
the O
most O
common O
: O
atrial O
( O
32.5 O
% O
) O
, O
ventricular O
( O
20.6 O
% O
) O
, O
and O
atrioventricular O
( O
17.4 O
% O
) O
. O
Defect O
prevalence B-EPI
differed O
by O
infant O
sex O
more O
frequently O
than O
by O
maternal O
age O
. O
For O
example O
, O
atrioventricular O
septal O
defects O
were O
more O
common O
in O
female O
children O
( O
20.1 O
% O
vs. O
15.1 O
% O
) O
while O
limb O
deficiencies O
were O
more O
prevalent B-EPI
in O
male O
children O
( O
0.4 B-STAT
% I-STAT
vs. O
0.1 B-STAT
% I-STAT
) O
. O
Conclusions O
Our O
study O
provides O
updated O
prevalence B-EPI
estimates O
for O
structural O
defects O
, O
including O
rare O
defects O
, O
among O
children O
with O
Down O
syndrome O
using O
one O
of O
the O
largest O
and O
most O
recent O
cohorts O
to O
date O
. O
These O
data O
may O
aid O
clinical O
care O
and O
surveillance O
. O
Georgia B-LOC
uses O
post O
- O
analytical O
tools O
through O
Collaborative O
Laboratory O
Integrated O
Reports O
( O
CLIR O
) O
to O
triage O
abnormal O
newborn O
screening O
( O
NBS O
) O
results O
for O
follow O
- O
up O
. O
Condition O
specific O
tools O
are O
used O
to O
assign O
each O
case O
a O
risk O
level O
, O
which O
is O
used O
to O
guide O
follow O
- O
up O
recommendations O
. O
Follow O
- O
up O
recommendations O
include O
assessment O
by O
the O
child O
's O
primary O
care O
provider O
as O
well O
as O
testing O
, O
either O
a O
repeat O
NBS O
or O
confirmatory O
testing O
. O
Triaging O
abnormal O
cases O
using O
these O
tools O
has O
been O
advantageous O
in O
managing O
the O
workflow O
for O
the O
follow O
- O
up O
team O
, O
as O
well O
as O
prioritizing O
cases O
that O
appropriately O
require O
more O
attention O
and O
resources O
. O
The O
initial O
goal O
in O
utilizing O
these O
tools O
was O
to O
reduce O
the O
amount O
of O
confirmatory O
testing O
, O
particularly O
for O
disorders O
where O
there O
are O
many O
false O
positives O
. O
We O
assessed O
the O
performance O
of O
these O
tools O
retrospectively O
for O
three O
of O
the O
most O
commonly O
detected O
conditions O
by O
tandem O
mass O
spectrometry O
in O
Georgia B-LOC
: O
phenylketonuria O
, O
medium O
chain O
acyl O
- O
CoA O
dehydrogenase O
deficiency O
and O
very O
long O
chain O
dehydrogenase O
deficiency O
. O
The O
post O
- O
analytical O
tools O
appropriately O
assigned O
all O
true O
positive O
cases O
to O
the O
higher O
levels O
of O
follow O
- O
up O
testing O
and O
reduced O
the O
level O
of O
intervention O
for O
a O
significant O
number O
of O
cases O
as O
well O
. O
Based O
on O
the O
experience O
gained O
from O
our O
utilization O
of O
the O
tools O
in O
the O
follow O
- O
up O
program O
, O
we O
are O
well O
situated O
to O
move O
forward O
with O
using O
the O
tools O
in O
a O
more O
prospective O
manner O
, O
and O
reduce O
the O
number O
of O
cases O
that O
will O
be O
reported O
, O
rather O
than O
just O
assigning O
resources O
appropriately O
at O
follow O
- O
up O
. O
Post O
- O
analytical O
tools O
are O
an O
improvement O
over O
trying O
to O
capture O
the O
variation O
in O
the O
newborn O
population O
using O
multiple O
cutoffs O
. O
It O
also O
easily O
identifies O
significant O
abnormalities O
that O
are O
unrelated O
to O
inherited O
disease O
, O
such O
as O
large O
amino O
acid O
elevations O
due O
to O
total O
parenteral O
nutrition O
. O
Aim O
: O
Sentinel O
lymph O
node O
biopsy O
( O
SLNB O
) O
is O
the O
accepted O
approach O
to O
stage O
the O
clinically O
negative O
axilla O
. O
The O
incidence B-EPI
of O
lymphedema O
( O
LE O
) O
after O
SLNB O
is O
about O
5 B-STAT
% I-STAT
. O
We O
hypothesize O
that O
patients O
undergoing O
axillary O
excision O
of O
> O
5 O
lymph O
nodes O
( O
LNs O
) O
are O
at O
increased O
risk O
of O
developing O
LE O
. O
Methods O
and O
Results O
: O
A O
single O
institution O
prospective O
breast O
cancer O
database O
was O
retrospectively O
reviewed O
from O
January O
2013 O
to O
December O
2017 O
, O
to O
identify O
patients O
who O
underwent O
SLNB O
and O
were O
diagnosed O
with O
LE O
. O
Inclusion O
criteria O
was O
( O
1 O
) O
de O
novo O
breast O
cancer O
, O
( O
2 O
) O
SLNB O
in O
clinically O
node O
negative O
patients O
, O
and O
( O
3 O
) O
no O
preoperative O
diagnosis O
LE O
of O
an O
extremity O
. O
Exclusion O
criteria O
was O
history O
of O
axillary O
lymph O
node O
dissection O
. O
Age O
, O
body O
mass O
index O
, O
tumor O
- O
node O
- O
metastasis O
status O
, O
surgery O
type O
, O
neoadjuvant O
or O
adjuvant O
chemotherapy O
, O
radiotherapy O
, O
and O
hormone O
therapy O
were O
analyzed O
. O
Of O
the O
3325 O
patients O
identified O
, O
2940 O
patients O
met O
the O
inclusion O
criteria O
and O
were O
included O
in O
the O
final O
analysis O
. O
Median O
follow O
- O
up O
time O
was O
24 O
months O
. O
Forty O
- O
seven O
( O
2 O
% O
) O
patients O
were O
diagnosed O
with O
LE O
, O
and O
nine O
patients O
( O
19 O
% O
) O
had O
> O
5 O
LNs O
excised O
. O
LE O
was O
diagnosed O
in O
3.7 O
% O
of O
patients O
who O
had O
> O
5 O
LNs O
excised O
versus O
1.4 O
% O
of O
patients O
with O
≤5 O
LNs O
excised O
. O
Incidence B-EPI
of O
LE O
was O
higher O
in O
patients O
with O
> O
5 O
LNs O
excision O
( O
p O
= O
0.006 O
) O
. O
Conclusion O
: O
Our O
study O
showed O
that O
patients O
have O
a O
higher O
likelihood O
of O
developing O
LE O
when O
> O
5 O
LNs O
are O
excised O
. O
Background O
In O
South B-LOC
Korea I-LOC
, O
the O
number O
of O
Q O
fever O
cases O
has O
rapidly O
increased O
since O
2015 O
. O
Therefore O
, O
this O
study O
aimed O
to O
characterize O
the O
epidemiological O
and O
clinical O
features O
of O
Q O
fever O
in O
South B-LOC
Korea I-LOC
between O
2011 O
and O
2017 O
. O
Methods O
/ O
principal O
findings O
We O
analyzed O
the O
epidemiological O
investigations O
and O
reviewed O
the O
medical O
records O
from O
all O
hospitals O
that O
had O
reported O
at O
least O
one O
case O
of O
Q O
fever O
from O
2011 O
to O
2017 O
. O
We O
also O
conducted O
an O
online O
survey O
to O
investigate O
physicians O
' O
awareness O
regarding O
how O
to O
appropriately O
diagnose O
and O
manage O
Q O
fever O
. O
The O
nationwide B-EPI
incidence I-EPI
rate O
of O
Q O
fever O
was O
annually O
0.07 B-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
persons I-STAT
. O
However O
, O
there O
has O
been O
a O
sharp O
increase O
in O
its O
incidence B-EPI
, O
reaching O
up O
to O
0.19 B-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
persons I-STAT
in O
2017 O
. O
Q O
fever O
sporadically O
occurred O
across O
the O
country O
, O
with O
the O
highest O
incidences B-EPI
in O
Chungbuk O
( O
0.53 B-STAT
cases I-STAT
per I-STAT
100,000 B-STAT
persons I-STAT
per I-STAT
year I-STAT
) I-STAT
and O
Chungnam O
( O
0.27 B-STAT
cases I-STAT
per I-STAT
100,000 B-STAT
persons I-STAT
per I-STAT
year I-STAT
) I-STAT
areas O
. O
Patients O
with O
acute O
Q O
fever O
primarily O
presented O
with O
mild O
illnesses O
such O
as O
hepatitis O
( O
64.5 O
% O
) O
and O
isolated O
febrile O
illness O
( O
24.0 O
% O
) O
, O
whereas O
those O
with O
chronic O
Q O
fever O
were O
likely O
to O
undergo O
surgery O
( O
41.2 O
% O
) O
and O
had O
a O
high O
mortality O
rate O
( O
23.5 O
% O
) O
. O
Follow O
- O
up O
for O
6 O
months O
after O
acute O
Q O
fever O
was O
performed O
by O
24.0 O
% O
of O
the O
physician O
respondents O
, O
and O
only O
22.3 O
% O
of O
them O
reported O
that O
clinical O
and O
serological O
evaluations O
were O
required O
after O
acute O
Q O
fever O
diagnosis O
. O
Conclusions O
Q O
fever O
is O
becoming O
an O
endemic O
disease O
in O
the O
midwestern O
area O
of O
South B-LOC
Korea I-LOC
. O
Given O
the O
clinical O
severity O
and O
mortality O
of O
chronic O
Q O
fever O
, O
physicians O
should O
be O
made O
aware O
of O
appropriate O
diagnosis O
and O
management O
strategies O
for O
Q O
fever O
. O
Dyslipidemia O
is O
a O
major O
cause O
of O
cardiovascular O
diseases O
which O
represent O
a O
leading O
cause O
of O
death O
in O
humans O
. O
Diverse O
immune O
cells O
are O
known O
to O
be O
involved O
in O
the O
pathogenesis O
of O
cardiovascular O
diseases O
such O
as O
atherosclerosis O
. O
Conversely O
, O
dyslipidemia O
is O
known O
to O
be O
tightly O
associated O
with O
immune O
disorders O
in O
humans O
, O
as O
evidenced O
by O
a O
higher O
incidence B-EPI
of O
atherosclerosis O
in O
patients O
with O
autoimmune O
diseases O
including O
psoriasis O
, O
rheumatoid O
arthritis O
, O
and O
systemic O
lupus O
erythematosus O
. O
Given O
that O
the O
dyslipidemia O
- O
related O
autoimmune O
diseases O
are O
caused O
by O
autoreactive O
T O
cells O
and O
B O
cells O
, O
dyslipidemia O
seems O
to O
directly O
or O
indirectly O
regulate O
the O
adaptive O
immunity O
. O
Indeed O
, O
accumulating O
evidence O
has O
unveiled O
that O
proatherogenic O
factors O
can O
impact O
the O
differentiation O
and O
function O
of O
CD4 O
+ O
T O
cells O
, O
CD8 O
+ O
T O
cells O
, O
and O
B O
cells O
. O
This O
review O
discusses O
an O
updated O
overview O
on O
the O
regulation O
of O
adaptive O
immunity O
by O
dyslipidemia O
and O
proposes O
a O
potential O
therapeutic O
strategy O
for O
immune O
disorders O
by O
targeting O
lipid O
metabolism O
. O
Neuroendocrine O
tumors O
( O
NETs O
) O
are O
rare O
neoplasms O
, O
with O
an O
estimated O
annual B-EPI
incidence I-EPI
of O
6.9/100 B-STAT
000 O
. O
They O
arise O
from O
cells O
of O
the O
diffuse O
endocrine O
system O
, O
which O
are O
mainly O
dispersed O
throughout O
the O
gastrointestinal O
( O
GI O
) O
, O
pancreatic O
, O
and O
respiratory O
tracts O
. O
The O
incidence B-EPI
of O
GI O
- O
NETs O
has O
recently O
begun O
to O
show O
a O
steady O
increase O
. O
According O
to O
the O
Surveillance O
, O
Epidemiology O
, O
and O
End O
Results O
database O
, O
53 O
% O
of O
patients O
with O
NETs O
present O
with O
localized O
disease O
, O
20 O
% O
with O
locoregional O
disease O
, O
and O
27 O
% O
with O
distant O
metastases O
at O
the O
time O
of O
diagnosis O
. O
Surgery O
is O
the O
mainstay O
for O
the O
treatment O
of O
locoregional O
GI O
- O
NETs O
. O
Endoscopic O
resection O
is O
an O
option O
for O
well O
- O
differentiated O
early O
GI O
- O
NETs O
, O
which O
are O
thought O
to O
very O
rarely O
metastasize O
to O
lymph O
nodes O
. O
A O
lesion O
that O
is O
technically O
difficult O
to O
resect O
via O
endoscopy O
is O
an O
indication O
for O
local O
resection O
( O
partial O
resection O
without O
lymph O
node O
dissection O
) O
. O
GI O
- O
NETs O
with O
possible O
lymph O
node O
metastasis O
is O
an O
indication O
for O
enterectomy O
with O
lymph O
node O
dissection O
. O
For O
NETs O
with O
metastatic O
lesions O
, O
cytoreduction O
surgery O
can O
control O
hormonal O
hypersecretion O
and O
alleviate O
symptoms O
; O
therefore O
, O
cytoreduction O
surgery O
is O
recommended O
. O
The O
indications O
for O
surgery O
vary O
and O
are O
based O
on O
the O
organ O
where O
the O
NET O
arose O
; O
therefore O
, O
an O
understanding O
of O
the O
patient O
's O
clinical O
state O
and O
individualized O
treatment O
that O
is O
based O
on O
the O
characteristics O
of O
the O
patient O
's O
GI O
- O
NET O
is O
needed O
. O
This O
review O
summarizes O
surgical O
treatments O
of O
GI O
- O
NETs O
in O
each O
organ O
. O
Background O
Tuberculosis O
osteomyelitis O
is O
rarely O
seen O
in O
the O
diaphyseal O
bones O
. O
It O
may O
be O
confused O
with O
Brodie O
's O
abscess O
due O
to O
similar O
clinical O
, O
radiological O
and O
laboratory O
findings O
. O
Late O
diagnosis O
of O
the O
disease O
causes O
bone O
destruction O
. O
Tuberculosis O
osteomyelitis O
of O
the O
bone O
is O
a O
rare O
condition O
caused O
by O
the O
Mycobacterium O
tuberculosis O
. O
Its O
incidence B-EPI
has O
increased O
in O
Western O
countries O
in O
recent O
years O
due O
to O
HIV O
infection O
, O
increasing O
elderly O
population O
and O
emerging O
resistant O
strains O
. O
The O
slow O
progress O
of O
tuberculous O
osteomyelitis O
, O
due O
to O
lack O
of O
significant O
elevations O
in O
the O
laboratory O
values O
and O
changes O
in O
the O
radiographic O
appearance O
, O
often O
leads O
to O
confusion O
with O
the O
subtypes O
of O
subacute O
osteomyelitis O
, O
defined O
as O
Brodie O
's O
abscess O
. O
These O
two O
low O
- O
virulence O
clinical O
cases O
often O
lead O
to O
delays O
in O
diagnosis O
and O
progressive O
bone O
destruction O
. O
Case O
presentation O
We O
report O
a O
65 O
- O
year O
- O
old O
male O
patient O
who O
presented O
to O
our O
clinic O
with O
pain O
, O
swelling O
and O
sensitivity O
in O
the O
left O
leg O
. O
Diagnosed O
with O
infection O
in O
the O
tibia O
, O
the O
patient O
had O
undergone O
antibiotherapy O
. O
However O
, O
the O
patient O
's O
symptoms O
were O
not O
resolved O
and O
we O
performed O
bone O
curettage O
and O
cementation O
. O
M. O
tuberculosis O
-specific O
DNA O
was O
detected O
by O
real O
- O
time O
polymerase O
chain O
reaction O
and O
the O
M. O
tuberculosis O
complex O
was O
produced O
from O
the O
perioperative O
samples O
. O
Conclusion O
In O
conclusion O
, O
histopathological O
examination O
and O
polymerase O
chain O
reaction O
are O
essential O
before O
surgery O
of O
subacute O
and O
chronic O
osteomyelitis O
with O
atypical O
clinical O
, O
laboratory O
and O
radiological O
findings O
for O
early O
diagnosis O
and O
accurate O
treatment O
. O
Background O
Many O
studies O
reported O
high O
prevalence B-EPI
of O
antiphospholipid O
antibodies O
( O
aPL O
) O
in O
patients O
with O
COVID-19 O
raising O
questions O
about O
its O
true O
prevalence B-EPI
and O
its O
clinical O
impact O
on O
the O
disease O
course O
. O
Methods O
We O
conducted O
a O
meta O
- O
analysis O
and O
a O
systematic O
review O
to O
examine O
the O
prevalence B-EPI
of O
aPL O
and O
its O
clinical O
impact O
in O
patients O
with O
COVID-19 O
. O
Results O
21 O
studies O
with O
a O
total O
of O
1159 O
patients O
were O
included O
in O
our O
meta O
- O
analysis O
. O
Among O
patients O
hospitalised O
with O
COVID-19 O
, O
the O
pooled B-EPI
prevalence I-EPI
rate O
of O
one O
or O
more O
aPL O
( O
IgM O
or O
IgG O
or O
IgA O
of O
anticardiolipin O
( O
aCL O
) O
or O
anti O
- O
ß2 O
glycoprotein O
( O
anti O
- O
ß2 O
GPI O
) O
or O
antiphosphatidylserine O
/ O
prothrombin O
, O
or O
lupus O
anticoagulant O
( O
LA B-LOC
) O
) O
was O
46.8 O
% O
( O
95 O
% O
CI O
36.1 O
% O
to O
57.8 O
% O
) O
. O
The O
most O
frequent O
type O
of O
aPL O
found O
was O
LA B-LOC
, O
with O
pooled B-EPI
prevalence I-EPI
rate O
of O
50.7 O
% O
( O
95 O
% O
CI O
34.8 O
% O
to O
66.5 O
% O
) O
. O
Critically O
ill O
patients O
with O
COVID-19 O
had O
significantly O
higher O
prevalence B-EPI
of O
aCL O
( O
IgM O
or O
IgG O
) O
( O
28.8 O
% O
vs O
7.10 O
% O
, O
p<0.0001 O
) O
and O
anti O
- O
ß2 O
GPI O
( O
IgM O
or O
IgG O
) O
( O
12.0 O
% O
vs O
5.8 O
% O
, O
p<0.0001 O
) O
as O
compared O
with O
non O
- O
critically O
ill O
patients O
. O
However O
, O
there O
was O
no O
association O
between O
aPL O
positivity O
and O
mean O
levels O
of O
C O
reactive O
protein O
( O
mean O
difference O
was O
32 B-STAT
( O
95 O
% O
CI O
-15 O
to O
79 O
) O
, O
p=0.18 O
) O
, O
D O
- O
dimer O
( O
mean O
difference O
was O
34 B-STAT
( O
95 O
% O
CI O
-194 O
to O
273 O
) O
, O
p=0.77 O
) O
, O
mortality O
( O
1.46 O
( O
95 O
% O
CI O
0.29 O
to O
7.29 O
) O
, O
p=0.65 O
) O
, O
invasive O
ventilation O
( O
1.22 O
( O
95 O
% O
CI O
0.51 O
to O
2.91 O
) O
, O
p=0.65 O
) O
and O
venous O
thromboembolism O
( O
1.38 O
( O
95 O
% O
CI O
0.57 O
to O
3.37 O
) O
, O
p=0.48 O
) O
. O
Conclusions O
aPLs O
were O
detected O
in O
nearly O
half O
of O
patients O
with O
COVID-19 O
, O
and O
higher O
prevalence B-EPI
of O
aPL O
was O
found O
in O
severe O
disease O
. O
However O
, O
there O
was O
no O
association O
between O
aPL O
positivity O
and O
disease O
outcomes O
including O
thrombosis O
, O
invasive O
ventilation O
and O
mortality O
. O
However O
, O
further O
studies O
are O
required O
to O
identify O
the O
clinical O
and O
pathological O
role O
of O
aPL O
in O
COVID-19 O
. O
The O
increasing O
prevalence B-EPI
of O
AF O
in O
a O
growing O
population O
of O
adults O
with O
congenital O
heart O
disease O
( O
CHD O
) O
poses O
new O
challenges O
to O
clinicians O
involved O
in O
the O
management O
of O
these O
patients O
. O
Distinctive O
underlying O
anatomies O
, O
unique O
physiological O
aspects O
, O
a O
high O
diversity O
of O
corrective O
surgeries O
and O
associated O
comorbidities O
can O
complicate O
clinical O
decision O
- O
making O
. O
In O
this O
review O
, O
the O
authors O
provide O
an O
overview O
of O
the O
current O
knowledge O
on O
epidemiology O
and O
pathophysiology O
, O
with O
a O
special O
focus O
on O
the O
differences O
to O
the O
non O
- O
CHD O
population O
and O
the O
clinical O
impact O
of O
AF O
in O
adults O
with O
CHD O
. O
Acute O
and O
long O
- O
term O
management O
strategies O
are O
summarised O
, O
including O
the O
use O
of O
antiarrhythmic O
drugs O
, O
catheter O
or O
surgical O
ablation O
and O
prophylaxis O
of O
thromboembolism O
. O
Finally O
, O
gaps O
of O
knowledge O
and O
potential O
areas O
of O
future O
research O
are O
highlighted O
. O
Background O
Cobalamin O
( O
cbl O
) O
C O
is O
a O
treatable O
rare O
hereditary O
disorder O
of O
cbl O
metabolism O
with O
autosomal O
recessive O
inheritance O
. O
It O
is O
the O
most O
common O
organic O
acidemia O
, O
manifested O
as O
methylmalonic O
academia O
combined O
with O
homocysteinemia O
. O
Early O
screening O
and O
diagnosis O
are O
important O
. O
The O
mutation O
spectrum O
of O
the O
MMACHC O
gene O
causing O
cblC O
varies O
among O
populations O
. O
The O
mutation O
spectrum O
in O
Chinese O
population O
is O
notably O
different O
from O
that O
in O
other O
populations O
. O
Methods O
A O
PCR O
followed O
by O
high O
- O
resolution O
melting O
curve O
analysis O
( O
PCR O
- O
HRM O
) O
method O
covering O
all O
coding O
exons O
of O
MMACHC O
gene O
was O
designed O
to O
verify O
14 O
pathogenic O
MMACHC O
gene O
variants O
found O
in O
patients O
with O
cblC O
, O
including O
all O
common O
mutations O
in O
Chinese O
patients O
with O
cblC. O
Result O
By O
PCR O
- O
HRM O
analysis O
, O
14 O
pathogenic O
variants O
of O
MMACHC O
showed O
distinctly O
different O
melting O
curves O
, O
which O
were O
consistent O
with O
Sanger O
sequencing O
. O
The O
homozygous O
type O
of O
the O
most O
common O
mutation O
c.609 O
G O
> O
A O
( O
p. O
Trp203Ter O
) O
can O
also O
be O
analyzed O
by O
specially O
designed O
PCR O
- O
HRM O
. O
Conclusion O
The O
established O
PCR O
- O
HRM O
method O
for O
screening O
common O
pathogenic O
MMACHC O
variants O
in O
Chinese O
patients O
with O
cblC O
has O
the O
advantages O
of O
high O
accuracy O
, O
high O
throughput O
, O
low O
cost O
, O
and O
high O
speed O
. O
It O
is O
suitable O
for O
the O
large O
- O
sample O
screening O
of O
suspected O
children O
with O
methylmalonic O
acidemia O
and O
carriers O
in O
population O
. O
Purpose O
Kabuki O
syndrome O
( O
KS O
) O
( O
OMIM O
147920 O
and O
300867 O
) O
is O
a O
rare O
genetic O
disorder O
characterized O
by O
specific O
facial O
features O
, O
intellectual O
disability O
, O
and O
various O
malformations O
. O
Immunopathological O
manifestations O
seem O
prevalent B-EPI
and O
increase O
the O
morbimortality O
. O
To O
assess O
the O
frequency O
and O
severity O
of O
the O
manifestations O
, O
we O
measured O
the O
prevalence B-EPI
of O
immunopathological O
manifestations O
as O
well O
as O
genotype O
- O
phenotype O
correlations O
in O
KS B-LOC
individuals O
from O
a O
registry O
. O
Methods O
Data O
were O
for O
177 O
KS O
individuals O
with O
KDM6A O
or O
KMT2D O
pathogenic O
variants O
. O
Questionnaires O
to O
clinicians O
were O
used O
to O
assess O
the O
presence O
of O
immunodeficiency O
and O
autoimmune O
diseases O
both O
on O
a O
clinical O
and O
biological O
basis O
. O
Results O
Overall O
, O
44.1 O
% O
( O
78/177 O
) O
and O
58.2 O
% O
( O
46/79 O
) O
of O
KS B-LOC
individuals O
exhibited O
infection O
susceptibility O
and O
hypogammaglobulinemia O
, O
respectively O
; O
13.6 O
% O
( O
24/177 O
) O
had O
autoimmune O
disease O
( O
AID O
; O
25.6 O
% O
[ O
11/43 O
] O
in O
adults O
) O
, O
5.6 O
% O
( O
10/177 O
) O
with O
≥2 O
AID O
manifestations O
. O
The O
most O
frequent O
AID O
manifestations O
were O
immune O
thrombocytopenic O
purpura O
( O
7.3 O
% O
[ O
13/177 O
] O
) O
and O
autoimmune O
hemolytic O
anemia O
( O
4.0 O
% O
[ O
7/177 O
] O
) O
. O
Among O
nonhematological O
manifestations O
, O
vitiligo O
was O
frequent O
. O
Immune O
thrombocytopenic O
purpura O
was O
frequent O
with O
missense O
versus O
other O
types O
of O
variants O
( O
p O
= O
0.027 O
) O
. O
Conclusion O
The O
high O
prevalence B-EPI
of O
immunopathological O
manifestations O
in O
KS B-LOC
demonstrates O
the O
importance O
of O
systematic O
screening O
and O
efficient O
preventive O
management O
of O
these O
treatable O
and O
sometimes O
life O
- O
threatening O
conditions O
. O
Mandatory O
folic O
acid O
fortification O
in O
the B-LOC
United I-LOC
States I-LOC
corresponded O
with O
a O
decline O
in O
the O
prevalence B-EPI
of O
spina O
bifida O
( O
SB O
) O
. O
The O
aim O
of O
this O
study O
was O
to O
describe O
the O
epidemiologic O
characteristics O
of O
isolated O
versus O
non O
- O
isolated O
SB O
cases O
in O
both O
pre- O
and O
post O
- O
fortification O
periods O
. O
SB O
cases O
in O
the O
Slone O
Epidemiology O
Center O
Birth O
Defects O
Study O
from O
1976 O
to O
2011 O
without O
chromosomal O
anomalies O
and O
syndromes O
were O
included O
. O
A O
maternal O
interview O
, O
conducted O
within O
6 O
months O
of O
delivery O
, O
collected O
information O
on O
demographics O
, O
reproductive O
history O
, O
diet O
, O
and O
supplement O
use O
. O
Daily O
folic O
acid O
intake O
in O
the O
periconceptional O
period O
was O
calculated O
using O
both O
dietary O
and O
supplement O
information O
and O
categorized O
as O
low O
intake O
( O
< O
400 O
µg O
/ O
day O
) O
or O
high O
intake O
( O
≥400 O
µg O
/ O
day O
) O
. O
SB O
cases O
( O
n O
= O
1170 O
) O
were O
classified O
as O
isolated O
( O
80.4 O
% O
) O
or O
non O
- O
isolated O
( O
19.1 O
% O
) O
. O
Non O
- O
isolated O
cases O
were O
further O
divided O
into O
subgroups O
based O
on O
accompanying O
major O
malformations O
( O
midline O
, O
renal O
, O
genital O
, O
heart O
, O
laterality O
) O
. O
Compared O
to O
non O
- O
isolated O
cases O
, O
isolated O
cases O
were O
more O
likely O
to O
be O
white O
, O
non O
- O
Hispanic O
and O
have O
more O
than O
12 O
years O
of O
education O
. O
Cases O
in O
the O
renal O
, O
genital O
, O
and O
heart O
subgroups O
had O
the O
lowest O
proportions O
of O
mothers O
with O
a O
high O
folic O
acid O
intake O
. O
The O
change O
from O
pre- O
to O
post O
- O
fortification O
was O
associated O
with O
a O
decrease O
in O
the O
proportion O
of O
isolated O
cases O
from O
83 O
% O
to O
72 O
% O
, O
though O
in O
both O
periods O
isolated O
cases O
were O
more O
likely O
to O
be O
female O
and O
their O
mothers O
were O
more O
likely O
to O
have O
high O
folic O
acid O
intake O
. O
These O
findings O
highlight O
the O
importance O
of O
separating O
isolated O
and O
non O
- O
isolated O
cases O
in O
etiologic O
research O
of O
SB O
. O
Wilson O
's O
disease O
or O
hepatolenticular O
degeneration O
Abstract O
. O
Wilson O
's O
disease O
, O
or O
hepatolenticular O
degeneration O
, O
is O
a O
rare O
inherited O
disorder O
of O
copper O
metabolism O
. O
The O
most O
common O
clinical O
presentations O
are O
liver O
disease O
and O
/ O
or O
neuro O
- O
psychiatric O
manifestations O
. O
Pathophysiologically O
, O
Wilson O
's O
disease O
is O
caused O
by O
mutations O
in O
the O
ATP7B O
gene O
, O
which O
lead O
to O
defective O
biliary O
excretion O
of O
copper O
and O
subsequent O
accumulation O
of O
copper O
in O
the O
liver O
and O
in O
other O
organs O
. O
Its O
prevalence B-EPI
is O
approximately B-STAT
1:30 I-STAT
000 I-STAT
, I-STAT
however O
its O
penetrance O
, O
clinical O
presentation O
and O
disease O
severity O
vary O
widely O
, O
ranging O
from O
asymptomatic O
elevation O
of O
liver O
enzymes O
to O
cirrhosis O
or O
acute O
liver O
failure O
with O
or O
without O
neuro O
- O
psychiatric O
symptoms O
. O
For O
this O
reason O
, O
Wilson O
's O
disease O
should O
be O
suspected O
and O
ruled O
out O
in O
cases O
of O
indeterminate O
liver O
disease O
or O
neuropsychiatric O
disturbances O
. O
The O
diagnostic O
algorithms O
are O
complex O
and O
involve O
clinical O
tests O
, O
ophthalmologic O
examination O
( O
Kayser O
- O
Fleischer O
rings O
in O
split O
- O
lamp O
examination O
) O
, O
blood O
and O
urine O
tests O
, O
genetic O
testing O
, O
imaging O
and O
histology O
. O
In O
compensated O
liver O
disease O
, O
treatment O
of O
Wilson O
's O
disease O
by O
copper O
depletion O
( O
chelators O
, O
zinc O
) O
is O
usually O
effective O
. O
In O
case O
of O
liver O
failure O
liver O
transplantation O
may O
be O
needed O
, O
which O
corrects O
the O
underlying O
error O
of O
copper O
metabolism O
. O
New O
drugs O
with O
improved O
efficacy O
and O
tolerability O
are O
in O
clinical O
development O
. O
Background O
PURPOSE O
: O
Although O
many O
studies O
have O
investigated O
the O
relationship O
between O
transient O
global O
amnesia O
( O
TGA O
) O
and O
migraine O
, O
to O
date O
, O
no O
meta O
- O
analysis O
has O
confirmed O
the O
existence O
and O
size O
of O
their O
association O
. O
Methodology O
Literature O
search O
involved O
MEDLINE O
, O
EMBASE O
, O
CENTRAL O
and O
PsycINFO B-LOC
. O
Observational O
controlled O
studies O
including O
TGA O
patients O
( O
Caplan O
, O
Hodges O
and O
Warlow O
) O
were O
retrieved O
. O
Quality O
evaluation O
was O
based O
on O
the O
Newcastle B-LOC
- O
Ottawa B-LOC
scale O
. O
The O
prevalence B-EPI
of O
migraine O
was O
compared O
in O
TGA O
patients O
vs. O
healthy O
controls O
( O
HC O
) O
, O
as O
well O
as O
in O
TGA O
against O
TIA O
individuals O
. O
Data O
from O
case O
- O
control O
, O
cross O
- O
sectional O
and O
cohort O
studies O
were O
pooled O
separately O
. O
Results O
Literature O
search O
yielded O
1178 O
articles O
, O
12 O
of O
which O
were O
included O
in O
the O
present O
meta O
- O
analysis O
. O
Results O
from O
case O
- O
control O
( O
ten O
) O
, O
cohort O
( O
one O
) O
and O
cross O
- O
sectional O
( O
one O
) O
studies O
were O
compatible O
with O
an O
association O
between O
TGA O
and O
migraine O
. O
The O
nationwide O
inpatient O
cross O
- O
sectional O
study O
was O
of O
lesser O
value O
due O
to O
its O
inpatient O
orientation O
. O
The O
high O
- O
quality O
, O
population O
- O
based O
, O
retrospective O
cohort O
( O
158,301 B-STAT
participants I-STAT
per I-STAT
group I-STAT
) I-STAT
determined O
a O
higher O
relative O
- O
risk O
( O
RR O
) O
of O
TGA O
for O
migraine O
vs. O
non O
- O
migraine O
individuals O
[ O
RR O
= O
2.48 O
, O
95%confidence O
- O
interval O
( O
95 O
% O
CI O
) O
= O
( O
1.32 O
, O
4.87 O
) O
] O
. O
Sensitivity O
testing O
based O
on O
stricter O
diagnostic O
criteria O
strengthened O
the O
estimated O
association O
[ O
RR O
= O
3.84 O
, O
95 O
% O
CI O
= O
( O
1.57 O
, O
9.38 O
) O
] O
. O
Additionally O
, O
pooled O
data O
from O
eight O
case O
- O
control O
studies O
( O
700 O
TGA O
, O
746 O
HC O
) O
yielded O
similar O
results O
[ O
Odds O
- O
Ratio O
, O
OR O
= O
2.51 O
, O
95 O
% O
CI O
= O
( O
1.85 O
, O
3.41 O
) O
] O
, O
with O
the O
association O
mainly O
driven O
by O
the O
three O
high O
- O
quality O
studies O
, O
rather O
than O
the O
five O
articles O
of O
moderate O
quality O
. O
Finally O
, O
pooled O
findings O
from O
four O
case O
- O
control O
studies O
of O
moderate O
- O
quality O
revealed O
a O
higher O
prevalence B-EPI
of O
migraine O
among O
TGA O
compared O
to O
TIA O
patients O
[ O
OR O
= O
1.82 O
, O
95 O
% O
CI O
= O
( O
1.22 O
, O
2.73 O
) O
] O
. O
Conclusions O
A O
significant O
association O
between O
TGA O
and O
migraine O
was O
established O
. O
The O
underlying O
connecting O
mechanism O
remains O
undetermined O
, O
yet O
. O
Short O
- O
term O
VEEG O
represents O
an O
affordable O
option O
in O
limited O
resources O
environments O
. O
There O
are O
few O
reports O
on O
its O
use O
. O
Its O
diagnostic O
yield O
is O
variable O
( O
7 B-STAT
- O
57 O
% O
) O
and O
can O
be O
related O
to O
the O
differences O
in O
recording O
time O
. O
The O
present O
study O
analyzes O
possible O
predictive O
factors O
to O
support O
the O
indication O
of O
a O
short O
- O
term O
VEEG O
. O
We O
analyzed O
short O
- O
term O
VEEG O
studies O
( O
< O
24 O
h O
) O
throughout O
a O
period O
of O
5 O
years O
( O
2013 O
- O
2017 O
) O
. O
The O
patients O
were O
clustered O
according O
to O
the O
date O
of O
last O
epileptic O
seizure O
and O
the O
frequency O
of O
epileptic O
events O
per O
month O
and O
subcategorized O
depending O
on O
the O
frequency O
found O
. O
Chi O
square O
univariate O
analysis O
was O
performed O
looking O
for O
predictive O
variables O
to O
obtain O
an O
epileptic O
short O
- O
term O
EEG O
. O
A O
multivariate O
logistic O
regression O
analysis O
was O
performed O
with O
statistically O
significant O
variables O
. O
A O
total O
of O
1092 O
VEEG O
were O
analyzed O
from O
832 O
patients O
. O
34.5 B-STAT
% I-STAT
were O
reported O
as O
epileptic O
VEEG O
. O
In O
the O
multivariate O
analysis O
, O
3 O
predictors O
of O
epileptic O
short O
- O
term O
VEEG O
were O
identified O
: O
The O
use O
of O
2 O
or O
more O
antiepileptic O
drugs O
( O
AEDs O
) O
( O
OR O
1.67 O
, O
CI O
1.23 O
- O
2.25 O
, O
p O
= O
0.001 O
) O
, O
the O
presence O
of O
an O
epileptic O
event O
in O
the O
last O
month O
( O
OR O
1.53 O
, O
CI O
1.07 O
- O
2.17 O
, O
p O
= O
0.018 O
) O
and O
daily O
seizures O
( O
OR O
1.84 O
, O
CI O
1.21 O
- O
2.78 O
, O
p O
= O
0.004 O
) O
. O
Six O
- O
month O
seizure O
free O
subjects O
predict O
a O
non O
- O
epileptic O
VEEG O
( O
OR O
0.58 O
, O
CI O
0.30 O
- O
0.89 O
, O
p O
= O
0.013 O
) O
. O
The O
Wiskott O
- O
Aldrich O
syndrome O
( O
WAS O
) O
is O
an O
X O
- O
linked O
disorder O
caused O
by O
mutations O
in O
the O
WAS O
gene O
resulting O
in O
congenital O
thrombocytopenia O
, O
eczema O
, O
recurrent O
infections O
and O
an O
increased O
incidence B-EPI
of O
autoimmune O
diseases O
and O
malignancies O
. O
Without O
curative O
therapies O
, O
affected O
patients O
have O
diminished O
life O
expectancy O
and O
reduced O
quality O
of O
life O
. O
Since O
WAS O
protein O
( O
WASP O
) O
is O
constitutively O
expressed O
only O
in O
hematopoietic O
stem O
cell O
- O
derived O
lineages O
, O
hematopoietic O
stem O
cell O
transplantation O
( O
HSCT O
) O
and O
gene O
therapy O
( O
GT O
) O
are O
well O
suited O
to O
correct O
the O
hematologic O
and O
immunologic O
defects O
. O
Advances O
in O
high O
- O
resolution O
HLA O
typing O
, O
new O
techniques O
to O
prevent O
GvHD O
allowing O
the O
use O
of O
haploidentical O
donors O
, O
and O
the O
introduction O
of O
reduced O
intensity O
conditioning O
regimens O
with O
myeloablative O
features O
have O
increased O
overall O
survival O
( O
OS O
) O
to O
over O
90 B-STAT
% I-STAT
. O
The O
development O
of O
GT O
for O
WAS O
has O
provided O
basic O
knowledge O
into O
vector O
selection O
and O
random O
integration O
of O
various O
viral O
vectors O
into O
the O
genome O
, O
with O
the O
possibility O
of O
inducing O
leukemogenesis O
. O
After O
trials O
and O
errors O
, O
inactivating O
lentiviral O
vectors O
carrying O
the O
WAS O
gene O
were O
successfully O
evaluated O
in O
clinical O
trials O
, O
demonstrating O
cure O
of O
the O
disease O
except O
for O
insufficient O
resolution O
of O
the O
platelet O
defect O
. O
Thus O
, O
50 O
years O
of O
clinical O
evaluation O
, O
genetic O
exploration O
and O
extensive O
clinical O
trials O
, O
a O
lethal O
syndrome O
has O
turned O
into O
a O
curable O
disorder O
. O
Background O
Repeated O
inflammation O
of O
the O
pancreas O
can O
cause O
pancreatitis O
or O
diabetes O
. O
It O
is O
well O
recognized O
that O
the O
organic O
acidemias O
may O
be O
complicated O
by O
pancreatitis O
but O
less O
recognized O
are O
other O
metabolic O
disorders O
in O
which O
pancreatitis O
can O
occur O
. O
This O
study O
shows O
that O
long O
- O
term O
follow O
- O
up O
of O
patients O
with O
various O
metabolic O
disorders O
in O
Korea B-LOC
revealed O
several O
with O
episodes O
of O
isolated O
pancreatitis O
or O
diabetes O
concomitantly O
with O
pancreatitis O
. O
Results O
and O
discussion O
In O
this O
study O
, O
two O
patients O
with O
methylmalonic O
aciduria O
( O
MMA O
) O
, O
two O
with O
propionic O
acidemia O
( O
PPA O
) O
, O
one O
with O
fatty O
acid O
oxidation O
disorder O
( O
FAOD O
) O
, O
and O
one O
with O
hyperornithinemia O
, O
gyrate O
atrophy O
, O
and O
juvenile O
onset O
diabetes O
mellitus O
( O
DM O
) O
were O
clinically O
followed O
for O
up O
to O
10 O
- O
21 O
years O
. O
Two O
Korean O
siblings O
with O
MMA O
showed O
recurrent O
pancreatitis O
from O
the O
age O
of O
15 O
and O
19 O
, O
respectively O
. O
The O
frequency O
of O
admission O
due O
to O
pancreatitis O
was O
up O
to O
11 O
times O
. O
One O
patient O
with O
MMA O
developed O
diabetes O
mellitus O
at O
the O
age O
of O
20 O
. O
The O
other O
patient O
with O
MMA O
developed O
recurrent O
pancreatitis O
at O
4 O
years O
and O
diabetes O
at O
8 O
years O
of O
age O
. O
One O
of O
the O
patients O
with O
PPA O
presented O
with O
diabetic O
ketoacidosis O
. O
The O
other O
PPA O
patient O
died O
of O
cardiac O
arrest O
at O
age O
10 O
. O
The O
patient O
with O
FAOD O
presented O
with O
pancreatitis O
at O
10 O
years O
and O
died O
at O
the O
age O
of O
15 O
years O
due O
to O
cardiac O
arrest O
. O
A O
35 O
- O
year O
- O
old O
woman O
with O
hyperornithinemia O
/ O
gyrate O
atrophy O
was O
diagnosed O
with O
juvenile O
onset O
diabetes O
at O
the O
age O
of O
7 O
years O
. O
No O
pancreatitis O
occurred O
during O
the O
follow O
- O
up O
period O
. O
Conclusions O
We O
conclude O
that O
various O
metabolic O
disorders O
can O
trigger O
acute O
or O
chronic O
pancreatitis O
. O
Proper O
and O
prompt O
multidisciplinary O
management O
of O
metabolic O
derangement O
is O
crucial O
for O
preventing O
pancreatic O
damage O
. O
Further O
clinical O
and O
investigational O
studies O
are O
required O
to O
elucidate O
the O
pathogenesis O
of O
pancreatitis O
and O
diabetes O
mellitus O
in O
patients O
with O
inborn O
errors O
in O
metabolism O
. O
Background O
Reported O
birth O
prevalences B-EPI
of O
congenital O
limb O
defects O
( O
CLD O
) O
vary O
between O
countries O
: O
from O
13/10,000 B-STAT
in O
Finland B-LOC
for O
the O
period O
1964 O
- O
1977 O
to I-STAT
30.4/10,000 I-STAT
births I-STAT
in O
Scotland B-LOC
from O
1964 O
- O
1968 O
. O
Epidemiological O
studies O
permit O
the O
timely O
detection O
of O
trends O
in O
CLD O
and O
of O
associations O
with O
other O
birth O
defects O
. O
The O
aim O
of O
this O
study O
is O
to O
describe O
the O
birth O
prevalence B-EPI
of O
CLD O
in O
the O
northern O
Netherlands B-LOC
. O
Methods O
In O
a O
population O
- O
based O
, O
epidemiological O
study O
we O
investigated O
the O
birth O
prevalences B-EPI
of O
CLD O
for O
1981 O
- O
2010 O
. O
Data O
were O
collected O
by O
the O
European O
Surveillance O
of O
Congenital O
Anomalies O
in O
the O
northern O
Netherlands B-LOC
( O
EUROCAT O
- O
NNL O
) O
. O
We O
excluded O
malpositions O
, O
club O
foot O
, O
and O
dislocation O
/ O
dysplasia O
of O
hips O
or O
knees O
. O
Trends O
were O
analysed O
for O
the O
19 O
- O
year O
period O
1992 O
- O
2010 O
using O
χ² O
tests O
, O
as O
well O
as O
CLD O
association O
with O
anomalies O
affecting O
other O
organs O
. O
Results O
The O
birth O
prevalence B-EPI
of O
CLD O
was O
21.1/10,000 B-STAT
births I-STAT
for O
1981 O
- O
2010 O
. O
There O
was O
an O
overall O
decrease O
in O
non O
- O
syndromic O
limb O
defects O
( O
P O
= O
0.023 O
) O
caused O
by O
a O
decrease O
in O
the O
prevalence B-EPI
of O
non O
- O
syndromic O
syndactyly O
( O
P O
< O
0.01 O
) O
in O
1992 O
- O
2010 O
. O
Of O
1,048 O
children O
with O
CLD O
, O
55 O
% O
were O
males O
, O
57 O
% O
had O
isolated O
defects O
, O
13 O
% O
had O
multiple O
congenital O
anomalies O
( O
MCA O
) O
, O
and O
30 O
% O
had O
a O
recognised O
syndrome O
. O
The O
upper O
: O
lower O
limb O
ratio O
was O
2:1 O
, O
and O
the O
left O
: O
right O
side O
ratio O
was O
1.2:1 O
. O
Cardiovascular O
and O
urinary O
tract O
anomalies O
were O
common O
in O
combination O
with O
CLD O
( O
37 O
% O
and O
25 O
% O
of O
cases O
with O
MCA O
) O
. O
Digestive O
- O
tract O
anomalies O
were O
significantly O
associated O
with O
CLD O
( O
P O
= O
0.016 O
) O
. O
Conclusions O
The O
birth O
prevalence B-EPI
of O
CLD O
in O
the O
northern O
Netherlands B-LOC
was O
21.1/10,000 B-STAT
births I-STAT
. O
The O
birth O
prevalence B-EPI
of O
non O
- O
syndromic O
syndactyly O
dropped O
from O
5.2/10,000 B-STAT
to I-STAT
1.1/10,000 I-STAT
in O
1992 O
- O
2010 O
. O
This O
study O
is O
to O
describe O
current O
incidence B-EPI
of O
childhood O
clear O
cell O
sarcoma O
of O
kidney O
( O
CCSK O
) O
and O
to O
investigate O
the O
present O
survival O
of O
this O
cancer O
. O
Surveillance O
, O
Epidemiology O
, O
and O
End O
Result O
( O
SEER O
) O
data O
was O
used O
to O
identify O
children O
with O
CCSK O
and O
Wilms O
tumor O
( O
WT O
) O
aged O
0 O
- O
19 O
years O
in O
the O
US B-LOC
. O
Age O
- O
adjusted O
incidences B-EPI
were O
estimated O
over O
the O
decades O
. O
Age- O
and O
sex O
- O
specific O
epidemiology O
was O
also O
presented O
. O
Propensity O
score O
matching O
was O
used O
to O
balance O
features O
of O
CCSK O
and O
WT O
cases O
. O
Log O
rank O
test O
was O
used O
to O
compare O
survivals O
and O
Cox O
regression O
was O
used O
to O
evaluate O
independent O
effects O
of O
factors O
. O
The O
present O
age O
- O
adjusted O
incidence B-EPI
of O
childhood O
CCSK O
was O
0.205 B-STAT
per I-STAT
million I-STAT
, I-STAT
which O
remained O
stable O
for O
years O
and O
ranked O
third O
in O
all O
pediatric O
renal O
tumors O
. O
The O
incidence B-EPI
rate O
ratios O
for O
boy O
and O
age O
under O
4 O
were O
3 O
and O
21 O
, O
respectively O
. O
The O
current O
5 O
- O
year O
overall O
survival O
( O
OS O
) O
rate O
for O
CCSK O
was O
87 O
% O
, O
which O
is O
not O
evidently O
inferior O
to O
that O
for O
WT O
( O
90 O
% O
) O
; O
however O
the O
outcome O
of O
CCSK O
was O
significantly O
poorer O
if O
both O
groups O
were O
well O
- O
balanced O
( O
OS O
rate O
was O
86 B-STAT
vs. O
95 O
% O
) O
. O
Early O
year O
of O
diagnosis O
and O
distant O
metastasis O
were O
independent O
survival O
factors O
. O
In O
conclusion O
, O
occurrence B-EPI
of O
CCSK O
remains O
stable O
over O
the O
years O
, O
with O
an O
age O
- O
adjusted O
incidence B-EPI
of O
0.205 B-STAT
per I-STAT
million I-STAT
. O
Boy O
and O
age O
under O
4 O
are O
risk O
factors O
for O
tumor O
development O
. O
CCSK O
currently O
has O
a O
favorable O
outcome O
but O
its O
nature O
may O
be O
more O
aggressive O
than O
common O
kidney O
tumor O
, O
which O
in O
turn O
proves O
efficacy O
of O
modern O
treatment O
. O
Background O
Pierre O
Robin O
sequence O
( O
PRS O
) O
is O
a O
rare O
congenital O
anomaly O
. O
Respiratory O
disorders O
and O
feeding O
difficulties O
represent O
the O
main O
burden O
. O
Objective O
The O
aim O
of O
this O
study O
was O
to O
investigate O
the O
epidemiology O
of O
PRS O
using O
a O
cohort O
of O
cases O
from O
EUROCAT O
, O
the O
European O
network O
of O
population O
- O
based O
registries O
of O
congenital O
anomalies O
. O
Methods O
We O
analysed O
cases O
of O
PRS O
born O
in O
the O
period O
1998 O
- O
2017 O
collected O
by O
29 O
population O
- O
based O
congenital O
anomaly O
registries O
in O
17 O
different O
countries O
. O
We O
calculated O
prevalence B-EPI
estimates O
, O
prenatal O
detection O
rate O
, O
survival O
up O
to O
1 O
week O
, O
and O
proportions O
of O
associated O
anomalies O
. O
The O
effect O
of O
maternal O
age O
was O
tested O
using O
a O
Poisson O
regression O
model O
. O
Results O
Out O
of O
11 O
669 O
155 O
surveyed O
births O
, O
a O
total O
of O
1294 O
cases O
of O
PRS O
were O
identified O
. O
The O
estimate O
of O
the O
overall B-EPI
prevalence I-EPI
was O
12.0 B-STAT
per I-STAT
100 I-STAT
000 I-STAT
births I-STAT
( O
95 O
% O
CI O
9.9 O
, O
14.5 O
) O
. O
There O
was O
a O
total O
of O
882 B-STAT
( O
68.2 O
% O
) O
isolated O
cases O
, O
and O
the O
prevalence B-EPI
was O
7.8 B-STAT
per I-STAT
100 I-STAT
000 I-STAT
births I-STAT
( O
95 O
% O
CI O
6.7 O
, O
9.2 O
) O
. O
A O
total O
of O
250 O
cases O
( O
19.3 O
% O
) O
were O
associated O
with O
other O
structural O
congenital O
anomalies O
, O
77 O
cases O
( O
6.0 O
% O
) O
were O
associated O
with O
chromosomal O
anomalies O
and O
77 B-STAT
( O
6.0 O
% O
) O
with O
genetic O
syndromes O
. O
The O
prenatal O
detection O
rate O
in O
isolated O
cases O
was O
12.0 O
% O
( O
95 O
% O
CI O
9.8 O
, O
14.5 O
) O
and O
increased B-STAT
to O
16.0 O
% O
( O
95 O
% O
CI O
12.7 O
, O
19.7 O
) O
in O
the O
sub O
- O
period O
2008 O
- O
2017 O
. O
The O
prevalence B-EPI
rate O
ratio O
of O
non O
- O
chromosomal O
cases O
with O
maternal O
age O
≥35 O
was O
higher O
than O
in O
cases O
with O
maternal O
age O
< O
25 O
for O
total O
( O
PRR O
1.26 O
, O
95 O
% O
CI O
1.05 O
, O
1.51 O
) O
and O
isolated O
cases O
( O
PRR O
1.33 O
, O
95 O
% O
CI O
1.00 O
, O
1.64 O
) O
. O
Survival O
of O
chromosomal O
cases O
( O
94.2 O
% O
) O
and O
multiple O
anomaly O
cases O
( O
95.3 O
% O
) O
were O
lower O
than O
survival O
of O
isolated O
cases O
( O
99.4 O
% O
) O
. O
Conclusions O
This O
epidemiological O
study O
using O
a O
large O
series O
of O
cases O
of O
PRS O
provides O
insights O
into O
the O
epidemiological O
profile O
of O
PRS O
in O
Europe B-LOC
. O
We O
observed O
an O
association O
with O
higher O
maternal O
age O
, O
but O
further O
investigations O
are O
needed O
to O
test O
potential O
risk O
factors O
for O
PRS O
. O
Constitutional O
ring O
chromosomes O
can O
be O
found O
for O
all O
human O
chromosomes O
and O
are O
very O
rare O
chromosomal O
abnormalities O
. O
A O
complete O
ring O
chromosome O
without O
loss O
of O
genetic O
material O
results O
from O
fusion O
of O
subtelomeric O
regions O
or O
telomere O
- O
telomere O
fusion O
. O
In O
cases O
of O
complete O
ring O
chromosome O
, O
an O
increased O
incidence B-EPI
of O
severe O
growth O
failure O
with O
no O
or O
only O
minor O
anomalies O
has O
been O
observed O
and O
attributed O
to O
ring O
syndrome O
. O
Ring O
syndrome O
is O
thought O
to O
be O
caused O
by O
O
dynamic O
mosaicism O
O
due O
to O
ring O
instability O
. O
We O
report O
a O
6 O
- O
year O
- O
old O
boy O
with O
de O
novo O
ring O
chromosome O
4 O
and O
typical O
characteristics O
of O
the O
ring O
syndrome O
, O
namely O
, O
proportionate O
severe O
growth O
failure O
, O
microcephaly O
, O
and O
minor O
anomalies O
. O
Cytogenetic O
studies O
showed O
complete O
ring O
chromosome O
4 O
with O
mitotic O
instability O
. O
Microarray O
gave O
normal O
results O
, O
thus O
excluding O
the O
loss O
of O
detectable O
genetic O
material O
. O
The O
literature O
of O
complete O
ring O
chromosome O
4 O
is O
reviewed O
. O
Our O
case O
report O
supports O
the O
theory O
of O
ring O
syndrome O
. O
No O
studies O
about O
the O
effects O
and O
possible O
side O
effects O
of O
growth O
hormone O
therapy O
on O
patients O
with O
ring O
chromosomes O
have O
yet O
been O
published O
. O
We O
suggest O
that O
cytogenetic O
monitoring O
of O
the O
rate O
of O
secondary O
aberrations O
in O
patients O
with O
ring O
chromosome O
undergoing O
growth O
hormone O
therapy O
might O
be O
feasible O
. O
Since O
the O
diagnosis O
would O
have O
been O
missed O
by O
molecular O
karyotyping O
, O
our O
case O
report O
underlines O
the O
continuing O
role O
of O
classical O
cytogenetics O
for O
the O
evaluation O
of O
structural O
chromosomal O
abnormalities O
in O
patients O
with O
mental O
and/or O
physical O
anomalies O
. O
Standard O
karyotyping O
is O
still O
indispensable O
and O
should O
have O
an O
ongoing O
role O
as O
first O
- O
tier O
analysis O
together O
with O
molecular O
karyotyping O
. O
© O
2017 O
Wiley O
Periodicals O
, O
Inc. O
Congenital O
adrenal O
hyperplasia O
is O
the O
most O
common O
cause O
of O
ambiguous O
genitalia O
worldwide B-LOC
, O
with O
an O
incidence B-EPI
of O
1 O
in O
15,000 O
live O
births O
. O
The O
most O
frequently O
- O
occurring O
subtype O
, O
21 O
- O
hydroxylase O
deficiency O
, O
results O
in O
diminished O
production O
of O
aldosterone O
and O
cortisol O
as O
well O
as O
increased O
androgen O
secretion O
. O
Previous O
studies O
have O
reported O
a O
relationship O
between O
ovarian O
cyst O
formation O
and O
adrenal O
androgen O
excess O
; O
nevertheless O
, O
neonatal O
large O
ovarian O
cysts O
have O
rarely O
been O
reported O
in O
newborns O
with O
congenital O
adrenal O
hyperplasia O
. O
Herein O
, O
we O
present O
the O
unique O
case O
of O
a O
neonate O
with O
classical O
21 O
- O
hydroxylase O
deficiency O
who O
underwent O
surgery O
for O
a O
huge O
unilateral O
solitary O
ovarian O
follicular O
cyst O
on O
the O
seventh O
postnatal O
day O
. O
Possible O
mechanisms O
by O
which O
androgen O
excess O
may O
cause O
ovarian O
cyst O
formation O
are O
also O
discussed O
. O
Objectives O
In O
this O
international O
study O
, O
we O
aimed O
to O
investigate O
the O
opinions O
of O
physicians O
dealing O
with O
patients O
with O
functional O
seizures O
( O
FS O
) O
worldwide B-LOC
on O
working O
restrictions O
and O
disability O
benefits O
eligibility O
. O
Methods O
International O
online O
survey O
of O
neurologists O
/ O
mental O
health O
professionals O
from O
Argentina B-LOC
, O
Venezuela B-LOC
, O
Colombia B-LOC
, O
Italy B-LOC
, O
France B-LOC
, O
Iran B-LOC
, O
Iraq B-LOC
, O
United B-LOC
Arab I-LOC
Emirates I-LOC
( O
UAE O
) O
, O
Qatar B-LOC
, O
Saudi B-LOC
Arabia I-LOC
, O
Georgia B-LOC
, O
and O
Russia B-LOC
. O
Results O
Six O
hundred O
and O
twenty O
- O
seven O
physicians O
from O
12 O
countries O
participated O
in O
the O
study O
. O
Working O
as O
a O
neurologist O
was O
a O
predictor O
to O
think O
that O
patients O
with O
FS O
should O
not O
be O
counseled O
to O
avoid O
performing O
all O
jobs O
or O
professions O
as O
long O
as O
they O
have O
active O
disease O
( O
OR O
: O
0.46 O
; O
95 O
% O
CI O
: O
0.30 O
to O
0.68 O
; O
p O
< O
0.001 O
) O
. O
Having O
managed O
more O
than O
200 O
patients O
was O
associated O
with O
the O
opinion O
that O
patients O
should O
not O
be O
counseled O
to O
avoid O
performing O
any O
type O
of O
work O
( O
OR O
: O
2.17 O
; O
95 O
% O
CI O
: O
1.02 O
to O
4.59 O
; O
p O
= O
0.043 O
) O
. O
Working O
as O
a O
psychiatrist O
/ O
psychologist O
was O
associated O
with O
the O
idea O
that O
patients O
with O
FS O
should O
be O
qualified O
for O
disability O
benefits O
( O
OR O
: O
1.97 O
; O
95 O
% O
CI O
: O
1.21 O
- O
3.21 O
; O
p O
= O
0.006 O
) O
, O
and O
receive O
these O
benefits O
lifelong O
( O
OR O
: O
0.43 O
; O
95 O
% O
CI O
: O
0.22 O
- O
0.84 O
; O
p O
= O
0.014 O
) O
. O
Conclusion O
Neurologists O
and O
mental O
health O
professionals O
have O
different O
attitudes O
and O
opinions O
toward O
working O
restrictions O
and O
disability O
benefits O
for O
patients O
with O
FS O
. O
Further O
studies O
should O
investigate O
the O
reasons O
for O
these O
differences O
, O
and O
propose O
solutions O
to O
avoid O
discrimination O
and O
unequal O
access O
to O
employment O
and O
disability O
benefits O
. O
Exstrophy O
of O
the O
bladder O
is O
a O
rare O
congenital O
anomaly O
with O
an O
incidence B-EPI
of O
about O
1 B-STAT
per I-STAT
50,000 I-STAT
newborns I-STAT
. O
The O
malignant O
potential O
of O
the O
exstrophied O
bladder O
mucosa O
is O
well O
known O
; O
95 O
% O
are O
adenocarcinomas O
, O
and O
3 O
% O
to O
5 O
% O
are O
squamous O
cell O
carcinomas O
. O
Most O
of O
the O
malignant O
tumors O
( O
60 O
% O
) O
associated O
with O
an O
exstrophy O
of O
the O
bladder O
occur O
during O
the O
fourth O
and O
fifth O
decades O
of O
life O
. O
Of O
the O
remaining O
, O
about O
20 O
% O
each O
occur O
after O
60 O
years O
and O
before O
40 O
years O
. O
Here O
we O
present O
a O
case O
in O
which O
squamous O
cell O
carcinoma O
developed O
in O
an O
unrepaired O
exstrophy O
of O
the O
bladder O
. O
We O
present O
the O
management O
of O
the O
case O
and O
a O
brief O
review O
of O
the O
literature O
. O
Pallister O
- O
Hall O
syndrome O
( O
PHS O
) O
is O
an O
extremely O
rare O
syndrome O
of O
unknown B-STAT
prevalence B-EPI
with O
autosomal O
dominant O
inheritance O
due O
to O
GLI3 O
gene O
mutations O
classically O
characterized O
by O
the O
presence O
of O
a O
hypothalamic O
hamartoma O
and O
polydactyly O
. O
Additional O
diagnostic O
criteria O
include O
bifid O
epiglottis O
, O
imperforate O
anus O
, O
small O
nails O
, O
hypopituitarism O
, O
growth O
hormone O
deficiency O
, O
and O
genital O
hypoplasia O
. O
It O
is O
typically O
diagnosed O
in O
infancy O
and O
early O
childhood O
, O
presenting O
with O
seizures O
and/or O
precocious O
puberty O
due O
to O
the O
hypothalamic O
hamartoma O
, O
and O
with O
limb O
anomalies O
due O
to O
central O
polydactyly O
. O
Our O
patient O
had O
presented O
with O
polysyndactyly O
at O
birth O
. O
However O
, O
as O
this O
is O
not O
uncommon O
in O
infants O
and O
is O
usually O
as O
part O
of O
the O
sporadic O
, O
isolated O
form O
of O
polydactyly O
, O
no O
further O
work O
up O
was O
done O
. O
He O
then O
presented O
at O
age O
16 O
years O
with O
a O
headache O
and O
subjective O
visual O
changes O
, O
with O
brain O
imaging O
revealing O
a O
hypothalamic O
hamartoma O
. O
He O
did O
not O
have O
a O
history O
of O
seizures O
or O
central O
precocious O
puberty O
. O
Genotyping O
revealed O
a O
pathogenic O
variant O
affecting O
the O
GLI3 O
gene O
. O
We O
encourage O
all O
clinicians O
to O
consider O
PHS O
or O
an O
associated O
syndrome O
with O
a O
clinical O
finding O
of O
polydactyly O
. O
Further O
, O
as O
the O
natural O
history O
continues O
to O
reveal O
itself O
, O
this O
patient O
's O
presentation O
provides O
important O
new O
data O
to O
the O
broad O
phenotypic O
spectrum O
of O
PHS O
. O
The O
genetic O
basis O
of O
Japanese O
autosomal O
recessive O
retinitis O
pigmentosa O
( O
ARRP O
) O
remains O
largely O
unknown O
. O
Herein O
, O
we O
applied O
a O
2 O
- O
step O
genome O
- O
wide O
association O
study O
( O
GWAS O
) O
in O
640 O
Japanese O
patients O
. O
Meta O
- O
GWAS O
identified O
three O
independent O
peaks O
at O
P O
< O
5.0 O
× O
10 O
-8 O
, O
all O
within O
the O
major O
ARRP O
gene O
EYS O
. O
Two O
of O
the O
three O
were O
each O
in O
linkage O
disequilibrium O
with O
a O
different O
low O
frequency O
variant O
( O
allele O
frequency O
< O
0.05 O
) O
; O
a O
known O
founder O
Mendelian O
mutation O
( O
c.4957dupA O
, O
p. O
S1653Kfs*2 O
) O
and O
a O
non O
- O
synonymous O
variant O
( O
c.2528 O
G O
> O
A O
, O
p. O
G843E O
) O
of O
unknown O
significance O
. O
mRNA O
harboring O
c.2528 O
G O
> O
A O
failed O
to O
restore O
rhodopsin O
mislocalization O
induced O
by O
morpholino O
- O
mediated O
knockdown O
of O
eys O
in O
zebrafish O
, O
consistent O
with O
the O
variant O
being O
pathogenic O
. O
c.2528 O
G O
> O
A O
solved O
an O
additional O
7.0 O
% O
of O
Japanese O
ARRP O
cases O
. O
The O
third O
peak O
was O
in O
linkage O
disequilibrium O
with O
a O
common O
non O
- O
synonymous O
variant O
( O
c.7666 O
A O
> O
T O
, O
p. O
S2556C O
) O
, O
possibly O
representing O
an O
unreported O
disease O
- O
susceptibility O
signal O
. O
GWAS O
successfully O
unraveled O
genetic O
causes O
of O
a O
rare O
monogenic O
disorder O
and O
identified O
a O
high O
frequency O
variant O
potentially O
linked O
to O
development O
of O
local O
genome O
therapeutics O
. O
West B-LOC
Nile I-LOC
virus O
( O
WNV O
) O
is O
a O
zoonotic O
mosquito O
- O
borne O
flavivirus O
that O
is O
harbored O
and O
amplified O
by O
wild O
birds O
via O
the O
enzootic O
transmission O
cycle O
. O
Wide O
range O
of O
hosts O
are O
found O
to O
be O
susceptible O
to O
WNV O
infection O
including O
mammals O
, O
amphibians O
and O
reptiles O
across O
the O
world O
. O
Several O
studies O
have O
demonstrated O
that O
WNV O
was O
present O
in O
the O
Malaysian O
Orang O
Asli O
and O
captive O
birds O
. O
However O
, O
no O
data O
are O
available O
on O
the O
WNV O
prevalence B-EPI
in O
wild O
birds O
found O
in O
Malaysia B-LOC
. O
Therefore O
this O
study O
was O
conducted O
to O
determine O
the O
serological O
and O
molecular O
prevalence B-EPI
of O
WNV O
in O
wild O
birds O
in O
selected O
areas O
in O
the B-LOC
West I-LOC
Coast I-LOC
of O
Peninsular O
Malaysia B-LOC
. O
Two O
types O
of O
wild O
birds O
were O
screened O
, O
namely O
migratory O
and O
resident O
birds O
in O
order O
to O
explore O
any O
possibility O
of O
WNV O
transmission O
from O
the O
migratory O
birds O
to O
the O
resident O
birds O
. O
Thus O
, O
a O
cross O
- O
sectional O
study O
was O
conducted O
at O
the O
migratory O
birds O
sanctuary O
located O
in O
Kuala B-LOC
Gula I-LOC
, O
Perak B-LOC
and O
Kapar B-LOC
, O
Selangor B-LOC
by O
catching O
163 O
migratory O
birds O
, O
and O
97 O
resident O
birds O
from O
Kuala B-LOC
Gula I-LOC
and O
Parit O
Buntar O
, O
Perak B-LOC
at O
different O
time O
between O
2016 O
and O
2017 O
( O
Total O
, O
n O
= O
260 O
) O
. O
Blood O
and O
oropharyngeal O
swabs O
were O
collected O
for O
serological O
and O
molecular O
analysis O
, O
respectively O
. O
Serum O
were O
screened O
for O
WNV O
antibodies O
using O
a O
commercial O
competitive O
ELISA O
( O
c O
- O
ELISA O
) O
( O
ID O
Screen O
® O
West O
Nile O
Competition O
Multi O
- O
species O
ELISA O
, O
ID O
VET O
, O
Montpellier B-LOC
, O
France B-LOC
) O
and O
cross O
- O
reactivity O
towards O
Japanese O
Encephalitis O
virus O
( O
JEV O
) O
was O
also O
carried O
out O
using O
the O
JEV O
- O
double O
antigen O
sandwich O
( O
DAS O
) O
ELISA O
. O
Oropharyngeal O
swabs O
were O
subjected O
to O
one O
- O
step O
RT O
- O
PCR O
to O
detect O
WNV O
RNA O
, O
in O
which O
positive O
reactions O
were O
subsequently O
sequenced O
. O
WNV O
seropositive O
rate O
of O
18.71 O
% O
( O
29/155 O
) O
at O
95 O
% O
CI O
( O
0.131 O
to O
0.260 O
) O
and O
molecular O
prevalence B-EPI
of O
15.2 O
% O
( O
16/105 O
) O
at O
95 O
% O
CI O
( O
0.092 O
to O
0.239 O
) O
were O
demonstrated O
in O
migratory O
and O
resident O
wild O
birds O
found O
in O
West B-LOC
Coast I-LOC
Malaysia B-LOC
. O
Phylogenetic O
analyses O
of O
the O
16 O
WNV O
isolates O
found O
in O
this O
study O
revealed O
that O
the O
local O
strains O
have O
99 O
% O
similarity O
to O
the O
strains O
from O
South B-LOC
Africa I-LOC
and O
were O
clustered O
under O
lineage O
2 O
. O
Evidence O
of O
WNV O
infection O
in O
resident O
and O
migratory O
birds O
were O
demonstrated O
in O
this O
study O
. O
As O
a O
summary O
, O
intervention O
between O
migratory O
birds O
, O
resident O
birds O
and O
mosquitoes O
might O
cause O
the O
introduction O
and O
maintenance O
of O
WNV O
in O
Malaysia B-LOC
, O
however O
the O
assumption O
could O
be O
further O
proven O
by O
studying O
the O
infection O
dynamics O
in O
the O
mosquitoes O
present O
in O
the O
studied O
areas O
. O
Craniosynostosis O
is O
a O
heterogeneous O
condition O
caused O
by O
the O
premature O
fusion O
of O
cranial O
sutures O
, O
occurring O
mostly O
as O
an O
isolated O
anomaly O
. O
Pathogenesis O
of O
non O
- O
syndromic O
forms O
of O
craniosynostosis O
is O
largely O
unknown O
. O
In O
about O
15 O
- O
30 O
% O
of O
cases O
craniosynostosis O
occurs B-EPI
in O
association O
with O
other O
physical O
anomalies O
and O
it O
is O
referred O
to O
as O
syndromic O
craniosynostosis O
. O
Syndromic O
forms O
of O
craniosynostosis O
arise O
from O
mutations O
in O
genes O
belonging O
to O
the O
Fibroblast O
Growth O
Factor O
Receptor O
( O
FGFR O
) O
family O
and O
the O
interconnected O
molecular O
pathways O
in O
most O
cases O
. O
However O
it O
can O
occur O
in O
association O
with O
other O
gene O
variants O
and O
with O
a O
variety O
of O
chromosome O
abnormalities O
as O
well O
, O
usually O
in O
association O
with O
intellectual O
disability O
( O
ID O
) O
and O
additional O
physical O
anomalies O
. O
Evaluating O
the O
molecular O
properties O
of O
the O
genes O
undergoing O
intragenic O
mutations O
or O
copy O
number O
variations O
( O
CNVs O
) O
along O
with O
prevalence B-EPI
of O
craniosynostosis O
in O
different O
conditions O
and O
animal O
models O
if O
available O
, O
we O
made O
an O
attempt O
to O
define O
two O
distinct O
groups O
of O
unusual O
syndromic O
craniosynostosis O
, O
which O
can O
reflect O
direct O
effects O
of O
emerging O
new O
candidate O
genes O
with O
roles O
in O
suture O
homeostasis O
or O
a O
non O
- O
specific O
phenotypic O
manifestation O
of O
pleiotropic O
genes O
, O
respectively O
. O
RASopathies O
and O
9p23p22.3 O
deletions O
are O
reviewed O
as O
examples O
of O
conditions O
in O
the O
first O
group O
. O
In O
particular O
, O
we O
found O
that O
craniosynostosis O
is O
a O
relatively O
common O
component O
manifestation O
of O
cardio O
- O
facio O
- O
cutaneous O
( O
CFC O
) O
syndrome O
. O
Chromatinopathies O
and O
neurocristopathies O
are O
presented O
as O
examples O
of O
conditions O
in O
the O
second O
group O
. O
We O
observed O
that O
craniosynostosis O
is O
uncommon O
on O
average O
in O
these O
conditions O
. O
It O
was O
randomly O
associated O
with O
Kabuki O
, O
Koolen O
- O
de O
Vries O
/ O
KANSL1 O
haploinsufficiency O
and O
Mowat O
- O
Wilson O
syndromes O
and O
in O
KAT6B B-LOC
- O
related O
disorders O
. O
As O
an O
exception O
, O
trigonocephaly O
in O
Bohring O
- O
Opitz O
syndrome O
reflects O
specific O
molecular O
properties O
of O
the O
chromatin O
modifier O
ASXL1 O
gene O
. O
Surveillance O
for O
craniosynostosis O
in O
syndromic O
forms O
of O
intellectual O
disability O
, O
as O
well O
as O
ascertainment O
of O
genomic O
CNVs O
by O
array O
- O
CGH O
in O
apparently O
non O
- O
syndromic O
craniosynostosis O
is O
recommended O
, O
to O
allow O
for O
improvement O
of O
both O
the O
clinical O
outcome O
of O
patients O
and O
the O
accurate O
individual O
diagnosis O
. O
Background O
: O
Osteogenesis O
imperfecta O
( O
OI O
) O
is O
a O
rare O
disease O
characterized O
by O
increased O
bone O
fragility O
and O
susceptibility O
for O
fractures O
. O
Only O
few O
studies O
have O
compared O
the O
management O
for O
femoral O
fractures O
in O
children O
with O
OI O
. O
Nevertheless O
, O
no O
cohort O
studies O
have O
described O
the O
treatment O
for O
femoral O
fractures O
in O
adults O
with O
OI O
in O
Taiwan B-LOC
. O
This O
study O
aimed O
to O
investigate O
and O
compare O
the O
incidence B-EPI
of O
union O
and O
non O
- O
union O
femoral O
fractures O
and O
the O
best O
treatment O
options O
to O
avoid O
non O
- O
union O
fractures O
. O
Methods O
: O
We O
enrolled O
72 O
patients O
with O
OI O
who O
were O
older O
than O
18 O
years O
at O
MacKay O
Memorial O
Hospital O
between O
January O
2010 O
and O
December O
2018 O
. O
Femoral O
fracture O
incidence B-EPI
, O
non O
- O
union O
rate O
, O
and O
treatment O
modality O
were O
analyzed O
. O
Results O
: O
Of O
72 O
patients O
with O
OI O
, O
11 O
patients O
had O
femoral O
fractures O
and O
4 O
patients O
of O
them O
had O
> O
1 O
femoral O
fracture O
. O
The O
incidence B-EPI
for O
all O
types O
of O
femoral O
fractures O
was O
651 B-STAT
fractures I-STAT
per I-STAT
100,000 I-STAT
person I-STAT
- O
years O
annually O
. O
In O
15 O
total O
fractures O
, O
4 O
fractures O
resulted O
in O
non O
- O
union O
, O
and O
patients O
with O
type O
4 O
OI O
mostly O
had O
shaft O
fractures O
. O
The O
best O
outcomes O
for O
non O
- O
union O
shaft O
fracture O
is O
achieved O
by O
surgical O
treatment O
. O
Conclusion O
: O
Adults O
with O
OI O
tended O
to O
develop O
femoral O
fractures O
and O
non O
- O
unions O
. O
Adults O
with O
type O
4 O
OI O
were O
particularly O
at O
high O
risk O
for O
non O
- O
unions O
in O
shaft O
fractures O
with O
conservative O
treatment O
. O
Background O
A O
systematic O
review O
and O
meta O
- O
analysis O
were O
made O
of O
the O
incidence B-EPI
of O
recurrences O
in O
patients O
with O
proliferative O
verrucous O
leukoplakia O
( O
PVL O
) O
subjected O
to O
different O
types O
of O
treatment O
. O
Methods O
The O
study O
was O
carried O
out O
following O
the O
Preferred O
Reporting O
Items O
for O
Systematic O
Reviews O
and O
Meta O
- O
Analyses O
( O
PRISMA O
) O
statement O
guidelines O
. O
A O
literature O
search O
was O
made O
in O
the O
Medline O
( O
PubMed O
) O
, O
EMBASE O
, O
and O
Web O
of O
Science O
databases O
, O
together O
with O
a O
manual O
search O
, O
covering O
the O
period O
from O
1985 O
to O
January O
2020 O
, O
with O
no O
language O
restrictions O
. O
Studies O
were O
included O
if O
they O
described O
treatments O
applied O
to O
at O
least O
10 O
patients O
with O
the O
corresponding O
outcomes O
. O
Methodological O
quality O
was O
evaluated O
using O
Jadad B-LOC
scale O
and O
Newcastle B-LOC
- O
Ottawa B-LOC
tool O
. O
Global O
incidence B-EPI
was O
calculated O
by O
random O
effects O
meta O
- O
analysis O
using O
the O
Comprehensive O
Meta O
- O
analysis O
version O
3.0 O
software O
. O
Publication O
bias O
was O
assessed O
using O
funnel O
plots O
and O
the O
Duval O
and O
Tweedie O
trim O
and O
fill O
method O
. O
Results O
Of O
the O
922 O
identified O
articles O
, O
12 O
were O
found O
to O
meet O
the O
inclusion O
criteria O
. O
Most O
of O
them O
presented O
moderate O
or O
low O
risk O
of O
bias O
. O
A O
total O
of O
397 O
patients O
were O
analyzed O
. O
The O
mean O
age O
was O
62.34 O
years O
and O
248 O
were O
women O
( O
62.5 O
% O
) O
. O
The O
mean O
follow O
- O
up O
was O
79.3 O
months O
. O
The O
most O
frequent O
treatment O
was O
surgical O
removal O
with O
a O
cold O
scalpel O
or O
laser O
( O
339 O
patients O
) O
. O
A O
total O
of O
232 O
subjects O
presented O
lesion O
recurrence O
. O
The O
combination O
of O
proportions O
global O
effect O
meta O
- O
analysis O
yielded O
a O
recurrence O
rate O
of O
67.2 O
% O
( O
95 O
% O
CI O
: O
48.3 O
- O
81.8 O
) O
, O
with O
the O
absence O
of O
publication O
bias O
. O
Conclusions O
There O
is O
not O
enough O
scientific O
evidence O
to O
conclude O
that O
any O
treatment O
strategy O
is O
able O
to O
reduce O
the O
recurrence O
in O
PVL O
. O
Coronavirus O
2019 O
disease O
( O
COVID-19 O
) O
is O
associated O
with O
coagulation O
dysfunction O
that O
predisposes O
patients O
to O
an O
increased O
risk O
for O
both O
arterial O
( O
ATE O
) O
and O
venous O
thromboembolism O
( O
VTE O
) O
and O
consequent O
poor O
prognosis O
; O
in O
particular O
, O
the O
incidence B-EPI
of O
ATE O
and O
VTE O
in O
critically O
ill O
COVID-19 O
patients O
can O
reach O
5 O
% O
and O
31 O
% O
, O
respectively O
. O
The O
mechanism O
of O
thrombosis O
in O
COVID-19 O
patients O
is O
complex O
and O
still O
not O
completely O
clear O
. O
Recent O
literature O
suggests O
a O
link O
between O
the O
presence O
of O
antiphospholipid O
antibodies O
( O
aPLs O
) O
and O
thromboembolism O
in O
COVID-19 O
patients O
. O
However O
, O
it O
remains O
uncertain O
whether O
aPLs O
are O
an O
epiphenomenon O
or O
are O
involved O
in O
the O
pathogenesis O
of O
the O
disease O
. O
Background O
: O
Twenty O
- O
one O
- O
hydroxylase O
- O
deficient O
non O
- O
classic O
adrenal O
hyperplasia O
( O
NC O
- O
CAH O
) O
is O
a O
very O
common O
autosomal O
recessive O
syndrome O
with O
prevalence B-EPI
between O
1:1,000 B-STAT
and O
1:2,000 B-STAT
individuals I-STAT
and I-STAT
the O
frequency O
varies O
according O
to O
ethnicity O
. O
On O
the O
other O
hand O
, O
polycystic O
ovary O
syndrome O
has O
a O
familial O
basis O
and O
it O
is O
inherited O
under O
a O
complex O
hereditary O
trait O
. O
This O
syndrome O
affects O
6 B-STAT
to O
10 O
% O
of O
women O
in O
reproductive O
age O
and O
it O
is O
the O
most O
common O
endocrine O
disorder O
in O
young O
women O
. O
Our O
aim O
was O
to O
investigate O
, O
through O
a O
systematic O
review O
, O
the O
distinct O
characteristics O
and O
common O
findings O
of O
these O
syndromes O
. O
Methods O
: O
The O
search O
period O
covered O
January O
1970 O
to O
November O
2018 O
, O
using O
the O
scientific O
databases O
PubMed O
. O
Inclusion O
criteria O
were O
adult O
women O
patients O
with O
PCOS O
or O
NC O
- O
CAH O
. O
Search O
terms O
were O
O
polycystic O
ovary O
syndrome O
, O
O
O
PCOS O
, O
O
O
non O
- O
classical O
adrenal O
hyperplasia O
, O
O
O
NC O
- O
CAH O
, O
O
O
21 O
- O
hydroxylase O
deficiency O
. O
O
From O
an O
initial O
16,255 O
titles O
, O
the O
evaluations O
led O
to O
the O
final O
inclusion O
of O
97 O
papers O
. O
Results O
: O
The O
clinical O
features O
of O
NC B-LOC
- O
CAH O
are O
hirsutism O
and O
ovulatory O
and O
menstrual O
dysfunction O
therefore O
; O
differentiation O
between O
these O
two O
syndromes O
is O
difficult O
based O
on O
clinical O
grounds O
only O
. O
Additionally O
, O
NC B-LOC
- O
CAH O
and O
PCOS O
are O
both O
associated O
with O
obesity O
, O
insulin O
resistance O
, O
and O
dyslipidaemia O
. O
Reproductive O
abnormalities O
are O
also O
common O
between O
these O
hyperandrogenemic O
disorders O
since O
in O
patients O
with O
NC B-LOC
- O
CAH O
polycystic O
ovarian O
morphology O
and O
subfertility O
are O
present O
as O
they O
are O
in O
women O
with O
PCOS O
. O
The O
diagnosis O
of O
PCOS O
, O
is O
confirmed O
once O
other O
disorders O
that O
mimic O
PCOS O
have O
been O
excluded O
e.g. O
, O
conditions O
that O
are O
related O
to O
oligoovulation O
or O
anovulation O
and/or O
hyperandrogenism O
, O
such O
as O
hyperprolactinaemia O
, O
thyroid O
disorders O
, O
non O
- O
classic O
congenital O
adrenal O
hyperplasia O
, O
and O
androgen O
- O
producing O
neoplasms O
. O
Conclusions O
: O
The O
screening O
tool O
to O
distinguish O
non O
- O
classic O
adrenal O
hyperplasia O
from O
PCOS O
is O
the O
measurement O
of O
17 O
- O
hydroxyprogesterone O
levels O
. O
The O
basal O
levels O
of O
17 O
- O
hydroxyprogesterone O
may O
overlap O
, O
but O
ACTH O
stimulation O
testing O
can O
distinguish O
the O
two O
entities O
. O
In O
this O
review O
these O
two O
common O
endocrine O
disorders O
are O
discussed O
in O
an O
effort O
to O
unveil O
their O
commonalities O
and O
to O
illuminate O
their O
shadowed O
distinctive O
characteristics O
. O
AIM O
: O
The O
aim O
of O
this O
study O
was O
to O
develop O
an O
algorithm O
to O
prompt O
early O
clinical O
suspicion O
of O
mucopolysaccharidosis O
type O
I O
( O
MPS O
I O
) O
. O
METHODS O
: O
An O
international O
working O
group O
was O
established O
in O
2016 O
that O
comprised O
11 O
experts O
in O
paediatrics O
, O
rare O
diseases O
and O
inherited O
metabolic O
diseases O
. O
They O
reviewed O
real O
- O
world O
clinical O
cases O
, O
selected O
key O
signs O
or O
symptoms O
based O
on O
their O
prevalence B-EPI
and O
specificity O
and O
reached O
consensus O
about O
the O
algorithm O
. O
The O
algorithm O
was O
retrospectively O
tested O
. O
RESULTS O
: O
An O
algorithm O
was O
developed O
. O
In O
patients O
under O
two O
years O
of O
age O
, O
kyphosis O
or O
gibbus O
deformity O
were O
the O
key O
symptoms O
that O
raised O
clinical O
suspicion O
of O
MPS O
I O
and O
in O
those O
over O
two O
years O
they O
were O
kyphosis O
or O
gibbus O
deformity O
, O
or O
joint O
stiffness O
or O
contractures O
without O
inflammation O
. O
The O
algorithm O
was O
tested O
on O
35 O
cases O
, O
comprising O
16 O
Hurler O
, O
10 O
Hurler O
- O
Scheie O
, O
and O
nine O
Scheie O
patients O
. O
Of O
these O
35 O
cases O
, O
32 B-STAT
( O
91 O
% O
) O
- O
16 O
Hurler O
, O
nine O
Hurler O
- O
Scheie O
and O
seven O
Scheie O
patients O
- O
would O
have O
been O
referred O
earlier O
if O
the O
algorithm O
had O
been O
used O
. O
CONCLUSION O
: O
The O
expert O
panel O
developed O
and O
tested O
an O
algorithm O
that O
helps O
raise O
clinical O
suspicion O
of O
MPS O
I O
and O
would O
lead O
to O
a O
more O
prompt O
final O
diagnosis O
and O
allow O
earlier O
treatment O
. O
Urea O
cycle O
disorders O
( O
UCDs O
) O
are O
rare O
inherited O
metabolic O
conditions O
that O
impair O
the O
effectiveness O
of O
the O
urea O
cycle O
responsible O
for O
removing O
excess O
ammonia O
from O
the O
body O
. O
The O
estimated B-EPI
incidence I-EPI
of O
UCDs O
is O
1:35 B-STAT
000 I-STAT
births I-STAT
, I-STAT
or O
approximately O
113 O
new O
patients O
with O
UCD O
per O
year O
. O
This O
review O
summarizes O
neuropsychological O
outcomes O
among O
patients O
with O
the O
eight O
UCDs O
in O
reports O
published O
since O
1980 O
. O
Rates O
of O
intellectual O
disabilities O
published O
before O
( O
and O
including O
) O
2000 O
and O
after O
2000 O
were O
pooled O
and O
compared O
for O
each O
UCD O
. O
Since O
diagnoses O
for O
UCDs O
tended O
to O
occur O
earlier O
and O
better O
treatments O
became O
more O
readily O
available O
after O
the O
turn O
of O
the O
century O
, O
this O
assessment O
will O
characterize O
the O
extent O
that O
current O
management O
strategies O
have O
improved O
neuropsychological O
outcomes O
. O
The O
pooled O
sample O
included O
data O
on O
cognitive O
abilities O
of O
1649 O
individuals O
reported O
in O
58 O
citations O
. O
A O
total O
of O
556 O
patients O
( O
34 O
% O
) O
functioned O
in O
the O
range O
of O
intellectual O
disabilities O
. O
The O
decline O
in O
the O
proportion O
of O
intellectual O
disabilities O
in O
six O
disorders O
, O
ranged O
from O
7 O
% O
to O
41 O
% I-STAT
. O
Results O
from O
various O
studies O
differed O
and O
the O
cohorts O
varied O
with O
respect O
to O
age O
at O
symptom O
onset O
, O
age O
at O
diagnosis O
and O
treatment O
initiation O
, O
current O
age O
, O
severity O
of O
the O
metabolic O
deficiency O
, O
management O
strategies O
, O
and O
ethnic O
origins O
. O
The O
proportion O
of O
cases O
with O
intellectual O
disabilities O
ranged O
from O
9 O
% O
to O
65 O
% O
after O
2000 O
in O
the O
seven O
UCDs O
associated O
with O
cognitive O
deficits O
. O
Positive O
outcomes O
from O
some O
studies O
suggest O
that O
it O
is O
possible O
to O
prevent O
or O
reverse O
the O
adverse O
impact O
of O
UCDs O
on O
neuropsychological O
functioning O
. O
It O
is O
time O
to O
O
raise O
the O
bar O
O
in O
terms O
of O
expectations O
for O
treatment O
effectiveness O
. O
The O
diagnosis O
of O
autoimmune O
polyglandular O
syndrome O
( O
APS O
) O
types O
1/2 B-STAT
is O
difficult O
due O
to O
their O
rarity O
and O
nonspecific O
clinical O
manifestations O
. O
APS-1 O
development O
can O
be O
identified O
with O
assays O
for O
autoantibodies O
against O
cytokines O
, O
and O
APS-2 O
development O
with O
organ O
- O
specific O
antibodies O
. O
In O
this O
study O
, O
a O
microarray O
- O
based O
multiplex O
assay O
was O
proposed O
for O
simultaneous O
detection O
of O
both O
organ O
- O
specific O
( O
anti-21 O
- O
OH O
, O
anti O
- O
GAD-65 O
, O
anti O
- O
IA2 O
, O
anti O
- O
ICA O
, O
anti O
- O
TG O
, O
and O
anti O
- O
TPO O
) O
and O
APS-1 O
- O
specific O
( O
anti O
- O
IFN O
- O
ω O
, O
anti O
- O
IFN O
- O
α-2a O
, O
and O
anti O
- O
IL-22 O
) O
autoantibodies O
. O
Herein O
, O
206 O
serum O
samples O
from O
adult O
patients O
with O
APS-1 O
, O
APS-2 B-LOC
, O
isolated O
autoimmune O
endocrine O
pathologies O
or O
non O
- O
autoimmune O
endocrine O
pathologies O
and O
from O
healthy O
donors O
were O
analyzed O
. O
The O
prevalence B-EPI
of O
autoantibodies O
differed O
among O
the O
groups O
of O
healthy O
donors O
and O
patients O
with O
non- O
, O
mono- O
and O
multi O
- O
endocrine O
diseases O
. O
APS-1 O
patients O
were O
characterized O
by O
the O
presence O
of O
at O
least O
two O
specific O
autoantibodies O
( O
specificity O
99.5 O
% O
, O
sensitivity O
100 O
% O
) O
. O
Furthermore O
, O
in O
16 O
of O
the O
18 O
patients O
, O
the O
APS-1 O
assay O
revealed O
triple O
positivity O
for O
autoantibodies O
against O
IFN O
- O
ω O
, O
IFN O
- O
α-2a O
and O
IL-22 O
( O
specificity O
100 O
% O
, O
sensitivity O
88.9 O
% O
) O
. O
No O
anti O
- O
cytokine O
autoantibodies O
were O
found O
in O
the O
group O
of O
patients O
with O
non O
- O
APS-1 O
polyendocrine O
autoimmunity O
. O
The O
accuracy O
of O
the O
microarray O
- O
based O
assay O
compared O
to O
ELISA O
for O
organ O
- O
specific O
autoantibodies O
was O
88.8 B-STAT
- I-STAT
97.6 I-STAT
% I-STAT
. O
This O
multiplex O
assay O
can O
be O
part O
of O
the O
strategy O
for O
diagnosing O
and O
predicting O
the O
development O
of O
APS O
. O
We O
have O
studied O
36 O
patients O
with O
HPRT O
deficiency O
, O
25 O
with O
Lesch O
- O
Nyhan O
syndrome O
and O
11 O
with O
partial O
HPRT O
deficiency O
( O
grades O
1 B-STAT
to I-STAT
3 I-STAT
) O
. O
Patients O
diagnosed O
with O
HPRT O
deficiency O
have O
increased O
50 O
% O
since O
2000 O
. O
The O
most O
relevant O
recent O
advances O
have O
been O
made O
in O
molecular O
diagnosis O
. O
Nevertheless O
, O
enzyme O
determinations O
are O
still O
essential O
for O
the O
diagnosis O
of O
HPRT O
deficiency O
. O
Therapy O
for O
the O
neurological O
manifestations O
of O
HPRT O
deficiency O
has O
not O
advanced O
. O
Allopurinol O
remains O
the O
drug O
of O
choice O
to O
diminish O
uric O
acid O
overproduction O
, O
but O
the O
optimal O
allopurinol O
dose O
must O
be O
established O
in O
each O
patient O
to O
prevent O
xanthine O
or O
uric O
acid O
urolithiasis O
, O
a O
process O
aided O
by O
sequential O
determination O
of O
urinary O
oxypurines O
and O
uric O
acid O
. O
Introduction O
Obstructive O
sleep O
apnea O
is O
highly O
prevalent B-EPI
in O
non O
- O
syndromic O
Pierre O
Robin O
sequence O
patients O
. O
Studies O
have O
found O
a O
probable O
relationship O
between O
obstructive O
sleep O
apnea O
and O
nasal O
obstruction O
and O
between O
obstructive O
sleep O
apnea O
and O
enuresis O
. O
Assessment O
of O
the O
relationship O
between O
these O
variables O
in O
non O
- O
syndromic O
Pierre O
Robin O
sequence O
patients O
is O
scarce O
. O
Objective O
The O
present O
study O
aims O
to O
evaluate O
the O
relationship O
between O
symptoms O
of O
obstructive O
sleep O
apnea O
, O
nasal O
obstruction O
and O
enuresis O
, O
determining O
the O
prevalence B-EPI
of O
symptoms O
suggestive O
of O
these O
conditions O
, O
in O
schoolchildren O
with O
non O
- O
syndromic O
Pierre O
Robin O
sequence O
, O
and O
describe O
the O
prevalence B-EPI
of O
excessive O
daytime O
sleepiness O
habitual O
snoring O
and O
voiding O
dysfunction O
symptoms O
associated O
with O
enuresis O
. O
Methods O
This O
was O
a O
prospective O
analytical O
cross O
- O
sectional O
study O
developed O
at O
a O
reference O
center O
. O
Anthropometric O
measurements O
and O
a O
structured O
clinical O
interview O
were O
carried O
out O
in O
a O
sample O
of O
48 O
patients O
. O
The O
instruments O
O
sleep O
disorders O
scale O
in O
children O
O
O
nasal O
congestion O
index O
questionnaire O
O
( O
CQ-5 O
) O
, O
and O
the O
O
voiding O
dysfunction O
symptom O
score O
questionnaire O
O
were O
used O
. O
Statistical O
analysis O
was O
performed O
for O
p O
< O
0.05 O
. O
Results O
Positive O
O
sleep O
disorders O
scale O
in O
children O
O
scores O
for O
obstructive O
sleep O
apnea O
and O
CQ-5 O
for O
nasal O
obstruction O
were O
observed O
in O
38.78 O
% O
and O
16.33 O
% O
, O
respectively O
. O
Enuresis O
was O
reported O
in O
16.33 O
% O
of O
children O
, O
being O
characterized O
as O
primary O
in O
71.43 O
% O
and O
polysymptomatic O
in O
55.55 O
% O
; O
according O
to O
the O
O
voiding O
dysfunction O
symptom O
score O
questionnaire O
O
. O
There O
was O
a O
significant O
relationship O
between O
nasal O
obstruction O
and O
obstructive O
sleep O
apnea O
symptoms O
( O
p O
< O
0.05 O
) O
, O
but O
no O
significance O
was O
found O
between O
obstructive O
sleep O
apnea O
symptoms O
and O
enuresis O
, O
and O
between O
nasal O
obstruction O
and O
enuresis O
. O
The O
prevalence B-EPI
of O
excessive O
daytime O
sleepiness O
was O
12.24 O
% O
and O
of O
habitual O
snoring O
, O
48.98 B-STAT
% I-STAT
. O
A O
family O
history O
of O
enuresis O
, O
younger O
age O
in O
years O
and O
a O
positive O
O
voiding O
dysfunction O
symptom O
score O
questionnaire O
O
score O
were O
associated O
with O
a O
higher O
prevalence B-EPI
of O
enuresis O
( O
p O
< O
0.05 O
) O
. O
Conclusion O
Children O
with O
non O
- O
syndromic O
Pierre O
Robin O
sequence O
are O
at O
high O
risk O
for O
obstructive O
sleep O
apnea O
symptoms O
and O
habitual O
snoring O
, O
with O
a O
correlation O
being O
observed O
between O
nasal O
obstruction O
and O
obstructive O
sleep O
apnea O
symptoms O
. O
In O
addition O
, O
the O
study O
showed O
that O
non O
- O
syndromic O
Pierre O
Robin O
sequence O
, O
obstructive O
sleep O
apnea O
and O
nasal O
obstruction O
symptoms O
were O
not O
risk O
factors O
for O
enuresis O
in O
these O
patients O
. O
Hepatocellular O
carcinoma O
( O
HCC O
) O
is O
the O
most O
common O
primary O
cancer O
of O
the O
liver O
with O
high O
morbidity O
and O
mortality O
rates O
worldwide B-LOC
. O
Since O
1963 O
, O
when O
alpha O
- O
fetoprotein O
( O
AFP O
) O
was O
discovered O
as O
a O
first O
HCC O
serum O
biomarker O
, O
several O
other O
protein O
biomarkers O
have O
been O
identified O
and O
introduced O
into O
clinical O
practice O
. O
However O
, O
insufficient O
specificity O
and O
sensitivity O
of O
these O
biomarkers O
dictate O
the O
necessity O
of O
novel O
biomarker O
discovery O
. O
Remarkable O
advancements O
in O
integrated O
multiomics O
technologies O
for O
the O
identification O
of O
gene O
expression O
and O
protein O
or O
metabolite O
distribution O
patterns O
can O
facilitate O
rising O
to O
this O
challenge O
. O
Current O
multiomics O
technologies O
lead O
to O
the O
accumulation O
of O
a O
huge O
amount O
of O
data O
, O
which O
requires O
clustering O
and O
finding O
correlations O
between O
various O
datasets O
and O
developing O
predictive O
models O
for O
data O
filtering O
, O
pre O
- O
processing O
, O
and O
reducing O
dimensionality O
. O
Artificial O
intelligence O
( O
AI O
) O
technologies O
have O
an O
enormous O
potential O
to O
overcome O
accelerated O
data O
growth O
, O
complexity O
, O
and O
heterogeneity O
within O
and O
across O
data O
sources O
. O
Our O
review O
focuses O
on O
the O
recent O
progress O
in O
integrative O
proteomic O
profiling O
strategies O
and O
their O
usage O
in O
combination O
with O
machine O
learning O
and O
deep O
learning O
technologies O
for O
the O
discovery O
of O
novel O
biomarker O
candidates O
for O
HCC O
early O
diagnosis O
and O
prognosis O
. O
We O
discuss O
conventional O
and O
promising O
proteomic O
biomarkers O
of O
HCC O
such O
as O
AFP O
, O
lens O
culinaris O
agglutinin O
( O
LCA)-reactive O
L3 O
glycoform O
of O
AFP O
( O
AFP O
- O
L3 O
) O
, O
des O
- O
gamma O
- O
carboxyprothrombin O
( O
DCP O
) O
, O
osteopontin O
( O
OPN O
) O
, O
glypican-3 O
( O
GPC3 O
) O
, O
dickkopf-1 O
( O
DKK1 O
) O
, O
midkine O
( O
MDK O
) O
, O
and O
squamous O
cell O
carcinoma O
antigen O
( O
SCCA O
) O
and O
highlight O
their O
functional O
significance O
including O
the O
involvement O
in O
cell O
signaling O
such O
as O
Wnt O
/ O
β O
- O
catenin O
, O
PI3K O
/ O
Akt O
, O
integrin O
αvβ3 O
/ O
NF O
- O
κB O
/ O
HIF-1α O
, O
JAK O
/ O
STAT3 O
and O
MAPK O
/ O
ERK O
- O
mediated O
pathways O
dysregulated O
in O
HCC O
. O
We O
show O
that O
currently O
available O
computational O
platforms O
for O
big O
data O
analysis O
and O
AI O
technologies O
can O
both O
enhance O
proteomic O
profiling O
and O
improve O
imaging O
techniques O
to O
enhance O
the O
translational O
application O
of O
proteomics O
data O
into O
precision O
medicine O
. O
Congenital O
hypothyroidism O
( O
CH O
) O
is O
a O
thyroid O
hormone O
deficiency O
syndrome O
in O
newborns O
resulting O
from O
incomplete O
thyroid O
development O
and O
decreased O
thyroid O
hormone O
biosynthesis O
or O
thyroid O
- O
stimulating O
hormone O
secretion O
. O
Without O
early O
treatment O
, O
newborns O
with O
CH O
have O
irreversible O
neurological O
deficits O
and O
long O
- O
term O
metabolic O
complications O
. O
Therefore O
, O
several O
countries O
have O
implemented O
widespread O
newborn O
screening O
to O
identify O
and O
treat O
CH O
in O
newborns O
. O
Although O
newborn O
screening O
has O
improved O
diagnosis O
and O
treatment O
outcomes O
for O
CH O
, O
several O
questions O
remain O
concerning O
the O
etiology O
and O
increased O
incidence B-EPI
of O
CH O
in O
different O
populations O
. O
Moreover O
, O
the O
increase O
in O
the O
number O
of O
preterm O
, O
low O
- O
birth O
- O
weight O
newborns O
and O
of O
newborns O
admitted O
to O
the O
neonatal O
intensive O
care O
unit O
presenting O
with O
CH O
requires O
additional O
research O
to O
detect O
and O
treat O
all O
forms O
of O
CH O
. O
Introduction O
Children O
account O
for O
a O
relatively O
small O
proportion O
of O
laboratory O
- O
confirmed O
SARS O
- O
CoV-2 O
infections O
. O
In O
children O
, O
COVID-19 O
usually O
has O
a O
relatively O
mild O
course O
. O
However O
, O
in O
rare O
cases O
, O
severe O
disorders O
can O
be O
observed O
, O
and O
clinical O
manifestations O
may O
differ O
from O
adults O
. O
Purpose O
The O
aim O
of O
this O
study O
is O
to O
analyse O
the O
frequency O
, O
clinical O
picture O
and O
outcome O
of O
COVID-19 O
in O
children O
based O
on O
the O
experience O
from O
the O
tertiary O
care O
centre O
and O
regional O
sanitary O
- O
epidemiological O
office O
. O
Methods O
We O
report O
a O
study O
regarding O
106 O
cases O
of O
confirmed O
SARS O
- O
CoV-2 O
infection O
cases O
in O
PCR O
from O
a O
nasopharyngeal O
swab O
( O
age O
range O
1 O
- O
month O
- O
17 O
- O
years O
) O
. O
In O
all O
cases O
, O
history O
was O
taken O
. O
In O
children O
who O
required O
hospital O
admission O
, O
physical O
examination O
and O
laboratory O
test O
were O
performed O
according O
to O
clinical O
indications O
. O
Results O
Twelve O
of O
the O
patients O
required O
admission O
to O
the O
hospital O
. O
The O
most O
common O
symptoms O
were O
anosmia O
and O
dysgeusia O
( O
75 O
% O
) O
and O
headaches O
( O
49 O
% O
) O
in O
outpatients O
and O
fever O
in O
hospitalised O
children O
( O
75 O
% O
) O
. O
Three O
children O
from O
the O
hospitalised O
group O
developed O
a O
severe O
course O
with O
increased O
inflammatory O
indexes O
. O
The O
clinical O
picture O
was O
more O
severe O
in O
younger O
children O
from O
the O
hospitalised O
group O
. O
Treatment O
options O
were O
regarded O
individually O
in O
all O
cases O
. O
Conclusion O
Our O
study O
is O
the O
first O
tour O
knowledge O
regarding O
the O
clinical O
course O
of O
COVID-19 O
in O
Polish O
children O
. O
In O
general O
, O
the O
clinical O
course O
of O
COVID-19 O
was O
mild O
with O
anosmia O
and O
dysgeusia O
as O
the O
most O
common O
symptoms O
. O
However O
, O
in O
hospitalised O
children O
, O
a O
severe O
progression O
of O
the O
disease O
and O
less O
typical O
signs O
as O
aplastic O
anaemia O
may O
be O
developed O
. O
MYH9 O
-related O
disease O
( O
MYH9 O
-RD O
) O
is O
an O
autosomal O
- O
dominant O
thrombocytopenia O
caused O
by O
mutations O
in O
the O
gene O
for O
non O
- O
muscle O
myosin O
heavy O
chain O
IIA O
( O
NMMHC O
- O
IIA O
) O
. O
Patients O
present O
congenital O
macrothrombocytopenia O
and O
inclusions O
of O
NMMHC O
- O
IIA O
in O
leukocytes O
, O
and O
have O
a O
variable O
risk O
of O
developing O
kidney O
damage O
, O
sensorineural O
deafness O
, O
presenile O
cataracts O
and/or O
liver O
enzymes O
abnormalities O
. O
The O
spectrum O
of O
mutations O
found O
in O
MYH9 O
-RD O
patients O
is O
limited O
and O
the O
incidence B-EPI
and O
severity O
of O
the O
non O
- O
congenital O
features O
are O
predicted O
by O
the O
causative O
MYH9 O
variant O
. O
In O
particular O
, O
different O
alterations O
of O
the O
C O
- O
terminal O
tail O
domain O
of O
NMMHC O
- O
IIA O
associate O
with O
remarkably O
different O
disease O
evolution O
. O
We O
report O
four O
novel O
MYH9 O
mutations O
affecting O
the O
tail O
domain O
of O
NMMHC O
- O
IIA O
and O
responsible O
for O
MYH9 O
-RD O
in O
four O
families O
. O
Two O
variants O
cause O
amino O
acid O
substitutions O
in O
the O
coiled O
- O
coil O
region O
of O
NMMHC O
- O
IIA O
, O
while O
the O
other O
two O
are O
a O
splicing O
variant O
and O
a O
single O
nucleotide O
deletion O
both O
resulting O
in O
frameshift O
alterations O
of O
the O
short O
non O
- O
helical O
tailpiece O
. O
Characterization O
of O
phenotypes O
of O
affected O
individuals O
shows O
that O
all O
of O
these O
novel O
variants O
are O
associated O
with O
a O
mild O
clinical O
evolution O
of O
the O
disease O
. O
Introduction O
Angelman O
syndrome O
( O
AS O
) O
is O
a O
neurodevelopmental O
disorder O
characterized O
by O
cognitive O
disability O
, O
speech O
impairment O
, O
hyperactivity O
and O
seizures O
. O
Movement O
disorders O
have O
been O
reported O
in O
almost O
all O
AS O
subjects O
and O
they O
are O
described O
as O
O
tremulous O
movements O
of O
limbs O
, O
unsteadiness O
, O
clumsiness O
or O
quick O
, O
jerky O
motions O
O
. O
The O
presence O
of O
dystonia O
has O
barely O
been O
mentioned O
in O
subjects O
with O
AS O
and O
has O
never O
been O
studied O
in O
detail O
. O
The O
purpose O
of O
this O
study O
is O
to O
evaluate O
the O
prevalence B-EPI
, O
clinical O
features O
and O
severity O
of O
dystonia O
in O
a O
series O
of O
adolescents O
and O
adults O
with O
AS O
. O
Methods O
Whole O
body O
video O
recordings O
of O
patients O
with O
genetically O
confirmed O
AS O
were O
evaluated O
. O
Dystonia O
was O
evaluated O
by O
mean O
of O
the O
movement O
subscale O
of O
Burke O
- O
Fahn O
- O
Marsden O
Dystonia O
Rating O
Scale O
( O
BFM O
) O
. O
Results O
Forty O
- O
four O
subjects O
with O
AS O
were O
evaluated O
. O
Fourteen O
recordings O
were O
excluded O
due O
to O
poor O
cooperation O
. O
We O
finally O
analyzed O
data O
of O
30 O
subjects O
( O
15 O
F O
) O
with O
a O
median O
age O
of O
28 O
years O
( O
range O
15 O
- O
51 O
) O
. O
Dystonia O
was O
present O
in O
28/30 B-STAT
( O
93.3 O
% O
) O
subjects O
. O
Among O
these O
, O
dystonia O
involved O
the O
upper O
limbs O
in O
28/28 B-STAT
( O
100 O
% O
) O
, O
lower O
limbs O
in O
8/28 B-STAT
( O
28.5 O
% O
) O
, O
mouth O
in O
7/28 B-STAT
( O
25 O
% O
) O
, O
neck O
in O
3/28 B-STAT
( O
10.7 O
% O
) O
, O
trunk O
in O
1/28 B-STAT
( O
3.6 O
% O
) O
. O
Severity O
of O
dystonia O
ranged O
from O
slight O
to O
moderate O
. O
There O
was O
a O
linear O
correlation O
between O
severity O
of O
dystonia O
and O
increasing O
age O
. O
There O
was O
no O
difference O
in O
terms O
of O
severity O
of O
dystonia O
among O
genetic O
subgroups O
. O
Conclusions O
Dystonia O
is O
a O
common O
and O
previously O
underrecognized O
clinical O
feature O
of O
adults O
and O
adolescents O
with O
AS O
. O
Background O
and O
aims O
Hybanthus O
austrocaledonicus O
( O
Violaceae O
) O
is O
a O
nickel O
( O
Ni O
) O
hyperaccumulator O
endemic O
to O
New B-LOC
Caledonia I-LOC
. O
One O
of O
the O
specimens O
stored O
at O
the O
local O
herbarium O
had O
a O
strip O
of O
bark O
with O
a O
remarkably O
green O
phloem O
tissue O
attached O
to O
the O
sheet O
containing O
over O
4 O
wt% O
Ni O
. O
This O
study O
aimed O
to O
collect O
field O
samples O
from O
the O
original O
H. O
austrocaledonicus O
locality O
to O
confirm O
the O
nature O
of O
the O
green O
' O
nickel O
- O
rich O
phloem O
' O
in O
this O
taxon O
and O
to O
systematically O
assess O
the O
occurrence B-EPI
of O
Ni O
hyperaccumulation O
in O
H. O
austrocaledonicus O
and O
Hybanthus O
caledonicus O
populations O
. O
Methods O
X O
- O
ray O
fluorescence O
spectroscopy O
scanning O
of O
all O
collections O
of O
the O
genus O
Hybanthus O
( O
236 O
specimens O
) O
was O
undertaken O
at O
the O
Herbarium O
of O
New O
Caledonia O
to O
reveal O
incidences B-EPI
of O
Ni O
accumulation O
in O
populations O
of O
H. O
austrocaledonicus O
and O
H. O
caledonicus O
. O
In O
parallel O
, O
micro O
- O
analytical O
investigations O
were O
performed O
via O
synchrotron O
X O
- O
ray O
fluorescence O
microscopy O
( O
XFM O
) O
and O
scanning O
electron O
microscopy O
with O
X O
- O
ray O
microanalysis O
( O
SEM O
- O
EDS O
) O
. O
Key O
results O
The O
extensive O
scanning O
demonstrated O
that O
Ni O
hyperaccumulation O
is O
not O
a O
characteristic O
common O
to O
all O
populations O
in O
the O
endemic O
Hybanthus O
species O
. O
Synchrotron O
XFM O
revealed O
that O
Ni O
was O
exclusively O
concentrated O
in O
the O
epidermal O
cells O
of O
the O
leaf O
blade O
and O
petiole O
, O
conforming O
with O
the O
majority O
of O
( O
tropical O
) O
Ni O
hyperaccumulator O
plants O
studied O
to O
date O
. O
SEM O
- O
EDS O
of O
freeze O
- O
dried O
and O
frozen O
- O
hydrated O
samples O
revealed O
the O
presence O
of O
dense O
solid O
deposits O
in O
the O
phloem O
bundles O
that O
contained O
> O
8 O
wt% O
nickel O
. O
Conclusions O
The O
occurrence B-EPI
of O
extremely O
Ni O
- O
rich O
green O
phloem O
tissues O
appears O
to O
be O
a O
characteristic O
feature O
of O
tropical O
Ni O
hyperaccumulator O
plants O
. O
Acute O
kidney O
injury O
( O
AKI O
) O
is O
a O
fatal O
complication O
of O
the O
new O
severe O
acute O
respiratory O
syndrome O
coronavirus O
( O
SARS O
- O
CoV-2 O
) O
which O
causes O
COVID-19 O
disease O
. O
Here O
, O
we O
performed O
a O
scoping O
review O
and O
meta O
- O
analysis O
including O
clinical O
studies O
on O
patients O
with O
SARS O
- O
CoV-2 O
infection O
with O
data O
on O
AKI O
assessment O
and O
characteristics O
, O
and O
the O
overall B-EPI
prevalence I-EPI
of O
AKI O
was O
estimated O
using O
a O
random O
- O
effects O
model O
. O
We O
identified O
21 O
articles O
which O
passed O
the O
search O
criteria O
. O
All O
were O
quantitative O
observational O
studies O
which O
used O
a O
cross O
- O
sectional O
, O
retrospective O
, O
case O
report O
, O
or O
cohort O
methodology O
. O
This O
showed O
that O
aging O
, O
diabetes O
, O
cardiovascular O
disease O
, O
previous O
chronic O
disease O
, O
and O
other O
comorbidities O
were O
risk O
factors O
of O
AKI O
. O
Although O
the O
prevalence B-EPI
of O
proteinuria O
, O
hematuria O
, O
and O
increased O
serum O
creatinine O
was O
reported O
for O
up O
to O
60 B-STAT
% O
of O
the O
patients O
with O
COVID-19 O
, O
the O
overall B-EPI
prevalence I-EPI
of O
AKI O
was O
estimated O
to O
be O
8 B-STAT
% I-STAT
. O
We O
conclude O
that O
although O
approximately O
two O
- O
thirds O
of O
patients O
with O
COVID-19 O
had O
symptoms O
of O
kidney O
damage O
, O
most O
of O
these O
did O
not O
meet O
the O
diagnostic O
criteria O
for O
AKI O
. O
Further O
studies O
should O
be O
performed O
to O
validate O
biomarkers O
for O
improved O
AKI O
diagnosis O
in O
COVID-19 O
patients O
and O
new O
treatment O
options O
are O
required O
to O
reduce O
the O
rate O
of O
mortality O
. O
In O
this O
paper O
, O
the O
author O
enumerates O
cardiac O
defects O
with O
a O
functionally O
single O
ventricle O
, O
summarizes O
single O
ventricle O
physiology O
, O
presents O
a O
summary O
of O
management O
strategies O
to O
address O
the O
single O
ventricle O
defects O
, O
goes O
over O
the O
steps O
of O
staged O
total O
cavo O
- O
pulmonary O
connection O
, O
cites O
the O
prevalence B-EPI
of O
inter O
- O
stage O
mortality O
, O
names O
the O
causes O
of O
inter O
- O
stage O
mortality O
, O
discusses O
strategies O
to O
address O
the O
inter O
- O
stage O
mortality O
, O
reviews O
post O
- O
Fontan O
issues O
, O
and O
introduces O
alternative O
approaches O
to O
Fontan O
circulation O
. O
Introduction O
21 O
- O
hydroxylase O
deficiency O
( O
21 O
- O
OHD O
) O
is O
the O
most O
common O
form O
of O
congenital O
adrenal O
hyperplasia O
( O
CAH O
) O
. O
In O
adulthood O
, O
most O
studies O
are O
reported O
in O
females O
. O
By O
contrast O
, O
data O
on O
adult O
males O
are O
scarce O
. O
Objective O
To O
describe O
a O
series O
of O
adult O
males O
with O
classic O
21 O
- O
OHD O
and O
to O
assess O
the O
presence O
of O
adrenal O
masses O
and O
testicular O
adrenal O
rest O
tumors O
( O
TARTs O
) O
. O
Material O
and O
methods O
Eight O
males O
( O
21 O
- O
42 O
years O
) O
were O
included O
. O
We O
evaluated O
clinical O
presentation O
, O
17 O
- O
Hydroxyprogesterone O
( O
17 O
- O
OHP O
) O
, O
Testosterone O
( O
T O
) O
, O
Δ4Androstenedione O
( O
Δ4A O
) O
ACTH O
, O
LH O
, O
FSH O
and O
plasma O
renin O
activitiy O
( O
PRA O
) O
levels O
at O
consultation O
. O
Molecular O
studies O
of O
the O
CYP21A2 O
gene O
, O
testicular O
ultrasound O
( O
US B-LOC
) O
, O
semen O
analysis O
and O
adrenal O
computed O
tomography O
( O
CT O
) O
scan O
were O
performed O
. O
Treatment O
and O
compliance O
were O
assessed O
. O
Results O
Basal O
17 O
- O
OHP O
levels O
were O
> O
20ng O
/ O
ml O
in O
all O
patients O
. O
At O
consultation O
, O
median O
17OH O
- O
P O
was O
11.5 O
( O
2.3 O
- O
81 O
) O
ng O
/ O
ml O
, O
FSH O
: O
3 O
( O
0.3 O
- O
4 O
) O
mUI O
/ O
ml O
, O
LH O
: O
1.1 O
( O
0.1 O
- O
6 O
) O
mUI O
/ O
ml O
, O
T O
: O
4.3 O
( O
1.7 O
- O
8) O
ng O
/ O
ml O
, O
Δ4A O
: O
5.7 O
( O
1.4 O
- O
16 O
) O
ng O
/ O
ml O
, O
ACTH O
: O
86.4 O
( O
76 O
- O
334 O
) O
pg O
/ O
ml O
, O
PRA O
: O
9.5 O
( O
1.3 O
- O
23.6 O
) O
ng O
/ O
ml O
/ O
h. O
Semen O
analysis O
was O
performed O
in O
5/8 B-STAT
patients O
, O
showing O
azoospermia O
in O
two O
. O
Molecular O
genetic O
analysis O
was O
performed O
in O
4/8 B-STAT
patients O
. O
TARTs O
were O
found O
in O
5/6 B-STAT
, O
being O
bilateral O
in O
four O
. O
Adrenal O
masses O
were O
found O
in O
4/6 B-STAT
. O
In O
the O
7 O
patients O
diagnosed O
in O
childhood O
, O
their O
follow O
- O
up O
was O
referred O
to O
as O
irregular O
, O
both O
in O
their O
attendance O
at O
consultations O
and O
in O
compliance O
with O
the O
indicated O
treatment O
. O
Conclusions O
To O
our O
knowledge O
, O
this O
is O
the O
first O
series O
on O
adult O
males O
with O
classic O
21 O
- O
OHD O
which O
concomitantly O
assesses O
clinical O
presentation O
, O
molecular O
biology O
, O
adrenal O
and O
testicular O
imaging O
studies O
, O
semen O
analysis O
and O
compliance O
to O
treatment O
. O
A O
high O
prevalence B-EPI
of O
adrenal O
masses O
and O
TARTs O
was O
observed O
, O
possibly O
associated O
with O
poor O
treatment O
compliance O
leading O
to O
elevated O
ACTH O
and O
increased O
proliferation O
. O
Our O
findings O
on O
TARTs O
agree O
with O
reports O
in O
international O
publications O
of O
CAH O
in O
males O
, O
with O
adrenal O
imaging O
being O
added O
in O
our O
group O
. O
Although O
we O
are O
aware O
that O
further O
studies O
with O
a O
larger O
sample O
size O
and O
more O
data O
are O
needed O
, O
we O
consider O
that O
our O
findings O
contribute O
to O
the O
clinical O
management O
of O
classical O
21 O
- O
OHD O
in O
the O
male O
population O
. O
Background O
Q O
fever O
osteoarticular O
infections O
are O
a O
rare O
complication O
of O
the O
chronic O
form O
of O
Q O
fever O
. O
We O
aimed O
to O
characterize O
chronic O
Q O
fever O
vertebral O
osteomyelitis O
through O
our O
experience O
and O
a O
review O
of O
the O
literature O
. O
Methods O
Four O
adult O
patients O
with O
Q O
fever O
vertebral O
osteomyelitis O
diagnosed O
in O
a O
tertiary O
hospital O
in O
northern O
Israel B-LOC
between O
2016 O
to O
2020 O
are O
described O
. O
In O
addition O
, O
a O
30 O
years O
' O
literature O
review O
of O
Q O
fever O
vertebral O
osteomyelitis O
, O
characterizing O
predisposing O
factors O
, O
clinical O
presentation O
, O
course O
of O
disease O
, O
treatment O
and O
outcomes O
, O
was O
performed O
. O
Results O
Thirty O
- O
four O
adult O
patients O
with O
Q O
fever O
vertebral O
osteomyelitis O
were O
identified O
. O
The O
vast O
majority O
were O
male O
( O
30/34 B-STAT
, O
88 O
% O
) O
with O
a O
mean O
age O
of O
67.2 O
± O
10 O
years O
. O
Involvement O
of O
the O
adjacent O
aorta O
, O
likely O
the O
origin O
of O
the O
infection O
, O
was O
observed O
in O
23/34 B-STAT
( O
68 O
% O
) O
of O
the O
patients O
, O
usually O
among O
patients O
with O
aortic O
graft O
or O
aneurysm O
. O
Clinical O
presentation O
was O
insidious O
and O
fever O
was O
frequently O
absent O
. O
Delayed O
diagnosis O
for O
months O
to O
years O
after O
symptoms O
onset O
was O
frequently O
reported O
. O
Vascular O
infections O
were O
managed O
with O
or O
without O
extraction O
of O
the O
infected O
aneurysm O
/ O
aorta O
and O
graft O
placement O
. O
The O
outcome O
was O
variable O
with O
limited O
follow O
- O
up O
data O
in O
most O
cases O
. O
Patients O
were O
usually O
treated O
with O
prolonged O
antimicrobial O
therapy O
, O
most O
commonly O
doxycycline O
and O
hydroxychloroquine O
combination O
therapy O
. O
Conclusion O
Q O
fever O
should O
be O
included O
in O
the O
differential O
diagnosis O
of O
vertebral O
osteomyelitis O
in O
endemic O
settings O
, O
in O
particular O
when O
concomitant O
adjacent O
vascular O
infection O
exists O
. O
Since O
the O
discovery O
of O
the O
FMR1 O
gene O
and O
the O
clinical O
and O
molecular O
characterization O
of O
Fragile O
X O
Syndrome O
in O
1991 O
, O
more O
than O
141 O
genes O
have O
been O
identified O
in O
the O
X O
- O
chromosome O
in O
these O
28 O
years O
thanks O
to O
applying O
continuously O
evolving O
molecular O
techniques O
to O
X O
- O
linked O
intellectual O
disability O
( O
XLID O
) O
families O
. O
In O
the O
past O
decade O
, O
array O
comparative O
genomic O
hybridization O
and O
next O
generation O
sequencing O
technologies O
have O
accelerated O
gene O
discovery O
exponentially O
. O
Classically O
, O
XLID O
has O
been O
subdivided O
in O
syndromic O
intellectual O
disability O
( O
S O
- O
XLID)-where O
intellectual O
disability O
( O
ID O
) O
is O
always O
associated O
with O
other O
recognizable O
physical O
and/or O
neurological O
features O
- O
and O
non O
- O
specific O
or O
non O
- O
syndromic O
intellectual O
disability O
( O
NS O
- O
XLID O
) O
where O
the O
only O
common O
feature O
is O
ID O
. O
Nevertheless O
, O
new O
advances O
on O
the O
study O
of O
these O
entities O
have O
showed O
that O
this O
classification O
is O
not O
always O
clear O
- O
cut O
because O
distinct O
variants O
in O
several O
of O
these O
XLID O
genes O
can O
result O
in O
S O
- O
XLID O
as O
well O
as O
in O
NS O
- O
XLID O
. O
This O
review O
focuses O
on O
the O
current O
knowledge O
on O
the O
XLID O
genes O
involved O
in O
non O
- O
syndromic O
forms O
, O
with O
the O
emphasis O
on O
their O
pathogenic O
mechanism O
, O
thus O
allowing O
the O
possibility O
to O
elucidate O
why O
some O
of O
them O
can O
give O
both O
syndromic O
and O
non O
- O
syndromic O
phenotypes O
. O
Background O
: O
Endolymphatic O
hydrops O
( O
EH O
) O
is O
the O
histopathological O
hallmark O
of O
Ménière O
's O
disease O
( O
MD O
) O
and O
has O
been O
found O
by O
in O
vivo O
magnetic O
resonance O
imaging O
( O
MRI O
) O
in O
patients O
with O
several O
inner O
ear O
syndromes O
without O
definite O
MD B-LOC
criteria O
. O
The O
incidence B-EPI
and O
relevance O
of O
this O
finding O
is O
under O
debate O
. O
Purpose O
: O
The O
purpose O
of O
the O
study O
is O
to O
evaluate O
the O
prevalence B-EPI
and O
characteristics O
of O
EH O
and O
audiovestibular O
test O
results O
in O
groups O
of O
patients O
with O
fluctuating O
audiovestibular O
symptoms O
not O
fulfilling O
the O
actual O
criteria O
for O
definite O
MD B-LOC
and O
compare O
them O
with O
a O
similar O
group O
of O
patients O
with O
definite O
MD B-LOC
and O
a O
group O
of O
patients O
with O
recent O
idiopathic O
sudden O
neurosensory O
hearing O
loss O
( O
ISSNHL O
) O
. O
Material O
and O
Methods O
: O
170 O
patients O
were O
included O
, O
83 O
with O
definite O
MD B-LOC
, O
38 O
with O
fluctuating O
sensorineural O
hearing O
loss O
, O
34 O
with O
recurrent O
vertigo O
, O
and O
15 O
with O
ISSNHL O
. O
The O
clinical O
variables O
, O
audiovestibular O
tests O
, O
and O
EH O
were O
evaluated O
and O
compared O
. O
Logistic O
proportional O
hazard O
models O
were O
used O
to O
obtain O
the O
odds O
ratio O
for O
hydrops O
development O
, O
including O
a O
multivariable O
adjusted O
model O
for O
potential O
confounders O
. O
Results O
: O
No O
statistical O
differences O
between O
groups O
were O
found O
regarding O
disease O
duration O
, O
episodes O
, O
Tumarkin O
spells O
, O
migraine O
, O
vascular O
risk O
factors O
, O
or O
vestibular O
tests O
; O
only O
hearing O
loss O
showed O
differences O
. O
Regarding O
EH O
, O
we O
found O
significant O
differences O
between O
groups O
, O
with O
odds O
ratio O
( O
OR O
) O
for O
EH O
presence O
in O
definite O
MD B-LOC
group O
vs. O
all O
other O
patients O
of O
11.43 O
( O
4.5 O
- O
29.02 O
; O
p O
< O
0.001 O
) O
. O
If O
the O
ISSNHL O
group O
was O
used O
as O
reference O
, O
OR O
was O
55.2 O
( O
11.9 O
- O
253.9 O
; O
p O
< O
0.001 O
) O
for O
the O
definite O
MD B-LOC
group O
, O
9.9 O
( O
2.1 O
- O
38.9 O
; O
p O
= O
0.003 O
) O
for O
the O
recurrent O
vertigo O
group O
, O
and O
5.1 O
( O
1.2 O
- O
21.7 O
; O
p O
= O
0.03 O
) O
for O
the O
group O
with O
fluctuating O
sensorineural O
hearing O
loss O
. O
Conclusion O
: O
The O
percentage O
of O
patients O
with O
EH O
varies O
between O
groups O
. O
It O
is O
minimal O
in O
the O
ISSNHL O
group O
and O
increases O
in O
groups O
with O
increasing O
fluctuating O
audiovestibular O
symptoms O
, O
with O
a O
rate O
of O
severe O
EH O
similar O
to O
the O
known O
rate O
of O
progression O
to O
definite O
MD B-LOC
in O
those O
groups O
, O
suggesting O
that O
presence O
of O
EH O
by O
MRI O
could O
be O
related O
to O
the O
risk O
of O
progression O
to O
definite O
MD B-LOC
. O
Thus O
, O
EH O
imaging O
in O
these O
patients O
is O
recommended O
. O
Congenital O
factor O
X O
( O
FX O
) O
deficiency O
is O
a O
rare O
bleeding O
disorder O
with O
an O
incidence B-EPI
of O
one O
in O
one O
million O
. O
The O
proband O
, O
a O
2 O
- O
year O
- O
old O
girl O
, O
exhibited O
easy O
bruising O
and O
a O
history O
of O
umbilical O
cord O
bleeding O
at O
birth O
. O
Prothrombin O
time O
( O
> O
40 O
s O
) O
and O
activated O
partial O
thromboplastin O
time O
( O
65.0 O
s O
) O
were O
prolonged O
. O
Marked O
declines O
in O
FX O
activity O
( O
< O
1 O
% O
) O
and O
FX O
antigen O
levels O
( O
5 O
% O
) O
were O
also O
observed O
. O
Genetic O
analysis O
of O
the O
proband O
identified O
two O
types O
of O
single O
- O
base O
substitutions O
, O
c.353G O
> O
A O
( O
p. O
Gly118Asp O
) O
and O
c.1303G O
> O
A O
( O
p. O
Gly435Ser O
) O
, O
indicating O
compound O
heterozygous O
congenital O
FX O
deficiency O
. O
Genetic O
analysis O
of O
family O
members O
revealed O
that O
her O
father O
and O
older O
sister O
( O
5 O
- O
year O
- O
old O
) O
were O
also O
heterozygous O
for O
p. O
Gly118Asp O
, O
and O
that O
her O
mother O
was O
heterozygous O
for O
p. O
Gly435Ser O
. O
To O
improve O
the O
bleeding O
tendency O
, O
the O
proband O
received O
regular O
replacement O
of O
500 O
units O
of O
PPSB O
- O
HT O
, O
a O
prothrombin O
complex O
concentrate O
( O
PCC O
) O
. O
Following O
continued O
regular O
replacement O
of O
500 O
units O
of O
PPSB O
- O
HT O
once O
per O
week O
, O
the O
proband O
has O
exhibited O
no O
bleeding O
tendencies O
and O
no O
new O
bruises O
have O
been O
observed O
. O
There O
are O
no O
previous O
report O
of O
the O
use O
of O
PPSB O
- O
HT O
for O
regular O
FX O
replacement O
. O
Regular O
replacement O
therapy O
with O
PPSB O
- O
HT O
may O
be O
an O
effective O
method O
for O
preventative O
control O
of O
bleeding O
tendencies O
in O
FX O
deficiency O
. O
Coronavirus O
disease O
2019 O
( O
COVID-19 O
) O
is O
emerging O
as O
the O
greatest O
public O
health O
crisis O
in O
the O
early O
21 O
st O
century O
. O
Its O
causative O
agent O
, O
Severe O
Acute O
Respiratory O
Syndrome O
coronavirus O
2 O
( O
SARS O
- O
CoV-2 O
) O
, O
is O
an O
enveloped O
single O
stranded O
positive O
- O
sense O
ribonucleic O
acid O
virus O
that O
enters O
cells O
via O
the O
angiotensin O
converting O
enzyme O
2 O
receptor O
or O
several O
other O
receptors O
. O
While O
COVID-19 O
primarily O
affects O
the O
respiratory O
system O
, O
other O
organs O
including O
the O
brain O
can O
be O
involved O
. O
In O
Western O
clinical O
studies O
, O
relatively O
mild O
neurological O
dysfunction O
such O
as O
anosmia O
and O
dysgeusia O
is O
frequent O
( O
~70 B-STAT
- O
84 O
% O
) O
while O
severe O
neurologic O
disorders O
such O
as O
stroke O
( O
~1 O
- O
6 O
% O
) O
and O
meningoencephalitis O
are O
less O
common O
. O
It O
is O
unclear O
how O
much O
SARS O
- O
CoV-2 O
infection O
contributes O
to O
the O
incidence B-EPI
of O
stroke O
given O
co O
- O
morbidities O
in O
the O
affected O
patient O
population O
. O
Rarely O
, O
clinically O
- O
defined O
cases O
of O
acute O
disseminated O
encephalomyelitis O
, O
Guillain O
- O
Barré O
syndrome O
and O
acute O
necrotizing O
encephalopathy O
have O
been O
reported O
in O
COVID-19 O
patients O
. O
Common O
neuropathological O
findings O
in O
the O
184 O
patients O
reviewed O
include O
microglial O
activation O
( O
42.9 O
% O
) O
with O
microglial O
nodules O
in O
a O
subset O
( O
33.3 O
% O
) O
, O
lymphoid O
inflammation O
( O
37.5 O
% O
) O
, O
acute O
hypoxic O
- O
ischemic O
changes O
( O
29.9 O
% O
) O
, O
astrogliosis O
( O
27.7 O
% O
) O
, O
acute O
/ O
subacute O
brain O
infarcts O
( O
21.2 O
% O
) O
, O
spontaneous O
hemorrhage O
( O
15.8 O
% O
) O
, O
and O
microthrombi O
( O
15.2 O
% O
) O
. O
In O
our O
institutional O
cases O
, O
we O
also O
note O
occasional O
anterior O
pituitary O
infarcts O
. O
COVID-19 O
coagulopathy O
, O
sepsis O
, O
and O
acute O
respiratory O
distress O
likely O
contribute O
to O
a O
number O
of O
these O
findings O
. O
When O
present O
, O
central O
nervous O
system O
lymphoid O
inflammation O
is O
often O
minimal O
to O
mild O
, O
is O
detected O
best O
by O
immunohistochemistry O
and O
, O
in O
one O
study O
, O
indistinguishable O
from O
control O
sepsis O
cases O
. O
Some O
cases O
evince O
microglial O
nodules O
or O
neuronophagy O
, O
strongly O
supporting O
viral O
meningoencephalitis O
, O
with O
a O
proclivity O
for O
involvement O
of O
the O
medulla O
oblongata O
. O
The O
virus O
is O
detectable O
by O
reverse O
transcriptase O
polymerase O
chain O
reaction O
, O
immunohistochemistry O
, O
or O
electron O
microscopy O
in O
human O
cerebrum O
, O
cerebellum O
, O
cranial O
nerves O
, O
olfactory O
bulb O
, O
as O
well O
as O
in O
the O
olfactory O
epithelium O
; O
neurons O
and O
endothelium O
can O
also O
be O
infected O
. O
Review O
of O
the O
extant O
cases O
has O
limitations O
including O
selection O
bias O
and O
limited O
clinical O
information O
in O
some O
cases O
. O
Much O
remains O
to O
be O
learned O
about O
the O
effects O
of O
direct O
viral O
infection O
of O
brain O
cells O
and O
whether O
SARS O
- O
CoV-2 O
persists O
long O
- O
term O
contributing O
to O
chronic O
symptomatology O
. O
Few O
studies O
have O
investigated O
transient O
global O
amnesia O
( O
TGA O
) O
in O
the O
context O
of O
a O
concussion O
and O
the O
concussion O
sequelae O
following O
TGA O
. O
Here O
we O
review O
the O
case O
of O
a O
43 O
- O
year O
- O
old O
male O
with O
onset O
of O
transient O
global O
anterograde O
and O
retrograde O
amnesia O
22 O
days O
after O
a O
sustained O
concussion O
. O
The O
patient O
's O
head O
CT O
, O
MRI O
of O
brain O
, O
and O
EEG O
were O
reported O
normal O
, O
and O
the O
patient O
regained O
full O
cognitive O
function O
8 O
h O
after O
the O
TGA O
episode O
, O
with O
no O
recollection O
of O
the O
conspiring O
events O
. O
Following O
the O
TGA O
episode O
, O
the O
patient O
experienced O
notable O
worsening O
of O
concussive O
symptoms O
, O
including O
headache O
, O
head O
pressure O
, O
anxiety O
, O
neck O
pain O
, O
feeling O
slowed O
down O
, O
fogginess O
, O
not O
feeling O
right O
, O
difficulty O
remembering O
, O
and O
fatigue O
. O
The O
patient O
remained O
symptomatic O
for O
32 O
days O
after O
the O
TGA O
episode O
. O
We O
suggest O
that O
a O
lingering O
window O
of O
post O
- O
concussion O
cerebral O
vulnerability O
, O
which O
may O
extend O
beyond O
clinical O
recovery O
, O
could O
lead O
to O
increased O
susceptibility O
to O
acute O
cognitive O
deficits O
, O
such O
as O
TGA O
. O
Background O
and O
purpose O
Vascular O
Ehlers O
- O
Danlos O
syndrome O
is O
a O
rare O
inherited O
connective O
tissue O
disorder O
because O
of O
pathogenic O
variants O
in O
the O
COL3A1 O
gene O
. O
Arterial O
complications O
can O
affect O
all O
anatomic O
areas O
and O
about O
25 O
% O
involve O
supra O
- O
aortic O
trunks O
( O
SATs O
) O
but O
no O
systematic O
assessment O
of O
cervical O
artery O
lesions O
has O
been O
made O
. O
The O
primary O
objective O
was O
to O
determine O
an O
accurate O
prevalence B-EPI
of O
spontaneous O
SAT O
lesions O
in O
a O
large O
series O
of O
patients O
with O
vascular O
Ehlers O
- O
Danlos O
syndrome O
at O
diagnosis O
and O
during O
follow O
- O
up O
. O
Secondary O
objectives O
were O
to O
study O
their O
neurological O
consequences O
( O
transient O
ischemic O
attack O
or O
stroke O
) O
and O
the O
possible O
relationships O
with O
sex O
, O
genotype O
, O
ascertainment O
status O
. O
Methods O
A O
retrospective O
review O
of O
a O
monocentric O
cohort O
of O
patients O
with O
molecularly O
proven O
vascular O
Ehlers O
- O
Danlos O
syndrome O
followed O
in O
a O
tertiary O
referral O
center O
from O
2000 O
to O
2017 O
. O
Results O
One O
hundred O
forty O
- O
four O
patients O
were O
analyzed O
, O
56.9 O
% O
( O
n=82 O
) O
had O
SAT O
lesions O
: O
64.6 O
% O
females O
, O
74.4 O
% O
index O
- O
case O
patients O
. O
Most O
lesions O
were O
identified O
in O
early O
arterial O
assessment O
( O
48 O
% O
at O
first O
work O
- O
up O
, O
mean O
age O
of O
35.7±13.0 O
years O
) O
. O
Cumulative B-EPI
incidence I-EPI
of O
a O
first O
identification O
of O
a O
SAT O
lesion O
was O
41.7 O
% O
at O
40 O
years O
old O
. O
On O
the O
complete O
period O
of O
survey O
, O
183 O
SAT O
lesions O
( O
with O
132 O
dissections O
and O
33 O
aneurysms O
) O
were O
identified O
, O
mainly O
in O
internal O
carotid O
arteries O
( O
56.3 O
% O
) O
and O
vertebral O
arteries O
( O
28.9 O
% O
) O
, O
more O
rarely O
in O
patients O
with O
COL3A1 O
null O
mutations O
( O
P O
= O
0.008 O
) O
. O
Transient O
ischemic O
attack O
or O
stroke O
were O
reported O
in O
n=16 O
( O
19.5 O
% O
) O
of O
the O
82 O
patients O
with O
SAT O
lesions O
without O
relation O
with O
age O
, O
sex O
, O
treatment O
, O
or O
hypertension O
. O
Conclusions O
Cervical O
artery O
lesions O
are O
frequent O
and O
mostly O
asymptomatic O
in O
patients O
with O
vascular O
Ehlers O
- O
Danlos O
syndrome O
. O
Local O
dissections O
and O
aneurysms O
are O
the O
most O
frequent O
type O
of O
lesions O
, O
but O
transient O
ischemic O
attack O
or O
stroke O
seem O
rare O
. O
Background O
Birth O
defect O
is O
widely O
used O
as O
a O
term O
for O
congenital O
anomalies O
. O
Children O
with O
cleft O
lip O
and O
palate O
may O
have O
serious O
speech O
, O
hearing O
, O
nutrition O
, O
and O
mental O
and O
social O
development O
disorders O
; O
therefore O
, O
this O
study O
was O
designed O
to O
determine O
the O
overall B-EPI
prevalence I-EPI
of O
cleft O
palate O
, O
lip O
, O
and O
cleft O
palate O
through O
systematic O
review O
and O
meta O
- O
analysis O
. O
Methods O
In O
this O
study O
, O
systematic O
review O
and O
meta O
- O
analysis O
of O
data O
from O
studies O
on O
the O
prevalence B-EPI
of O
cleft O
lip O
and O
palate O
in O
Scopus O
, O
Embase O
, O
Magiran B-LOC
, O
Web O
of O
Science O
( O
WoS O
) O
, O
PubMed O
and O
Science O
Direct O
databases O
were O
extracted O
between O
January O
2000 O
and O
June O
2020 O
. O
In O
order O
to O
perform O
the O
analysis O
of O
qualified O
studies O
, O
the O
model O
of O
random O
effects O
was O
used O
and O
the O
inconsistency O
of O
studies O
with O
I O
2 O
index O
was O
investigated O
. O
Data O
analysis O
was O
performed O
with O
Comprehensive O
Meta O
- O
Analysis O
software O
( O
Version O
2 O
) O
. O
Results O
According O
to O
the O
results O
of O
the O
present O
study O
on O
cleft O
palate O
, O
the O
total O
number O
of O
samples O
entered O
in O
the O
study O
in O
59 O
studies O
were O
21,088,517 O
individuals O
, O
the O
prevalence B-EPI
of O
cleft O
palate O
based O
on O
the O
meta O
- O
analysis O
of O
the O
reviewed O
studies O
in O
every O
1000 O
live O
births O
was O
obtained O
0.33 O
( O
95 O
% O
CI O
: O
0.28 O
- O
0.38 O
) O
. O
In O
the O
case O
of O
cleft O
lip O
, O
the O
total O
number O
of O
samples O
entered O
in O
the O
57 O
reviewed O
studies O
were O
17,907,569 O
individuals O
. O
The O
prevalence B-EPI
of O
cleft O
lip O
obtained O
based O
on O
the O
meta O
- O
analysis O
of O
the O
reviewed O
studies O
was O
0.3 O
in O
every O
1000 O
live O
births O
( O
95 O
% O
CI O
: O
0.26 O
- O
0.34 O
) O
, O
and O
in O
the O
case O
of O
cleft O
lip O
and O
palate O
, O
the O
total O
number O
of O
samples O
entered O
in O
the O
55 O
reviewed O
studies O
was O
17,894,673 O
. O
The O
prevalence B-EPI
of O
cleft O
lip O
and O
palate O
based O
on O
the O
meta O
- O
analysis O
of O
the O
studies O
reviewed O
in O
each O
1000 O
live O
births O
was O
0.45 O
( O
95 O
% O
CI O
: O
0.38 O
- O
0.52 O
) O
. O
Conclusion O
Due O
to O
the O
high O
prevalence B-EPI
of O
oral O
clefts O
such O
as O
cleft O
palate O
, O
cleft O
lip O
, O
and O
cleft O
lip O
and O
palate O
; O
health O
system O
policymakers O
need O
to O
take O
precautionary O
measures O
to O
reduce O
the O
number O
of O
patients O
, O
as O
well O
as O
diagnostic O
and O
therapeutic O
measures O
to O
reduce O
the O
effects O
of O
this O
disorder O
in O
children O
. O
To O
evaluate O
the O
incidence B-EPI
and O
predictive O
risk O
factors O
of O
complications O
in O
patients O
who O
underwent O
thyroid O
surgery O
at O
our O
hospital O
with O
a O
residency O
training O
program O
. O
This O
retrospective O
cohort O
study O
analyzed O
the O
complications O
in O
all O
patients O
who O
underwent O
thyroid O
surgery O
between O
January O
2008 O
and O
December O
2017 O
. O
Demographic O
data O
, O
preoperative O
diagnosis O
based O
on O
fine O
needle O
aspiration O
cytology O
, O
surgical O
approach O
, O
permanent O
pathology O
, O
postoperative O
complications O
, O
and O
factors O
associated O
with O
complications O
were O
recorded O
. O
At O
our O
hospital O
, O
456 O
patients O
underwent O
thyroidectomy O
. O
The O
most O
common O
surgical O
complications O
were O
asymptomatic O
biochemical O
hypocalcemia O
and O
symptomatic O
hypocalcemia O
in O
109 B-STAT
( O
23.9 O
% O
) O
and O
50 B-STAT
( O
11 O
% O
) O
patients O
, O
respectively O
. O
Other O
surgical O
complications O
included O
permanent O
hypocalcemia O
, O
transient O
vocal O
cord O
palsy O
, O
permanent O
vocal O
cord O
palsy O
, O
hematoma O
, O
seroma O
, O
chyle O
fistula O
, O
and O
Horner O
's O
syndrome O
. O
Mean O
age O
> O
45 O
years O
and O
more O
extensive O
surgery O
were O
significantly O
associated O
with O
overall O
complications O
( O
P O
= O
0.003 O
; O
< O
0.001 O
) O
. O
Mean O
age O
> O
50 O
years O
and O
vitamin O
D O
level O
< O
25 O
nmol O
/ O
L O
( O
< O
10 O
ng O
/ O
mL O
) O
were O
significantly O
associated O
with O
hypocalcemia O
( O
P O
= O
0.008 O
; O
< O
0.001 O
) O
. O
Moreover O
, O
the O
extent O
of O
surgery O
and O
advanced O
thyroid O
carcinoma O
were O
significantly O
associated O
with O
vocal O
cord O
palsy O
( O
P O
< O
0.001 O
; O
0.05 O
) O
. O
Hypocalcemia O
and O
vocal O
cord O
palsy O
are O
the O
most O
significant O
complications O
. O
Thyroid O
surgery O
can O
be O
performed O
safely O
by O
senior O
residents O
in O
the O
residency O
training O
program O
under O
the O
direct O
supervision O
of O
an O
experienced O
surgeon O
. O
In O
contrast O
to O
acute O
peripheral O
nerve O
injury O
, O
the O
molecular O
response O
of O
Schwann O
cells O
in O
chronic O
neuropathies O
remains O
poorly O
understood O
. O
Onion O
bulb O
structures O
are O
a O
pathological O
hallmark O
of O
demyelinating O
neuropathies O
, O
but O
the O
nature O
of O
these O
formations O
is O
unknown O
. O
Here O
, O
we O
show O
that O
Schwann O
cells O
induce O
the O
expression O
of O
Neuregulin-1 O
type O
I O
( O
NRG1 O
- O
I O
) O
, O
a O
paracrine O
growth O
factor O
, O
in O
various O
chronic O
demyelinating O
diseases O
. O
Genetic O
disruption O
of O
Schwann O
cell O
- O
derived O
NRG1 O
signalling O
in O
a O
mouse O
model O
of O
Charcot O
- O
Marie O
- O
Tooth O
Disease O
1A O
( O
CMT1A O
) O
, O
suppresses O
hypermyelination O
and O
the O
formation O
of O
onion O
bulbs O
. O
Transgenic O
overexpression O
of O
NRG1 O
- O
I O
in O
Schwann O
cells O
on O
a O
wildtype O
background O
is O
sufficient O
to O
mediate O
an O
interaction O
between O
Schwann O
cells O
via O
an O
ErbB2 O
receptor O
- O
MEK O
/ O
ERK O
signaling O
axis O
, O
which O
causes O
onion O
bulb O
formations O
and O
results O
in O
a O
peripheral O
neuropathy O
reminiscent O
of O
CMT1A. O
We O
suggest O
that O
diseased O
Schwann O
cells O
mount O
a O
regeneration O
program O
that O
is O
beneficial O
in O
acute O
nerve O
injury O
, O
but O
that O
overstimulation O
of O
Schwann O
cells O
in O
chronic O
neuropathies O
is O
detrimental O
. O
Background O
/ O
objectives O
This O
retrospective O
study O
evaluated O
the O
prevalence B-EPI
of O
dental O
anomalies O
of O
number O
in O
different O
subphenotypes O
of O
isolated O
cleft O
palate O
. O
Materials O
/ O
methods O
The O
sample O
comprised O
26 O
individuals O
with O
submucous O
cleft O
palate O
( O
group O
S O
) O
and O
68 O
individuals O
with O
complete O
cleft O
palate O
( O
group O
C O
) O
aged O
between O
9 O
and O
12 O
years O
from O
a O
single O
centre O
. O
Panoramic O
radiographs O
were O
evaluated O
regarding O
the O
presence O
of O
dental O
anomalies O
of O
number O
in O
permanent O
teeth O
. O
Intergroup O
comparison O
was O
performed O
using O
chi O
- O
square O
tests O
( O
P O
< O
0.05 O
) O
. O
Results O
Tooth O
agenesis O
was O
found O
in O
34.61 O
and O
36.76 O
per O
cent O
of O
group O
S O
and O
group O
C O
, O
respectively O
. O
The O
most O
commonly O
missing O
teeth O
were O
the O
maxillary O
second O
premolar O
, O
maxillary O
lateral O
incisor O
, O
and O
mandibular O
second O
premolar O
. O
Supernumerary O
teeth O
were O
found O
in O
none O
and O
1.47 O
per O
cent O
of O
the O
individuals O
with O
submucous O
and O
complete O
cleft O
palate O
, O
respectively O
. O
No O
statistically O
significant O
difference O
was O
found O
between O
groups O
for O
the O
frequency O
of O
tooth O
agenesis O
and O
supernumerary O
teeth O
. O
Limitations O
Only O
dental O
anomalies O
of O
number O
were O
evaluated O
. O
Conclusions O
/ O
implications O
Individuals O
with O
submucous O
and O
complete O
cleft O
palate O
showed O
similar O
prevalence B-EPI
for O
tooth O
agenesis O
and O
supernumerary O
teeth O
. O
Dental O
anomalies O
frequency O
seems O
not O
to O
be O
a O
discriminator O
for O
subphenotypes O
of O
cleft O
palate O
. O
Objective O
This O
study O
aimed O
to O
evaluate O
the O
epidemiological O
and O
clinicopathological O
spectrum O
of O
ocular O
malignancies O
among O
patients O
presenting O
to O
a O
teaching O
hospital O
in O
Northern B-LOC
India I-LOC
. O
Methods O
A O
total O
of O
246 O
histopathologically O
diagnosed O
patients O
with O
ocular O
malignancies O
were O
included O
in O
the O
study O
. O
Tumor O
type O
and O
size O
, O
primary O
origin O
and O
location O
of O
tumor O
, O
clinical O
staging O
, O
radiological O
findings O
, O
histopathological O
type O
, O
and O
treatment O
outcomes O
were O
assessed O
. O
Results O
Overall O
, O
males O
over O
55 O
years O
of O
age O
were O
most O
commonly O
affected O
and O
the O
majority O
of O
cases O
were O
primary O
ocular O
or O
adnexal O
malignancies O
( O
n O
= O
226 B-STAT
; O
91.87 O
% O
) O
. O
The O
eyelids O
and O
periocular O
structures O
( O
n O
= O
92 B-STAT
; O
37.40 O
% O
) O
were O
the O
most O
commonly O
involved O
site O
, O
followed O
by O
the O
orbit O
( O
n O
= O
72 B-STAT
; O
29.27 O
% O
) O
, O
ocular O
surface O
( O
n O
= O
46 B-STAT
; O
18.70 O
% O
) O
and O
intraocular O
region O
( O
n O
= O
36 B-STAT
; O
14.63 O
% O
) O
. O
The O
majority O
of O
the O
patients O
( O
n O
= O
68 B-STAT
; O
27.64 O
% O
) O
were O
managed O
by O
primary O
surgical O
excision O
and O
reconstruction O
. O
However O
, O
46 O
patients O
( O
18.70 O
% O
) O
with O
advanced O
lesions O
underwent O
neoadjuvant O
chemotherapy O
followed O
by O
surgical O
excision O
and O
more O
extensive O
orbital O
lesions O
were O
treated O
by O
exenteration O
followed O
by O
adjuvant O
chemotherapy O
( O
n=48 O
; O
19.51 O
% O
) O
, O
while O
patients O
with O
metastatic O
tumor O
were O
given O
palliative O
chemotherapy O
/ O
external O
beam O
radiation O
therapy O
( O
n= O
46 B-STAT
; O
18.70 O
% O
) O
. O
Overall O
, O
45.12 O
% O
of O
patients O
were O
cured O
completely O
, O
15.45 O
% O
showed O
a O
partial O
response O
to O
the O
treatment O
, O
13.04 O
% O
had O
progressive O
disease O
and O
16.67 O
% O
demonstrated O
disease O
recurrence O
. O
Conclusion O
A O
clinicopathological O
analysis O
of O
ocular O
malignancies O
at O
a O
teaching O
hospital O
in O
Northern B-LOC
India I-LOC
indicated O
the O
preponderance O
of O
primary O
ocular O
malignancies O
, O
with O
eyelid O
sebaceous O
gland O
carcinomas O
being O
the O
most O
common O
pathological O
diagnosis O
. O
Most O
of O
our O
patients O
had O
advanced O
and O
extensive O
disease O
among O
them O
majority O
belonged O
to O
the O
rural O
background O
and O
poor O
socio O
- O
economic O
status O
. O
Varicella O
is O
a O
highly O
contagious O
, O
infectious O
disease O
caused O
by O
the O
varicella O
- O
zoster O
virus O
. O
Those O
at O
higher O
risk O
of O
severe O
complications O
are O
immunocompromised O
individuals O
, O
adults O
, O
non O
- O
immune O
pregnant O
women O
, O
and O
newborns O
. O
According O
to O
the O
gestational O
time O
, O
when O
varicella O
- O
zoster O
virus O
infection O
is O
acquired O
during O
pregnancy O
, O
serious O
complications O
can O
potentially O
occur O
for O
both O
the O
woman O
and O
the O
fetus O
. O
The O
present O
study O
was O
conducted O
to O
assess O
the O
profile O
of O
varicella O
susceptibility O
in O
pregnant O
women O
in O
Apulia B-LOC
, O
a O
large O
region O
in O
Southern B-LOC
Italy I-LOC
, O
from O
2016 O
to O
2019 O
. O
The O
data O
showed O
that O
pregnant O
women O
between O
the O
age O
of O
15 O
- O
24 O
and O
40 O
- O
49 O
years O
, O
the O
youngest O
and O
the O
oldest O
, O
respectively O
, O
are O
the O
most O
protected O
against O
varicella O
- O
zoster O
virus O
infection O
, O
exceeding O
the O
prevalence B-EPI
rate O
of O
90 B-STAT
% I-STAT
. O
Conversely O
, O
pregnant O
women O
between O
the O
age O
of O
25 O
and O
34 O
years O
seem O
to O
be O
the O
most O
vulnerable O
and O
the O
most O
at O
risk O
for O
acquiring O
varicella O
- O
zoster O
virus O
infection O
during O
pregnancy O
. O
Analysis O
of O
the O
immunity O
status O
against O
varicella O
should O
be O
introduced O
as O
a O
screening O
test O
before O
pregnancy O
, O
together O
with O
a O
strategic O
vaccination O
campaign O
targeting O
non O
- O
immune O
women O
of O
childbearing O
age O
, O
in O
order O
to O
reduce O
the O
risk O
of O
congenital O
and O
perinatal O
varicella O
. O
Objectives O
Determine O
the O
types O
, O
incidence B-EPI
, O
mortality O
rate O
, O
and O
clinical O
status O
of O
youth O
diabetes O
at O
Bach O
Christian O
Hospital O
( O
BCH B-LOC
) O
, O
Qalandarabad B-LOC
, O
Pakistan B-LOC
. O
Methods O
Analysis O
of O
incidence B-EPI
and O
mortality O
data O
of O
all O
patients O
( O
< O
25 O
year O
( O
y O
) O
) O
diagnosed O
from O
January O
2014 O
- O
June O
2019 O
, O
and O
also O
analysis O
of O
clinical O
status O
of O
patients O
< O
25y O
seen O
in O
2018/2019 O
. O
Results O
Ninety O
- O
three O
patients O
were O
seen O
over O
the O
study O
period O
. O
Eighty O
- O
eight O
were O
type O
1 O
diabetes O
( O
T1D O
) O
, O
51.1 O
% O
female O
. O
Age O
of O
diagnosis O
was O
0.8 O
- O
24.5 O
years O
( O
y O
) O
( O
mean O
= O
11.4 O
y O
, O
SD O
= O
6.2y O
) O
. O
15.1 B-STAT
% I-STAT
were O
0 O
- O
4y O
, O
31.4 O
% O
5 O
- O
9 O
y O
, O
24.4 O
% O
10 O
- O
14y O
, O
19.8 O
% O
15 O
- O
19y O
, O
and O
9.3 O
% O
20 O
- O
24y O
. O
Minimum O
incidence B-EPI
for O
the O
Mansehra O
tehsil O
administrative O
district O
was O
calculated O
as O
1.0 B-STAT
per I-STAT
100,000 I-STAT
population I-STAT
< O
15y O
/ O
y O
, O
1.2 B-STAT
per I-STAT
100,000 I-STAT
< O
20y O
/ O
y O
and O
1.1 B-STAT
per I-STAT
100,000 I-STAT
< O
25y O
/ O
y O
; O
the O
degree O
of O
ascertainment O
could O
not O
be O
assessed O
. O
A O
further O
four O
patients O
were O
diagnosed O
with O
thiamine O
- O
responsive O
megaloblastic O
anaemia O
( O
TRMA O
) O
, O
all O
male O
, O
three O
from O
the O
same O
consanguineous O
family O
, O
and O
were O
treated O
with O
high O
- O
dose O
thiamine O
. O
One O
other O
patient O
was O
diagnosed O
with O
type O
2 O
diabetes O
. O
Three O
T1D O
and O
one O
TRMA O
patient O
died O
during O
the O
study O
period O
. O
The O
standardised O
mortality O
rate O
for O
T1D O
was O
9.4 O
, O
but O
vital O
status O
was O
unknown O
for O
13 O
patients O
. O
The O
mean O
/ O
median O
HbA1c O
of O
T1D O
patients O
seen O
in O
2018/2019 O
was O
9.1%/9.2 O
% O
( O
76/77 O
mmol O
/ O
mol O
) O
. O
Conclusions O
Minimum O
T1D O
incidence B-EPI
in O
Mansehra O
tehsil O
is O
double O
the O
previously O
reported O
value O
for O
Pakistan B-LOC
( O
from O
1990 O
to O
1999 O
) O
, O
although O
is O
still O
low O
compared O
to O
most O
other O
countries O
. O
Considering O
the O
limited O
resources O
available O
, O
patients O
attending O
BCH B-LOC
are O
achieving O
fair O
glycemic O
control O
. O
The O
TRMA O
cases O
show O
the O
importance O
of O
genetic O
testing O
in O
atypical O
cases O
. O
COVID-19 O
( O
coronavirus O
disease O
2019 O
) O
represents O
a O
prothrombotic O
disorder O
, O
and O
there O
have O
been O
several O
reports O
of O
platelet O
factor O
4 O
/ O
heparin O
antibodies O
being O
present O
in O
COVID-19 O
- O
infected O
patients O
. O
This O
has O
thus O
been O
identified O
in O
some O
publications O
as O
representing O
a O
high O
incidence B-EPI
of O
heparin O
- O
induced O
thrombocytopenia O
( O
HIT O
) O
, O
whereas O
in O
others O
, O
findings O
have O
been O
tempered O
by O
general O
lack O
of O
functional O
reactivity O
using O
confirmation O
assays O
of O
serotonin O
release O
assay O
( O
SRA O
) O
or O
heparin O
- O
induced O
platelet O
aggregation O
( O
HIPA O
) O
. O
Moreover O
, O
in O
at O
least O
two O
publications O
, O
data O
are O
provided O
suggesting O
that O
antibodies O
can O
arise O
in O
heparin O
naïve O
patients O
or O
that O
platelet O
activation O
may O
not O
be O
heparin O
- O
dependent O
. O
From O
this O
literature O
, O
we O
would O
conclude O
that O
platelet O
factor O
4 O
/ O
heparin O
antibodies O
can O
be O
observed O
in O
COVID-19 O
- O
infected O
patients O
, O
and O
they O
may O
occur O
at O
higher O
incidence B-EPI
than O
in O
historical O
non O
- O
COVID-19 O
- O
infected O
cohorts O
. O
However O
, O
the O
situation O
is O
complex O
, O
since O
not O
all O
platelet O
factor O
4 O
/ O
heparin O
antibodies O
may O
lead O
to O
platelet O
activation O
, O
and O
not O
all O
identified O
antibodies O
are O
heparin O
- O
dependent O
, O
such O
that O
they O
do O
not O
necessarily O
reflect O
O
true O
O
HIT O
. O
Most O
recently O
, O
a O
O
HIT O
- O
like O
O
syndrome O
has O
reported O
in O
patients O
who O
have O
been O
vaccinated O
against O
COVID-19 O
. O
Accordingly O
, O
much O
more O
is O
yet O
to O
be O
learnt O
about O
the O
insidious O
disease O
that O
COVID-19 O
represents O
, O
including O
autoimmune O
outcomes O
in O
affected O
patients O
. O
After O
a O
female O
patient O
had O
presented O
with O
advanced O
renal O
failure O
, O
bilateral O
enormous O
increase O
in O
kidney O
size O
radiologically O
, O
urinary O
tract O
infection O
( O
E. O
coli O
) O
and O
septicemia O
, O
autopsy O
disclosed O
megalocytic O
interstitial O
nephritis O
( O
MIN O
) O
. O
Clinical O
and O
pathological O
differentiation O
from O
renal O
parenchymal O
malakoplakia O
( O
RPM O
) O
is O
discussed O
. O
A O
literature O
survey O
of O
15 O
cases O
of O
MIN O
and O
35 O
observations O
of O
RPM O
points O
to O
certain O
differences O
between O
the O
two O
entities O
, O
i.e. O
an O
increased O
incidence B-EPI
of O
bilateral O
pathology O
in O
MIN O
, O
mor O
frequent O
extrarenal O
localizations O
in O
RPM O
, O
absent O
Michaelis O
- O
Gutmann O
bodies O
and O
a O
predominantly O
cortical O
distribution O
in O
MIN O
. O
The O
similarities O
, O
however O
, O
suggest O
that O
the O
two O
conditions O
might O
represent O
different O
stages O
of O
one O
and O
the O
same O
disease O
process O
. O
OBJECTIVE O
: O
Intracranial O
aneurysms O
are O
not O
common O
in O
young O
age O
patients O
. O
We O
sought O
to O
find O
the O
characteristics O
of O
the O
intracranial O
aneurysms O
in O
patients O
under O
20 O
years O
of O
age O
. O
METHODS O
: O
We O
reviewed O
23 O
consecutive O
patients O
≤20 O
years O
of O
age O
treated O
for O
their O
intracranial O
aneurysms O
during O
the O
period O
from O
1995 O
to O
2017 O
. O
From O
medical O
records O
and O
imaging O
studies O
, O
we O
gathered O
data O
on O
age O
, O
sex O
, O
presentation O
, O
associated O
medical O
condition O
, O
location O
and O
characteristics O
of O
aneurysms O
, O
treatment O
and O
clinical O
outcomes O
. O
RESULTS O
: O
The O
patients O
' O
ages O
ranged O
from O
13 O
months O
to O
20 O
years O
( O
median O
, O
14 O
years O
) O
. O
There O
were O
16 O
males O
and O
seven O
females O
( O
male O
to O
female O
ratio O
, O
2.3 O
: O
1 B-STAT
) I-STAT
with I-STAT
31 I-STAT
aneurysms O
. O
Clinical O
presentations O
included O
sudden O
severe O
headache O
in O
61 O
% O
, O
followed O
by O
altered O
mentality O
in O
17 O
% O
and O
seizure O
in O
17 B-STAT
% I-STAT
. O
More O
than O
one O
- O
fourth O
patients O
had O
specific O
medical O
conditions O
related O
to O
the O
development O
of O
the O
cerebral O
aneurysms O
. O
The O
majority O
of O
aneurysms O
occurred O
in O
the O
anterior O
circulation O
( O
71 O
% O
) O
, O
and O
were O
saccular O
( O
71 O
% O
) O
. O
There O
were O
each O
three O
patients O
with O
false O
aneurysms O
( O
13 O
% O
) O
and O
giant O
aneurysms O
( O
13 O
% O
) O
, O
and O
only O
one O
patient O
with O
multiple O
aneurysms O
( O
4 O
% O
) O
. O
We O
treated O
22 O
patients O
: O
21 O
aneurysms O
with O
the O
endovascular O
methods O
, O
three O
with O
open O
surgery O
, O
and O
one O
with O
combined O
treatment O
. O
Good O
functional O
outcome O
could O
be O
achieved O
in O
86 O
% O
during O
the O
follow O
- O
up O
period O
. O
CONCLUSION O
: O
In O
this O
series O
, O
the O
young O
- O
age O
patients O
with O
intracranial O
aneurysms O
were O
characterized O
by O
male O
predominance O
, O
related O
specific O
medical O
conditions O
, O
low O
incidence B-EPI
of O
multiple O
aneurysms O
, O
high O
incidence B-EPI
of O
giant O
aneurysms O
and O
good O
functional O
outcome O
after O
treatment O
. O
The O
inherited O
platelet O
glycoprotein O
deficiencies O
, O
Glanzmann O
thrombasthenia O
( O
GT O
) O
and O
Bernard O
Soulier O
syndrome O
( O
BSS O
) O
are O
rare O
but O
important O
long O
- O
term O
bleeding O
disorders O
. O
Once O
diagnosed O
, O
affected O
patients O
should O
be O
referred O
to O
a O
specialist O
centre O
for O
bleeding O
disorders O
for O
general O
advice O
and O
ongoing O
management O
. O
Patients O
do O
not O
require O
prophylactic O
treatment O
and O
so O
the O
management O
of O
GT O
and O
BSS O
focuses O
around O
prophylactic O
treatment O
prior O
to O
high O
risk O
procedures O
and O
treatment O
in O
response O
to O
non O
- O
surgical O
bleeding O
events O
and O
, O
in O
women O
, O
the O
management O
of O
menorrhagia O
and O
pregnancy O
. O
There O
is O
no O
consistent O
approach O
to O
the O
treatment O
or O
prevention O
of O
bleeding O
complications O
. O
Management O
must O
be O
tailored O
for O
each O
individual O
and O
the O
approach O
may O
not O
be O
the O
same O
for O
different O
events O
, O
even O
for O
the O
same O
patient O
, O
depending O
on O
the O
type O
of O
accident O
or O
invasive O
procedure O
, O
the O
extent O
of O
bleeding O
and O
the O
presence O
or O
not O
of O
platelet O
refractoriness O
. O
Herpes O
simplex O
virus O
types O
1 O
( O
HSV-1 O
) O
and O
2 O
( O
HSV-2 O
) O
are O
highly O
prevalent B-EPI
viruses O
capable O
of O
establishing O
lifelong O
infection O
. O
Genital O
herpes O
in O
women O
of O
childbearing O
age O
represents O
a O
major O
risk O
for O
mother O
- O
to O
- O
child O
transmission O
( O
MTCT O
) O
of O
HSV O
infection O
, O
with O
primary O
and O
first O
- O
episode O
genital O
HSV O
infections O
posing O
the O
highest O
risk O
. O
The O
advent O
of O
antiviral O
therapy O
with O
parenteral O
acyclovir O
has O
led O
to O
significant O
improvement O
in O
neonatal O
HSV O
disease O
mortality O
. O
Further O
studies O
are O
needed O
to O
improve O
the O
clinician O
's O
ability O
to O
identify O
infants O
at O
increased O
risk O
for O
HSV O
infection O
and O
prevent O
MTCT O
, O
and O
to O
develop O
novel O
antiviral O
agents O
with O
increased O
efficacy O
in O
infants O
with O
HSV O
infection O
. O
Background O
The O
data O
in O
the O
literature O
suggests O
that O
Methimazole O
( O
MMI)/Carbimazole O
( O
CMZ O
) O
embryopathy O
is O
rare O
. O
This O
study O
examined O
the O
incidence B-EPI
of O
CMZ O
embryopathy O
in O
the B-LOC
Hong I-LOC
Kong I-LOC
Chinese O
population O
and O
the O
factors O
associated O
with O
its O
development O
. O
Methods O
Of O
the O
145 O
pregnant O
women O
with O
hyperthyroidism O
managed O
from O
2008 O
to O
2010 O
, O
29 B-STAT
( O
20 O
% O
) O
had O
taken O
CMZ O
during O
pregnancy O
. O
The O
presence O
and O
details O
of O
birth O
defects O
, O
the O
dosage O
of O
CMZ O
, O
and O
the O
period O
of O
exposure O
during O
pregnancy O
were O
examined O
in O
these O
29 O
pregnancies O
. O
All O
cases O
of O
CMZ O
embryopathy O
in O
the O
English O
literature O
were O
reviewed O
in O
the O
same O
way O
. O
Results O
Of O
the O
27 O
babies O
( O
93.1 O
% O
) O
with O
known O
outcome O
, O
3 O
had O
aplasia O
cutis O
and O
1 O
had O
an O
omphalocele O
in O
addition O
, O
and O
1 O
affected O
baby O
had O
a O
sibling O
with O
aplasia O
cutis O
and O
patent O
vitellointestinal O
duct O
. O
The O
incidence B-EPI
of O
CMZ O
embryopathy O
in O
our O
study O
group O
is O
11.1 B-STAT
% I-STAT
. O
Amongst O
the O
21 O
cases O
of O
CMZ O
embryopathy O
in O
the O
literature O
, O
85 O
% O
were O
exposed O
to O
a O
CMZ O
dosage O
of O
≥20 O
mg O
/ O
day O
, O
and O
the O
minimum O
duration O
of O
exposure O
being O
7 O
weeks O
from O
last O
menstrual O
period O
. O
The O
most O
common O
abnormality O
is O
ectodermal O
anomaly O
( O
62 O
% O
) O
, O
followed O
by O
oro O
- O
nasal O
anomaly O
( O
48 O
% O
) O
, O
facial O
dysmorphism O
( O
38 O
% O
) O
, O
gastrointestinal O
anomaly O
( O
33 O
% O
) O
and O
abdominal O
wall O
defect O
( O
19 O
% O
) O
. O
There O
was O
no O
relationship O
between O
the O
type O
of O
abnormality O
and O
the O
dosage O
or O
duration O
of O
exposure O
to O
CMZ O
. O
Conclusions O
The O
incidence B-EPI
of O
CMZ O
embryopathy O
in O
our O
study O
group O
is O
11.1 B-STAT
% I-STAT
. O
Critical O
factors O
for O
its O
development O
are O
exposure O
to O
a O
CMZ O
dosage O
of O
≥20 O
mg O
/ O
day O
before O
7 O
weeks O
of O
gestation O
. O
Genetic O
susceptibility O
may O
also O
play O
a O
role O
. O
Background O
Orbital O
hypertelorism O
( O
OHT O
) O
represents O
a O
congenital O
condition O
defined O
by O
lateralization O
of O
the O
bony O
orbit O
, O
unlike O
soft O
tissue O
telecanthus O
in O
which O
there O
is O
an O
increase O
in O
intercanthal O
distance O
without O
true O
bony O
lateralization O
. O
Existing O
literature O
remains O
very O
limited O
in O
its O
postoperative O
assessment O
of O
bony O
versus O
soft O
tissue O
relapse O
, O
which O
may O
both O
clinically O
present O
as O
telecanthus O
. O
We O
performed O
a O
critical O
appraisal O
of O
the O
literature O
to O
determine O
the O
postoperative O
incidence B-EPI
of O
bony O
versus O
soft O
tissue O
relapse O
following O
OHT O
repair O
. O
Methods O
The O
PubMed O
, O
MEDLINE O
, O
EMBASE O
, O
Scopus O
, O
Cochrane O
Central O
Register O
of O
Controlled O
Trials O
, O
and O
clinicaltrials.org O
were O
searched O
systematically O
for O
all O
English O
studies O
published O
in O
any O
time O
frame O
reporting O
relapse O
rates O
following O
primary O
OHT O
repair O
. O
The O
primary O
outcome O
was O
incidence B-EPI
of O
bony O
and O
soft O
tissue O
relapse O
defined O
as O
orbital O
lateralization O
and O
medial O
canthal O
drift O
, O
respectively O
. O
The O
secondary O
outcome O
measures O
include O
postoperative O
complications O
, O
predictors O
of O
postoperative O
complications O
, O
timing O
and O
type O
of O
surgery O
, O
and O
revision O
rates O
. O
Results O
Eleven O
articles O
were O
included O
. O
A O
total O
of O
84 B-STAT
( O
35.3 O
% O
) O
patients O
experienced O
bony O
relapse O
while O
43 B-STAT
( O
27.2 O
% O
) O
patients O
experienced O
soft O
tissue O
relapse O
. O
Age O
at O
time O
of O
intervention O
( O
p O
< O
0.92 O
) O
, O
severity O
at O
presentation O
( O
p O
< O
0.90 O
) O
, O
and O
surgical O
technique O
( O
p O
< O
0.09 O
) O
were O
not O
found O
be O
significantly O
associated O
with O
relapse O
rate O
. O
Methods O
for O
long O
- O
term O
follow O
- O
up O
were O
not O
standardized O
, O
and O
there O
was O
no O
consistent O
measure O
to O
objectively O
assess O
telecanthus O
. O
Conclusions O
There O
is O
no O
general O
consensus O
on O
predictive O
factors O
of O
long O
- O
term O
relapse O
following O
OHT O
repair O
in O
the O
form O
of O
box O
osteotomy O
or O
facial O
bipartition O
. O
These O
findings O
call O
for O
cross O
- O
sectional O
outcome O
standardization O
to O
better O
understand O
long O
- O
term O
outcomes O
across O
institutional O
, O
provider O
, O
and O
patient O
differences O
. O
Background O
Human O
lipodystrophies O
are O
uncommon O
disorders O
, O
with O
important O
clinical O
consequences O
, O
which O
are O
often O
undiagnosed O
. O
The O
Barraquer O
- O
Simons O
syndrome O
is O
a O
form O
of O
partial O
symmetric O
lipodystrophy O
of O
unknown O
etiology O
, O
characterized O
by O
the O
loss O
of O
subcutaneous O
adipose O
tissue O
, O
limited O
to O
upper O
part O
of O
the O
body O
. O
Insulin O
resistance O
and O
metabolic O
complications O
are O
less O
common O
than O
with O
other O
lipodystrophy O
subtypes O
. O
Patients O
usually O
have O
decreased O
serum O
complement O
- O
component O
3 O
levels O
, O
associated O
with O
complement O
activation O
by O
the O
alternative O
pathway O
, O
which O
may O
indicate O
the O
presence O
of O
renal O
involvement O
. O
Case O
presentation O
The O
authors O
report O
a O
case O
of O
a O
31 O
- O
year O
- O
old O
woman O
with O
progressive O
loss O
of O
subcutaneous O
fat O
, O
limited O
to O
the O
face O
, O
neck O
and O
thorax O
. O
She O
presented O
no O
severe O
metabolic O
complications O
, O
neither O
signs O
of O
insulin O
resistance O
. O
Laboratory O
tests O
revealed O
mild O
dyslipidemia O
, O
and O
low O
serum O
levels O
of O
complement O
- O
component O
3 O
. O
Clinical O
and O
biochemical O
characteristics O
were O
consistent O
with O
the O
diagnosis O
of O
Barraquer O
- O
Simons O
syndrome O
. O
Conclusion O
The O
present O
case O
illustrates O
the O
importance O
of O
recognizing O
the O
clinical O
features O
of O
this O
lipodystrophic O
syndrome O
, O
which O
may O
present O
potentially O
severe O
consequences O
and O
psychological O
distress O
. O
A O
brief O
overview O
is O
made O
, O
addressing O
the O
clinical O
signs O
of O
the O
disease O
, O
its O
course O
, O
and O
how O
to O
manage O
it O
. O
Significant O
part O
of O
Southeastern B-LOC
Europe I-LOC
( O
with O
a O
population O
of O
76 O
million O
) O
has O
newborn O
screening O
( O
NBS O
) O
programs O
non O
- O
harmonized O
with O
developed O
European O
countries O
. O
Initial O
survey O
was O
conducted O
in O
2013/2014 O
among O
11 O
countries O
from O
the O
region O
( O
Albania B-LOC
, O
Bulgaria B-LOC
, O
Bosnia B-LOC
and I-LOC
Herzegovina I-LOC
( O
BIH O
) O
, O
Croatia B-LOC
, O
Kosovo B-LOC
, O
Macedonia B-LOC
, O
Moldova B-LOC
, O
Montenegro B-LOC
, O
Romania B-LOC
, O
Serbia B-LOC
, O
and O
Slovenia B-LOC
) O
to O
assess O
the O
main O
characteristics O
of O
their O
NBS O
programs O
and O
their O
future O
plans O
. O
Their O
cumulative O
population O
at O
that O
time O
was O
~52,5 O
million O
. O
At O
that O
time O
, O
none O
of O
the O
countries O
had O
an O
expanded O
NBS O
program O
, O
while O
phenylketonuria O
screening O
was O
not O
introduced O
in O
four O
and O
congenital O
hypothyroidism O
in O
three O
of O
11 O
countries O
. O
We O
repeated O
the O
survey O
in O
2020 O
inviting O
the O
same O
11 O
countries O
, O
adding O
Cyprus O
, O
Greece B-LOC
, O
Hungary B-LOC
, O
and O
Malta B-LOC
( O
due O
to O
their O
geographical O
position O
in O
the O
wider O
region O
) O
. O
The O
aims O
were O
to O
assess O
the O
current O
state O
, O
to O
evaluate O
the O
change O
in O
the O
period O
, O
and O
to O
identify O
the O
main O
obstacles O
impacting O
the O
implementation O
of O
expanded O
NBS O
and/or O
reaching O
a O
wider O
population O
. O
Responses O
were O
collected O
from O
12 O
countries O
( O
BIH O
- O
Federation O
of O
BIH O
, O
BIH O
- O
Republic O
of O
Srpska B-LOC
, O
Bulgaria B-LOC
, O
Croatia B-LOC
, O
Greece B-LOC
, O
Hungary B-LOC
, O
Kosovo B-LOC
, O
North B-LOC
Macedonia I-LOC
, O
Malta B-LOC
, O
Montenegro B-LOC
, O
Romania B-LOC
, O
Serbia B-LOC
, O
Slovenia B-LOC
) O
with O
a O
population O
of O
68.5 O
million O
. O
The O
results O
of O
the O
survey O
showed O
that O
the O
regional O
situation O
regarding O
NBS O
only O
modestly O
improved O
in O
this O
period O
. O
All O
of O
the O
surveyed O
countries O
except O
Kosovo B-LOC
screened O
for O
at O
least O
congenital O
hypothyroidism O
, O
while O
phenylketonuria O
was O
not O
screened O
in O
four O
of O
12 O
countries O
. O
Croatia B-LOC
and O
Slovenia B-LOC
implemented O
an O
expanded O
NBS O
program O
using O
tandem O
mass O
spectrometry O
from O
the O
time O
of O
last O
survey O
. O
In O
conclusion O
, O
the O
current O
status O
of O
NBS O
programs O
in O
Southeastern B-LOC
Europe I-LOC
is O
very O
variable O
and O
is O
still O
underdeveloped O
( O
or O
even O
non O
- O
existent O
) O
in O
some O
of O
the O
countries O
. O
We O
suggest O
establishing O
an O
international O
task O
- O
force O
to O
assist O
with O
implementation O
and O
harmonization O
of O
basic O
NBS O
services O
where O
needed O
. O
Background O
: O
Chronic O
kidney O
disease O
( O
CKD O
) O
in O
childhood O
and O
adolescence O
occurs B-EPI
with O
a O
median O
incidence B-EPI
of O
9 B-STAT
per I-STAT
million I-STAT
of I-STAT
the O
age O
- O
related O
population O
. O
Over O
70 O
% O
of O
CKD O
cases O
under O
the O
age O
of O
25 O
years O
can O
be O
attributed O
to O
a O
hereditary O
kidney O
disease O
. O
Among O
these O
are O
hereditary O
podocytopathies O
, O
ciliopathies O
and O
( O
monogenic O
) O
congenital O
anomalies O
of O
the O
kidney O
and O
urinary O
tract O
( O
CAKUT O
) O
. O
These O
disease O
entities O
can O
present O
with O
a O
vast O
variety O
of O
extrarenal O
manifestations O
. O
So O
far O
, O
skeletal O
anomalies O
( O
SA O
) O
have O
been O
infrequently O
described O
as O
extrarenal O
manifestation O
in O
these O
entities O
. O
The O
aim O
of O
this O
study O
was O
to O
retrospectively O
investigate O
a O
cohort O
of O
individuals O
with O
hereditary O
podocytopathies O
, O
ciliopathies O
or O
CAKUT O
, O
in O
which O
molecular O
genetic O
testing O
had O
been O
performed O
, O
for O
the O
extrarenal O
manifestation O
of O
SA O
. O
Material O
and O
Methods O
: O
A O
cohort O
of O
65 O
unrelated O
individuals O
with O
a O
clinically O
presumed O
hereditary O
podocytopathy O
( O
focal O
segmental O
glomerulosclerosis O
, O
steroid O
resistant O
nephrotic O
syndrome O
) O
, O
ciliopathy O
( O
nephronophthisis O
, O
Bardet O
- O
Biedl O
syndrome O
, O
autosomal O
recessive O
/ O
dominant O
polycystic O
kidney O
disease O
) O
, O
or O
CAKUT O
was O
screened O
for O
SA O
. O
Data O
was O
acquired O
using O
a O
standardized O
questionnaire O
and O
medical O
reports O
. O
57/65 B-STAT
( O
88 O
% O
) O
of O
the O
index O
cases O
were O
analyzed O
using O
exome O
sequencing O
( O
ES O
) O
. O
Results O
: O
8/65 B-STAT
( O
12 O
% O
) O
index O
individuals O
presented O
with O
a O
hereditary O
podocytopathy O
, O
ciliopathy O
, O
or O
CAKUT O
and O
an O
additional O
skeletal O
phenotype O
. O
In O
5/8 B-STAT
families O
( O
63 O
% O
) O
, O
pathogenic O
variants O
in O
known O
disease O
- O
associated O
genes O
( O
1x O
BBS1 O
, O
1x O
MAFB O
, O
2x O
PBX1 O
, O
1x O
SIX2 O
) O
could O
be O
identified O
. O
Conclusions O
: O
This O
study O
highlights O
the O
genetic O
heterogeneity O
and O
clinical O
variability O
of O
hereditary O
nephropathies O
in O
respect O
of O
skeletal O
anomalies O
as O
extrarenal O
manifestation O
. O
Barth O
syndrome O
is O
a O
rare O
X O
- O
linked O
recessive O
disorder O
characterized O
by O
a O
broad O
spectrum O
of O
clinical O
features O
including O
cardiac O
and O
skeletal O
myopathy O
, O
neutropenia O
, O
exercise O
intolerance O
, O
and O
growth O
delay O
. O
Most O
affected O
patients O
are O
diagnosed O
during O
childhood O
, O
and O
mortality O
is O
highest O
in O
the O
first O
years O
of O
life O
. O
As O
a O
consequence O
, O
Barth O
syndrome O
is O
often O
considered O
a O
paediatric O
disease O
. O
Here O
, O
we O
report O
a O
case O
where O
the O
diagnosis O
was O
established O
in O
a O
39 O
- O
year O
- O
old O
patient O
with O
left O
ventricular O
non O
- O
compaction O
and O
neutropenia O
. O
The O
clinical O
course O
of O
the O
patient O
presented O
here O
was O
relatively O
benign O
. O
This O
suggests O
that O
the O
prevalence B-EPI
of O
Barth O
syndrome O
in O
adults O
may O
be O
underestimated O
. O
Barth O
syndrome O
should O
be O
considered O
in O
the O
differential O
diagnosis O
of O
male O
patients O
with O
cardiomyopathy O
and O
neutropenia O
. O
The O
Arab O
population O
encompasses O
over O
420 O
million O
people O
characterized O
by O
genetic O
admixture O
and O
a O
consequent O
rich O
genetic O
diversity O
. O
A O
number O
of O
genetic O
diseases O
have O
been O
reported O
for O
the O
first O
time O
from O
the O
population O
. O
Additionally O
a O
high O
prevalence B-EPI
of O
some O
genetic O
diseases O
including O
autosomal O
recessive O
disorders O
such O
as O
hemoglobinopathies O
and O
familial O
mediterranean O
fever O
have O
been O
found O
in O
the O
population O
and O
across O
the O
region O
. O
There O
is O
a O
paucity O
of O
databases O
cataloguing O
genetic O
variants O
of O
clinical O
relevance O
from O
the O
population O
. O
The O
availability O
of O
such O
a O
catalog O
could O
have O
implications O
in O
precise O
diagnosis O
, O
genetic O
epidemiology O
and O
prevention O
of O
disease O
. O
To O
fill O
in O
the O
gap O
, O
we O
have O
compiled O
DALIA O
, O
a O
comprehensive O
compendium O
of O
genetic O
variants O
reported O
in O
literature O
and O
implicated O
in O
genetic O
diseases O
reported O
from O
the O
Arab O
population O
. O
The O
database O
aims O
to O
act O
as O
an O
effective O
resource O
for O
population O
- O
scale O
and O
sub O
- O
population O
specific O
variant O
analyses O
, O
enabling O
a O
ready O
reference O
aiding O
clinical O
interpretation O
of O
genetic O
variants O
, O
genetic O
epidemiology O
, O
as O
well O
as O
facilitating O
rapid O
screening O
and O
a O
quick O
reference O
for O
evaluating O
evidence O
on O
genetic O
diseases O
. O
Purpose O
VACTERL O
association O
is O
a O
rare O
and O
complex O
condition O
of O
congenital O
malformations O
, O
often O
requiring O
repeated O
surgery O
and O
entailing O
various O
physical O
sequelae O
. O
Due O
to O
scarcity O
of O
knowledge O
, O
the O
study O
aim O
was O
to O
investigate O
self O
- O
reported O
health O
- O
related O
quality O
of O
life O
( O
HRQoL O
) O
, O
anxiety O
, O
depression O
and O
self O
- O
concept O
in O
children O
and O
adolescents O
with O
VACTERL O
association O
and O
self O
- O
reported O
anxiety O
and O
depression O
in O
their O
parents O
. O
Methods O
Patients O
aged O
8 O
- O
17 O
years O
with O
VACTERL O
association O
and O
their O
parents O
were O
recruited O
from O
three O
of O
four O
Swedish O
paediatric O
surgical O
centres O
during O
2015 O
- O
2019 O
. O
The O
well O
- O
established O
validated O
questionnaires O
DISABKIDS O
, O
Beck O
Youth O
Inventories O
, O
Beck O
Anxiety O
Inventory O
and O
Beck O
Depression O
Inventory O
were O
sent O
to O
the O
families O
. O
Data O
were O
analysed O
using O
descriptives O
, O
t O
tests O
and O
multivariable O
analysis O
. O
Results O
were O
compared O
with O
norm O
groups O
and O
reference O
samples O
. O
Results O
The O
questionnaires O
were O
returned O
by O
40 O
patients O
, O
38 O
mothers O
and O
33 O
fathers O
. O
The O
mean O
HRQoL O
was O
M O
= O
80.4 O
, O
comparable O
to O
children O
with O
asthma O
( O
M O
= O
80.2 O
) O
and O
diabetes O
( O
M O
= O
79.5 O
) O
. O
Self O
- O
reported O
psychological O
well O
- O
being O
was O
comparable O
to O
the O
norm O
group O
of O
Swedish O
school O
children O
, O
and O
was O
significantly O
higher O
than O
a O
clinical O
sample O
. O
Factors O
negatively O
influencing O
children O
's O
HRQoL O
and O
psychological O
well O
- O
being O
were O
identified O
. O
The O
parents O
' O
self O
- O
reports O
of O
anxiety O
and O
depression O
were O
comparable O
to O
non O
- O
clinical O
samples O
. O
Conclusions O
Although O
children O
and O
adolescents O
with O
VACTERL O
association O
reported O
similar O
HRQoL O
to O
those O
of O
European O
children O
with O
chronic O
conditions O
, O
their O
psychological O
well O
- O
being O
was O
comparable O
to O
Swedish O
school O
children O
in O
general O
. O
Nevertheless O
, O
some O
individuals O
among O
both O
children O
and O
parents O
were O
in O
need O
of O
extra O
support O
. O
This O
attained O
knowledge O
is O
valuable O
when O
counselling O
parents O
regarding O
the O
prognosis O
for O
children O
with O
VACTERL O
association O
. O
The O
mermaid O
syndrome O
( O
sirenomelia O
) O
is O
an O
extremely O
rare O
anomaly O
, O
an O
incidence B-EPI
of O
1 O
in O
100,000 O
births O
, O
in O
which O
a O
newborn O
born O
with O
legs O
joined O
together O
featuring O
a O
mermaid O
- O
like O
appearance O
( O
head O
and O
trunk O
like O
humans O
and O
tail O
like O
fish O
) O
, O
and O
in O
most O
cases O
die O
shortly O
after O
birth O
. O
Gastrointestinal O
and O
urogenital O
anomalies O
and O
single O
umbilical O
artery O
are O
clinical O
outcome O
of O
this O
syndrome O
. O
There O
are O
two O
important O
hypotheses O
for O
pathogenesis O
of O
mermaid O
syndrome O
: O
vitelline O
artery O
steal O
hypothesis O
and O
defective O
blastogenesis O
hypothesis O
. O
The O
cause O
of O
the O
mermaid O
syndrome O
is O
unknown O
, O
but O
there O
are O
some O
possible O
factors O
such O
as O
age O
younger O
than O
20 O
years O
and O
older O
than O
40 O
years O
in O
mother O
and O
exposure O
of O
fetus O
to O
teratogenics O
. O
Here O
, O
we O
introduced O
19 O
- O
year O
- O
old O
mother O
's O
first O
neonate O
with O
mermaid O
syndrome O
. O
The O
mother O
had O
gestational O
diabetes O
mellitus O
and O
neonate O
was O
born O
with O
single O
lower O
limb O
, O
ambiguous O
genitalia O
, O
and O
thumb O
anomalies O
, O
and O
4 O
days O
after O
birth O
, O
the O
neonate O
died O
due O
to O
multiple O
anomalies O
and O
imperforated O
anus O
. O
The O
use O
of O
proton O
pump O
inhibitors O
( O
PPIs O
) O
over O
the O
last O
30 O
years O
has O
rapidly O
increased O
both O
in O
the B-LOC
United I-LOC
States I-LOC
and O
worldwide B-LOC
. O
PPIs O
are O
not O
only O
very O
widely O
used O
both O
for O
approved O
indications O
( O
peptic O
ulcer O
disease O
, O
gastroesophageal O
reflux O
disease O
( O
GERD O
) O
, O
Helicobacter O
pylori O
eradication O
regimens O
, O
stress O
ulcer O
prevention O
) O
, O
but O
are O
also O
one O
of O
the O
most O
frequently O
off O
- O
label O
used O
drugs O
( O
25 B-STAT
- O
70 O
% O
of O
total O
) O
. O
An O
increasing O
number O
of O
patients O
with O
moderate O
to O
advanced O
gastroesophageal O
reflux O
disease O
are O
remaining O
on O
PPI O
indefinitely O
. O
Whereas O
numerous O
studies O
show O
PPIs O
remain O
effective O
and O
safe O
, O
most O
of O
these O
studies O
are O
< O
5 O
years O
of O
duration O
and O
little O
data O
exist O
for O
> O
10 O
years O
of O
treatment O
. O
Recently O
, O
based O
primarily O
on O
observational O
/ O
epidemiological O
studies O
, O
there O
have O
been O
an O
increasing O
number O
of O
reports O
raising O
issues O
about O
safety O
and O
side O
- O
effects O
with O
very O
long O
- O
term O
chronic O
treatment O
. O
Some O
of O
these O
safety O
issues O
are O
related O
to O
the O
possible O
long O
- O
term O
effects O
of O
chronic O
hypergastrinemia O
, O
which O
occurs B-EPI
in O
all O
patients O
taking O
chronic O
PPIs O
, O
others O
are O
related O
to O
the O
hypo-/achlorhydria O
that O
frequently O
occurs B-EPI
with O
chronic O
PPI O
treatment O
, O
and O
in O
others O
the O
mechanisms O
are O
unclear O
. O
These O
issues O
have O
raised O
considerable O
controversy O
in O
large O
part O
because O
of O
lack O
of O
long O
- O
term O
PPI O
treatment O
data O
( O
> O
10 O
- O
20 O
years O
) O
. O
Zollinger O
- O
Ellison O
syndrome O
( O
ZES O
) O
is O
caused O
by O
ectopic O
secretion O
of O
gastrin O
from O
a O
neuroendocrine O
tumor O
resulting O
in O
severe O
acid O
hypersecretion O
requiring O
life O
- O
long O
antisecretory O
treatment O
with O
PPIs O
, O
which O
are O
the O
drugs O
of O
choice O
. O
Because O
in O
< O
30 O
% O
of O
patients O
with O
ZES O
, O
a O
long O
- O
term O
cure O
is O
not O
possible O
, O
these O
patients O
have O
life O
- O
long O
hypergastrinemia O
and O
require O
life O
- O
long O
treatment O
with O
PPIs O
. O
Therefore O
, O
ZES O
patients O
have O
been O
proposed O
as O
a O
good O
model O
of O
the O
long O
- O
term O
effects O
of O
hypergastrinemia O
in O
man O
as O
well O
as O
the O
effects O
/ O
side O
- O
effects O
of O
very O
long O
- O
term O
PPI O
treatment O
. O
In O
this O
article O
, O
the O
insights O
from O
studies O
on O
ZES O
into O
these O
controversial O
issues O
with O
pertinence O
to O
chronic O
PPI O
use O
in O
non B-LOC
- I-LOC
ZES I-LOC
patients O
is O
reviewed O
, O
primarily O
concentrating O
on O
data O
from O
the O
prospective O
long O
- O
term O
studies O
of O
ZES O
patients O
at O
NIH O
. O
Aarskog O
- O
Scott O
syndrome O
is O
a O
genetically O
and O
clinically O
heterogeneous O
rare O
condition O
caused O
by O
a O
pathogenic O
variant O
in O
the O
FGD1 O
gene O
. O
A O
systematic O
review O
was O
carried O
out O
to O
analyse O
the O
prevalence B-EPI
of O
clinical O
manifestations O
found O
in O
patients O
, O
as O
well O
as O
to O
evaluate O
the O
genotype O
- O
phenotype O
correlation O
. O
The O
results O
obtained O
show O
that O
clinical O
findings O
of O
the O
craniofacial O
, O
orthopaedic O
, O
and O
genitourinary O
tract O
correspond O
to O
the O
highest O
scores O
of O
prevalence B-EPI
. O
The O
authors O
reclassified O
the O
primary O
, O
secondary O
, O
and O
additional O
criteria O
based O
on O
their O
prevalence B-EPI
. O
Furthermore O
, O
it O
was O
possible O
to O
observe O
, O
in O
accordance O
with O
previous O
reports O
, O
that O
the O
reported O
phenotypes O
do O
not O
present O
a O
direct O
relation O
to O
the O
underlying O
genotypes O
. O
This O
study O
aims O
to O
identify O
the O
baseline O
patient O
characteristics O
, O
clinical O
presentation O
, O
and O
response O
to O
treatment O
of O
11 O
patients O
who O
were O
diagnosed O
with O
thrombotic O
thrombocytopenic O
purpura O
( O
TTP O
) O
between O
2014 O
and O
2020 O
at O
Brookdale O
University O
Hospital O
Medical O
Center O
, O
Brooklyn B-LOC
, O
NY B-LOC
. O
Laboratory O
and O
clinical O
parameters O
were O
recorded O
for O
29 O
patients O
who O
received O
plasmapheresis O
in O
this O
time O
period O
. O
Of O
29 O
patients O
, O
11 O
had O
confirmed O
TTP O
and O
one O
was O
diagnosed O
with O
hereditary O
TTP O
. O
Young O
, O
black O
, O
and O
female O
patients O
made O
up O
the O
majority O
of O
our O
patient O
population O
. O
A O
high O
prevalence B-EPI
of O
obesity O
and O
drug O
abuse O
were O
seen O
among O
our O
patients O
. O
Five O
out O
of O
11 O
were O
obese O
and O
four O
of O
them O
were O
morbidly O
obese O
; O
six O
out O
of O
11 O
patients O
were O
positive O
for O
the O
drug O
screen O
including O
cannabinoids O
( O
3 O
) O
, O
opiates O
( O
2 O
) O
, O
benzodiazepines O
( O
1 O
) O
, O
PCP O
( O
1 O
) O
, O
and O
methadone O
( O
1 O
) O
. O
Four O
patients O
with O
a O
positive O
drug O
screen O
had O
acute O
kidney O
injury O
( O
AKI O
) O
, O
and O
plasmapheresis O
helped O
them O
enhance O
their O
kidney O
function O
. O
We O
observed O
a O
high O
incidence B-EPI
of O
AKI O
and O
high O
TTP O
exacerbation O
rates O
in O
patients O
who O
were O
drug O
abusers O
and O
those O
who O
were O
morbidly O
obese O
. O
There O
is O
a O
paucity O
of O
data O
on O
the O
relationship O
of O
TTP O
with O
obesityor O
drug O
abuse O
and O
this O
needs O
further O
study O
. O
Background O
Gastric O
enterochromaffin O
- O
like O
cell O
( O
ECL O
) O
tumours O
can O
occur O
in O
patients O
with O
multiple O
endocrine O
neoplasia O
type O
1 O
( O
MEN1 O
) O
, O
especially O
in O
those O
affected O
by O
Zollinger O
Ellison O
syndrome O
( O
ZES O
) O
. O
Since O
the O
prevalence B-EPI
of O
ECL O
lesions O
is O
not O
well O
defined O
yet O
, O
the O
present O
study O
evaluated O
the O
presence O
and O
extent O
of O
ECL O
lesions O
in O
MEN1 O
patients O
with O
and O
without O
ZES O
. O
Methods O
Multiple O
endocrine O
neoplasia O
type O
1 O
patients O
being O
part O
of O
a O
regular O
screening O
program O
( O
2014 O
- O
2018 O
) O
underwent O
gastroduodenoscopies O
with O
biopsies O
of O
the O
stomach O
and O
determination O
of O
serum O
gastrin O
and O
chromogranin O
A O
levels O
. O
Haematoxylin- O
and O
immunostaining O
with O
chromogranin O
A O
, O
gastrin O
and O
VMAT O
I O
and O
II O
( O
vesicular O
monoamine O
transporter O
I O
and O
II O
) O
of O
the O
biopsies O
were O
performed O
. O
Results O
Thirty O
- O
eight O
MEN1 O
patients O
, O
of O
whom O
16 B-STAT
( O
42 O
% O
) O
were O
diagnosed O
and O
treated O
earlier O
for O
ZES O
, O
were O
analysed O
. O
In O
ten O
of O
16 B-STAT
( O
62.5 O
% O
) O
ZES O
patients O
, O
a O
locally O
scattered O
, O
mixed O
image O
of O
diffuse O
, O
linear O
and O
micronodular O
mild O
hyperplasia O
was O
present O
. O
In O
addition O
, O
two O
of O
these O
patients O
( O
13 O
% O
) O
showed O
small O
( O
max O
1.5 O
mm O
in O
size O
) O
intramucosal O
ECL O
tumours O
. O
Neither O
ECL O
changes O
, O
nor O
tumours O
were O
found O
in O
MEN1 O
patients O
without O
ZES O
( O
n O
= O
22 O
) O
. O
In O
MEN1 O
/ O
ZES O
patients O
, O
the O
median O
serum O
gastrin O
level O
was O
significantly O
elevated O
compared O
to O
MEN1 O
patients O
without O
ZES O
( O
206 O
pg O
/ O
ml O
vs. O
30.5 O
pg O
/ O
ml O
, O
p O
< O
.001 O
) O
. O
A O
subgroup O
analysis O
of O
the O
serum O
gastrin O
and O
chromogranin O
A O
levels O
of O
MEN1 O
/ O
ZES O
patients O
with O
or O
without O
ECL O
hyperplasia O
did O
not O
show O
significant O
differences O
( O
gastrin O
level O
: O
p O
= O
.302 O
, O
chromogranin O
A O
: O
p O
= O
.464 O
) O
. O
Conclusion O
Enterochromaffin O
- O
like O
cell O
hyperplasia O
and O
gastric O
carcinoids O
occur O
only O
in O
MEN1 O
patients O
with O
ZES O
, O
but O
less O
frequently O
than O
reported O
. O
The O
Dandy O
- O
Walker O
Malformation O
was O
first O
described O
in O
1914 O
by O
Dandy O
and O
Blackfan O
and O
is O
characterized O
by O
hypoplasia O
of O
the O
vermis O
, O
pseudocystic O
fourth O
ventricle O
, O
upward O
displacement O
of O
the O
tentorium O
, O
torcular O
and O
lateral O
sinuses O
, O
and O
anteroposterior O
enlargement O
of O
the O
posterior O
fossa O
. O
This O
syndrome O
commonly O
manifests O
as O
hydrocephalus O
in O
children O
, O
though O
rare O
adult O
cases O
have O
been O
reported O
. O
The O
literature O
reveals O
adult O
symptomatology O
including O
brainstem O
infarction O
, O
psychosis O
, O
and O
neuromuscular O
disease O
. O
Stroke O
is O
an O
exceptionally O
rare O
presentation O
of O
this O
malformation O
, O
with O
only O
one O
ischemic O
event O
reported O
in O
the O
literature O
. O
This O
case O
offers O
a O
rare O
opportunity O
for O
diagnosis O
in O
an O
adult O
presenting O
with O
a O
hemorrhagic O
stroke O
of O
the O
basal O
ganglia O
in O
an O
otherwise O
asymptomatic O
young O
adult O
male O
. O
To O
the O
best O
of O
our O
knowledge O
, O
this O
is O
the O
first O
reported O
case O
of O
a O
hemorrhagic O
stroke O
in O
an O
adult O
patient O
with O
Dandy O
- O
Walker O
Malformation O
. O
Hypertrophic O
cardiomyopathy O
( O
HCM O
) O
is O
a O
myocardial O
disease O
characterized O
by O
left O
ventricular O
hypertrophy O
not O
solely O
explained O
by O
abnormal O
loading O
conditions O
. O
Despite O
its O
rare O
prevalence B-EPI
in O
pediatric O
age O
, O
HCM O
carries O
a O
relevant O
risk O
of O
mortality O
and O
morbidity O
in O
both O
infants O
and O
children O
. O
Pediatric O
HCM O
is O
a O
large O
heterogeneous O
group O
of O
disorders O
. O
Other O
than O
mutations O
in O
sarcomeric O
genes O
, O
which O
represent O
the O
most O
important O
cause O
of O
HCM O
in O
adults O
, O
childhood O
HCM O
includes O
a O
high O
prevalence B-EPI
of O
non O
- O
sarcomeric O
causes O
, O
including O
inherited O
errors O
of O
metabolism O
( O
i.e. O
, O
glycogen O
storage O
diseases O
, O
lysosomal O
storage O
diseases O
, O
and O
fatty O
acid O
oxidation O
disorders O
) O
, O
malformation O
syndromes O
, O
neuromuscular O
diseases O
, O
and O
mitochondrial O
disease O
, O
which O
globally O
represent O
up O
to O
35 B-STAT
% O
of O
children O
with O
HCM O
. O
The O
age O
of O
presentation O
and O
the O
underlying O
etiology O
significantly O
impact O
the O
prognosis O
of O
children O
with O
HCM O
. O
Moreover O
, O
in O
recent O
years O
, O
different O
targeted O
approaches O
for O
non O
- O
sarcomeric O
etiologies O
of O
HCM O
have O
emerged O
. O
Therefore O
, O
the O
etiological O
diagnosis O
is O
a O
fundamental O
step O
in O
designing O
specific O
management O
and O
therapy O
in O
these O
subjects O
. O
The O
present O
review O
aims O
to O
provide O
an O
overview O
of O
the O
non O
- O
sarcomeric O
causes O
of O
HCM O
in O
children O
, O
focusing O
on O
the O
pathophysiology O
, O
clinical O
features O
, O
diagnosis O
, O
and O
treatment O
of O
these O
rare O
disorders O
. O
Background O
and O
Objectives O
: O
This O
is O
the O
first O
study O
assessing O
risk O
factors O
for O
cerebral O
palsy O
( O
CP O
) O
among O
children O
born O
in O
Moldova B-LOC
. O
The O
aim O
of O
this O
study O
was O
to O
identify O
and O
describe O
risk O
factors O
for O
cerebral O
palsy O
( O
CP O
) O
among O
children O
born O
in O
Moldova B-LOC
, O
which O
is O
one O
of O
the O
low O
- O
middle O
income O
countries O
in O
Europe B-LOC
. O
Materials O
and O
Methods O
: O
We O
identified O
351 O
children O
with O
CP O
born O
during O
2009 O
and O
2010 O
in O
Moldova B-LOC
. O
Detailed O
information O
on O
417 O
children O
without O
CP O
served O
as O
a O
reference O
group O
. O
Logistic O
regression O
analyses O
were O
applied O
to O
the O
calculate O
crude O
and O
adjusted O
odds O
ratios O
( O
OR O
) O
for O
CP O
with O
95 O
% O
confidence O
intervals O
( O
CI O
) O
in O
addition O
to O
attributable O
fraction O
( O
AF O
) O
. O
Results O
: O
Among O
children O
with O
CP O
( O
40.5 O
% O
girls O
) O
, O
26 O
% O
had O
spastic O
unilateral O
, O
54 O
% O
bilateral O
, O
13 O
% O
dyskinetic O
, O
5 O
% O
ataxic O
and O
2 O
% O
unclassified O
CP O
. O
Significant O
risk O
factors O
for O
CP O
included O
maternal O
alcohol O
consumption O
during O
pregnancy O
( O
OR O
1.7 O
, O
p O
= O
0.002 O
) O
, O
maternal O
hypertension O
( O
OR O
2.0 O
, O
p O
< O
0.001 O
) O
, O
children O
born O
to O
mothers O
from O
the O
rural O
areas O
( O
OR O
1.6 O
, O
p O
< O
0.001 O
) O
, O
maternal O
age O
≥35 O
years O
( O
OR O
0.6 O
, O
p O
= O
0.018 O
) O
, O
maternal O
epilepsy O
( O
OR O
4.3 O
, O
p O
< O
0.001 O
) O
, O
breech O
delivery O
( O
OR O
3.1 O
, O
p O
= O
0.001 O
) O
, O
home O
births O
( O
OR O
6.3 O
, O
p O
= O
0.001 O
) O
, O
umbilical O
cord O
around O
neck O
( O
OR O
2.2 O
, O
p O
< O
0.001 O
) O
, O
AVD O
( O
OR O
3.1 O
, O
p O
< O
0.001 O
) O
, O
male O
gender O
( O
OR O
1.3 O
, O
p O
< O
0.001 O
) O
, O
SGA O
( O
OR O
1.3 O
, O
p O
= O
0.027 O
) O
, O
multiple O
gestations O
( O
OR O
1.7 O
, O
p O
< O
0.001 O
) O
and O
hyperbilirubinemia O
( O
OR O
4.5 O
, O
p O
< O
0.001 O
) O
. O
Multivariable O
analyses O
showed O
that O
the O
AF O
of O
CP O
was O
64 O
% O
for O
rural O
residence O
( O
OR O
2.8 O
, O
p O
= O
0.002 O
) O
, O
87 O
% O
for O
home O
birth O
( O
7.6 O
, O
p O
= O
0.005 O
) O
, O
79 O
% O
for O
pre O
- O
labor O
rupture O
of O
membrane O
( O
OR O
4.9 O
, O
p O
= O
0.001 O
) O
, O
66 O
% O
for O
breech O
delivery O
( O
OR O
2.9 O
, O
p O
= O
0.002 O
) O
and O
81 O
% O
for O
hyperbilirubinemia O
( O
OR O
5.4 O
, O
p O
< O
0.001 O
) O
. O
Conclusions O
: O
A O
combination O
of O
factors O
related O
to O
the O
mother O
, O
the O
delivery O
and O
the O
child O
were O
risk O
factors O
for O
CP O
in O
Moldova B-LOC
, O
many O
of O
them O
possibly O
avoidable O
. O
Improved O
pregnancy O
and O
maternity O
care O
would O
potentially O
reduce O
the O
risk O
of O
CP O
. O
A O
national O
CP O
registry O
in O
Moldova B-LOC
is O
suggested O
as O
an O
opportunity O
to O
follow O
up O
on O
these O
findings O
. O
Usher O
syndrome O
, O
the O
most O
prevalent B-EPI
cause O
of O
combined O
hereditary O
vision O
and O
hearing O
impairment O
, O
is O
clinically O
and O
genetically O
heterogeneous O
. O
Moreover O
, O
several O
conditions O
with O
phenotypes O
overlapping O
Usher O
syndrome O
have O
been O
described O
. O
This O
makes O
the O
molecular O
diagnosis O
of O
hereditary O
deaf O
- O
blindness O
challenging O
. O
Here O
, O
we O
performed O
exome O
sequencing O
and O
analysis O
on O
7 O
Mexican O
and O
52 O
Iranian O
probands O
with O
combined O
retinal O
degeneration O
and O
hearing O
impairment O
( O
without O
intellectual O
disability O
) O
. O
Clinical O
assessment O
involved O
ophthalmological O
examination O
and O
hearing O
loss O
questionnaire O
. O
Usher O
syndrome O
, O
most O
frequently O
due O
to O
biallelic O
variants O
in O
MYO7A O
( O
USH1B O
in O
16 O
probands O
) O
, O
USH2A O
( O
17 O
probands O
) O
, O
and O
ADGRV1 O
( O
USH2C O
in O
7 O
probands O
) O
, O
was O
diagnosed O
in O
44 O
of O
59 B-STAT
( O
75 O
% O
) O
unrelated O
probands O
. O
Almost O
half O
of O
the O
identified O
variants O
were O
novel O
. O
Nine O
of O
59 B-STAT
( O
15 O
% O
) O
probands O
displayed O
other O
genetic O
entities O
with O
dual O
sensory O
impairment O
, O
including O
Alström O
syndrome O
( O
3 O
patients O
) O
, O
cone O
- O
rod O
dystrophy O
and O
hearing O
loss O
1 B-STAT
( I-STAT
2 I-STAT
probands O
) O
, O
and O
Heimler O
syndrome O
( O
1 O
patient O
) O
. O
Unexpected O
findings O
included O
one O
proband O
each O
with O
Scheie O
syndrome O
, O
coenzyme O
Q10 O
deficiency O
, O
and O
pseudoxanthoma O
elasticum O
. O
In O
four O
probands O
, O
including O
three O
Usher O
cases O
, O
dual O
sensory O
impairment O
was O
either O
modified O
/ O
aggravated O
or O
caused O
by O
variants O
in O
distinct O
genes O
associated O
with O
retinal O
degeneration O
and/or O
hearing O
loss O
. O
The O
overall O
diagnostic O
yield O
of O
whole O
exome O
analysis O
in O
our O
deaf O
- O
blind O
cohort O
was O
92 B-STAT
% I-STAT
. O
Two O
( O
3 O
% O
) O
probands O
were O
partially O
solved O
and O
only O
3 B-STAT
( O
5 O
% O
) O
remained O
without O
any O
molecular O
diagnosis O
. O
In O
many O
cases O
, O
the O
molecular O
diagnosis O
is O
important O
to O
guide O
genetic O
counseling O
, O
to O
support O
prognostic O
outcomes O
and O
decisions O
with O
currently O
available O
and O
evolving O
treatment O
modalities O
. O
Introduction O
We O
investigated O
the O
prevalence B-EPI
of O
human O
T O
- O
cell O
lymphotropic O
virus O
types O
1 B-STAT
and I-STAT
2 I-STAT
( O
HTLV-1/2 O
) O
infection O
in O
patients O
with O
hematological O
diseases O
from O
the O
western O
Amazon O
region O
of O
Brazil B-LOC
. O
Methods O
Samples O
from O
306 O
patients O
were O
submitted O
for O
the O
molecular O
diagnosis O
of O
HTLV-1/2 O
infection O
by O
real O
time O
PCR O
( O
qPCR O
) O
, O
with O
amplification O
, O
sequencing O
, O
and O
phylogenetic O
analysis O
of O
the O
long O
terminal O
repeat O
( O
LTR O
) O
region O
. O
Results O
A O
29 O
- O
year O
- O
old O
male O
carrier O
of O
sickle O
cell O
anemia O
with O
a O
history O
of O
multiple O
blood O
transfusions O
was O
diagnosed O
with O
the O
HTLV-2c O
subtype O
. O
Conclusions O
This O
study O
describes O
the O
first O
known O
occurrence B-EPI
of O
HTLV-2c O
in O
the O
urban O
area O
of O
Brazil B-LOC
's O
western O
Amazon O
region O
. O
Background O
Vitiligo O
is O
a O
disfiguring O
skin O
disease O
with O
profound O
psychosocial O
impacts O
, O
such O
as O
anxiety O
, O
but O
the O
reported O
effect O
sizes O
of O
associations O
vary O
. O
We O
aimed O
to O
conduct O
a O
meta O
- O
analysis O
to O
quantify O
the O
strength O
of O
association O
between O
anxiety O
and O
vitiligo O
and O
to O
estimate O
the O
prevalence B-EPI
of O
anxiety O
among O
individuals O
with O
vitiligo O
. O
Methods O
A O
systematic O
literature O
search O
was O
performed O
in O
five O
online O
databases O
( O
MEDLINE O
, O
Embase O
, O
Web O
of O
Science O
, O
Cochrane O
Library O
, O
and O
PsycINFO O
) O
from O
inception O
until O
March O
20 O
, O
2020 O
. O
All O
of O
the O
eligible O
studies O
were O
comprehensively O
reviewed O
, O
and O
all O
of O
the O
available O
data O
were O
analyzed O
according O
to O
our O
predefined O
criteria O
. O
Results O
Twenty B-STAT
- I-STAT
one I-STAT
studies I-STAT
involving I-STAT
3259 I-STAT
patients O
in O
11 O
countries O
were O
included O
in O
this O
meta O
- O
analysis O
. O
Compared O
with O
the O
healthy O
control O
group O
, O
patients O
with O
vitiligo O
often O
had O
concomitant O
anxiety O
( O
OR O
= O
6.14 O
[ O
95 O
% O
CI O
: O
3.35 O
- O
11.24 O
] O
, O
I O
2 B-STAT
= O
30.1 O
% O
) O
. O
The O
pooled B-EPI
prevalence I-EPI
of O
anxiety O
in O
female O
patients O
was O
significantly O
higher O
than O
that O
in O
males O
( O
OR O
= O
2.24 O
[ O
95 O
% O
CI O
: O
1.31 O
- O
3.84 O
] O
, O
I O
2 B-STAT
= I-STAT
0.0 I-STAT
% I-STAT
) O
. O
Subgroup O
analysis O
showed O
that O
the O
pooled B-EPI
prevalence I-EPI
of O
clinical O
anxiety O
disorder O
and O
anxiety O
symptoms O
was O
12 O
% O
( O
95 O
% O
CI O
: O
7%-16 O
% O
, O
I O
2 B-STAT
= O
76.3 O
% O
) O
and O
34 O
% O
( O
95 O
% O
CI O
: O
21%-46 O
% O
, O
I O
2 B-STAT
= O
94.7 O
% O
) O
, O
respectively O
. O
No O
publication O
bias O
has O
been O
detected O
by O
Begg O
's O
funnel O
plot O
and O
Egger O
's O
test O
. O
Conclusion O
Patients O
with O
vitiligo O
have O
high O
anxiety O
comorbidity O
, O
with O
female O
predominance O
. O
Dermatologists O
and O
psychiatrists O
should O
be O
vigilant O
to O
the O
presence O
of O
anxiety O
, O
apply O
appropriate O
interventions O
to O
reduce O
the O
psychological O
impacts O
in O
a O
timely O
manner O
, O
and O
thus O
promote O
recovery O
in O
vitiligo O
patients O
. O
However O
, O
due O
to O
some O
objective O
limitations O
( O
poor O
information O
about O
the O
OR O
and O
diversity O
in O
assessment O
tools O
among O
included O
studies O
) O
, O
findings O
should O
be O
interpreted O
with O
caution O
. O
Congenital O
hepatic O
fibrosis O
( O
CHF O
) O
is O
a O
rare O
autosomal O
recessive O
disease O
derived O
from O
biliary O
dysgenesis O
secondary O
to O
ductal O
plate O
malformation O
; O
it O
often O
coexists O
with O
Caroli O
's O
disease O
, O
von O
Meyenburg O
complexes O
, O
autosomal O
dominant O
polycystic O
kidney O
disease O
( O
ADPKD O
) O
, O
and O
autosomal O
recessive O
polycystic O
kidney O
disease O
( O
ARPKD O
) O
. O
Although O
CHF O
was O
first O
named O
and O
described O
in O
detail O
by O
Kerr O
et O
al O
. O
in O
1961 O
. O
Its O
pathogenesis O
still O
remains O
unclear O
. O
The O
exact O
incidence B-EPI
and O
prevalence B-EPI
are O
not O
known O
, O
and O
only O
a O
few O
hundred O
patients O
with O
CHF O
have O
been O
reported O
in O
the O
literature O
to O
date O
. O
However O
, O
with O
the O
development O
of O
noninvasive O
diagnostic O
techniques O
such O
as O
ultrasound O
, O
computed O
tomography O
( O
CT O
) O
, O
and O
magnetic O
resonance O
imaging O
( O
MRI O
) O
, O
CHF O
may O
now O
be O
more O
frequently O
detected O
. O
Anatomopathological O
examination O
of O
liver O
biopsy O
is O
the O
gold O
standard O
in O
diagnosis O
of O
CHF O
. O
Patients O
with O
CHF O
exhibit O
variable O
clinical O
presentations O
, O
ranging O
from O
no O
symptoms O
to O
severe O
symptoms O
such O
as O
acute O
hepatic O
decompensation O
and O
even O
cirrhosis O
. O
The O
most O
common O
presentations O
in O
these O
patients O
are O
splenomegaly O
, O
esophageal O
varices O
, O
and O
gastrointestinal O
bleeding O
due O
to O
portal O
hypertension O
. O
In O
addition O
, O
in O
younger O
children O
, O
CHF O
often O
is O
accompanied O
by O
renal O
cysts O
or O
increased O
renal O
echogenicity O
. O
Great O
variability O
exists O
among O
the O
signs O
and O
symptoms O
of O
the O
disease O
from O
early O
childhood O
to O
the O
5 O
th O
or O
6 O
th O
decade O
of O
life O
, O
and O
in O
most O
patients O
the O
disorder O
is O
diagnosed O
during O
adolescence O
or O
young O
adulthood O
. O
Here O
, O
we O
present O
two O
cases O
of O
congenital O
hepatic O
fibrosis O
in O
2 O
- O
years O
- O
old O
girl O
and O
12 O
- O
year O
- O
old O
male O
who O
had O
been O
referred O
for O
evaluation O
of O
an O
abdominal O
distension O
with O
persistent O
hyper O
- O
transaminasemia O
and O
cholestasis O
, O
the O
diagnostic O
was O
made O
according O
to O
the O
results O
of O
medical O
imaging O
( O
CT O
or O
MRI O
) O
, O
a O
liver O
biopsy O
, O
and O
genetic O
testing O
. O
BACKGROUND O
: O
Balanced O
reciprocal O
chromosomal O
translocations O
( O
RCTs O
) O
are O
the O
ones O
of O
the O
most O
common O
structural O
aberrations O
in O
the O
population O
, O
with O
an O
incidence B-EPI
of O
1:625 O
. O
RCT O
carriers O
usually O
do O
not O
demonstrate O
changes O
in O
phenotype O
, O
except O
when O
the O
translocation O
results O
in O
gene O
interruption O
. O
However O
, O
these O
people O
are O
at O
risk O
of O
production O
of O
unbalanced O
gametes O
during O
meiosis O
, O
as O
a O
result O
of O
various O
forms O
of O
chromosome O
segregation O
. O
This O
may O
cause O
infertility O
, O
non O
- O
implantation O
of O
the O
embryo O
, O
shorter O
embryo O
or O
foetus O
survival O
, O
as O
well O
as O
congenital O
defects O
and O
developmental O
disorders O
in O
children O
after O
birth O
. O
The O
increasing O
popularity O
of O
cytogenetic O
molecular O
techniques O
, O
such O
as O
microarray O
- O
based O
CGH O
( O
aCGH O
) O
, O
contributed O
to O
the O
improved O
detection O
of O
chromosomal O
abnormalities O
in O
patients O
with O
intellectual O
disability O
, O
however O
, O
these O
modern O
techniques O
do O
not O
allow O
the O
identification O
of O
the O
balanced O
in O
potential O
carriers O
. O
Therefore O
, O
classical O
chromosome O
analysis O
with O
GTG O
technique O
still O
plays O
an O
important O
role O
in O
the O
identification O
of O
balanced O
rearrangements O
in O
every O
case O
of O
procreation O
failure O
. O
CASE O
PRESENTATION O
: O
In O
this O
article O
, O
a O
family O
with O
multiple O
occurrences B-EPI
of O
17p13.3 O
duplication O
syndrome O
in O
the O
offspring O
and O
multiple O
miscarriages O
resulting O
from O
carrying O
of O
the O
balanced O
reciprocal O
translocation O
t(7;17)(p22;p13.2 O
) O
by O
proband O
father O
is O
presented O
. O
The O
aCGH O
diagnostics O
allowed O
the O
identification O
of O
an O
unbalanced O
fragment O
responsible O
for O
the O
occurrence B-EPI
of O
clinical O
signs O
in O
the O
female O
patient O
, O
while O
karyotyping O
and O
FISH O
using O
specific O
probes O
allowed O
the O
localization O
of O
the O
additional O
material O
in O
the O
patient O
chromosomes O
, O
and O
identified O
the O
type O
of O
this O
translocation O
in O
the O
carriers O
. O
CONCLUSIONS O
: O
Identification O
of O
a O
balanced O
structural O
aberration O
in O
one O
of O
the O
partners O
allows O
direct O
diagnostics O
for O
the O
exclusion O
or O
confirmation O
of O
genetic O
imbalance O
in O
the O
foetus O
via O
traditional O
invasive O
prenatal O
diagnostics O
. O
It O
is O
also O
possible O
to O
use O
an O
alternative O
method O
, O
Preimplantation O
Genetic O
Diagnosis O
( O
PGD O
) O
after O
in O
vitro O
fertilization O
, O
which O
prevents O
initiating O
pregnancy O
if O
genetic O
imbalance O
is O
detected O
in O
the O
embryo O
. O
Introduction O
New O
neurological O
symptoms O
in O
methylmalonic O
acidemia O
( O
MMA O
) O
patients O
after O
liver O
and/or O
kidney O
transplantation O
( O
LKT O
) O
are O
often O
described O
as O
metabolic O
stroke O
- O
like O
- O
events O
. O
Since O
calcineurin O
inhibitors O
( O
CNIs O
) O
are O
a O
well O
- O
known O
cause O
of O
new O
neurological O
symptoms O
in O
non B-LOC
- I-LOC
MMA I-LOC
transplanted O
patients O
, O
we O
investigated O
the O
incidence B-EPI
of O
CNI O
- O
induced O
neurotoxicity O
including O
posterior O
reversible O
encephalopathy O
syndrome O
( O
PRES O
) O
in O
post O
- O
transplanted O
MMA O
patients O
. O
Methods O
We O
report O
the O
two O
MMA O
patients O
treated O
with O
LKT O
in O
our O
center O
. O
Additionally O
, O
we O
performed O
a O
systematic O
review O
of O
case O
reports O
/ O
series O
of O
post O
- O
transplanted O
MMA O
patients O
and O
determined O
if O
CNI O
- O
induced O
neurotoxicity O
/ O
PRES O
was O
a O
likely O
cause O
of O
new O
neurological O
symptoms O
. O
Definite O
CNI O
- O
induced O
neurotoxicity O
was O
defined O
as O
new O
neurological O
symptoms O
during O
CNI O
treatment O
with O
symptom O
improvement O
after O
CNI O
dose O
reduction O
/ O
discontinuation O
. O
PRES O
was O
defined O
as O
CNI O
- O
induced O
neurotoxicity O
with O
signs O
of O
vasogenic O
edema O
on O
brain O
magnetic O
resonance O
imaging O
( O
MRI)-scan O
post O
- O
transplantation O
. O
Results O
Our O
two O
MMA O
patients O
both O
developed O
CNI O
- O
induced O
neurotoxicity O
, O
one O
had O
PRES O
. O
In O
literature O
, O
230 O
transplanted O
MMA O
patients O
were O
identified O
. O
Neurological O
follow O
- O
up O
was O
reported O
in O
54 O
of O
them O
, O
of O
which O
24 O
were O
excluded O
from O
analysis O
since O
no O
anti O
- O
rejection O
medication O
was O
reported O
. O
Thirty O
patients O
, O
all O
using O
CNI O
, O
were O
included O
. O
Sixteen O
patients O
( O
53 O
% O
) O
had O
no O
new O
neurological O
symptoms O
post O
- O
transplantation O
and O
five O
patients O
( O
17 O
% O
) O
had O
definite O
CNI O
neurotoxicity O
of O
whom O
two O
had O
PRES O
. O
Including O
our O
cases O
this O
results O
in O
a O
pooled B-EPI
incidence I-EPI
of O
22 O
% O
( O
7/32 O
) O
definite O
CNI O
neurotoxicity O
and O
9 O
% O
PRES O
( O
3/32 B-STAT
) O
in O
post O
- O
transplanted O
MMA O
patients O
on O
CNI O
. O
Conclusion O
In O
MMA O
post O
- O
transplanted O
patients O
with O
new O
neurological O
symptoms O
CNI O
- O
induced O
neurotoxicity O
/ O
PRES O
should O
be O
considered O
. O
Early O
recognition O
of O
CNI O
- O
induced O
neurotoxicity O
is O
essential O
to O
initiate O
dose O
reduction O
/ O
discontinuation O
of O
CNI O
to O
minimize O
persistent O
neurologic O
damage O
and O
improve O
outcome O
. O
Concise O
one O
sentence O
take O
home O
message O
In O
all O
post O
- O
transplanted O
MMA O
patients O
with O
new O
neurological O
symptoms O
CNI O
- O
induced O
neurotoxicity O
/ O
PRES O
should O
be O
considered O
, O
and O
directly O
reducing O
the O
dose O
/ O
discontinuation O
of O
CNI O
is O
essential O
. O
Introduction O
Primitive O
neuroectodermal O
tumors O
( O
PNET O
) O
form O
a O
group O
of O
tumors O
defined O
by O
their O
appearance O
that O
are O
thought O
to O
develop O
from O
primitive O
( O
undifferentiated O
) O
nerve O
cells O
in O
the O
brain O
. O
They O
are O
rare O
tumors O
and O
their O
incidence B-EPI
is O
not O
well O
defined O
. O
Case O
presentation O
An O
18 O
- O
month O
- O
old O
male O
presenting O
with O
typical O
Cushingoid O
appearance O
( O
moon O
face O
, O
central O
obesity O
, O
hirsutism O
and O
growth O
arrest O
) O
was O
admitted O
for O
evaluation O
of O
endocrine O
problems O
. O
Subsequent O
laboratory O
studies O
revealed O
markedly O
elevated O
adrenocorticotropic O
( O
ACTH O
) O
and O
cortisol O
levels O
, O
as O
well O
as O
a O
hypokalemic O
metabolic O
alkalosis O
, O
these O
data O
are O
consistent O
with O
the O
diagnosis O
of O
Cushing O
's O
disease O
. O
He O
was O
treated O
with O
metyrapone O
to O
control O
hypercortisolemia O
. O
One O
month O
and O
a O
half O
later O
, O
a O
mass O
was O
detected O
in O
the O
abdomen O
by O
ultrasonography O
. O
An O
abdominal O
Computed O
tomography O
confirmed O
a O
large O
heterogeneous O
retroperitoneal O
mass O
with O
a O
significant O
amount O
of O
extension O
into O
surrounding O
structures O
which O
was O
removed O
by O
laparoscopic O
abdominal O
surgery O
. O
The O
patient O
's O
symptoms O
completely O
resolved O
and O
the O
ACTH O
and O
cortisol O
levels O
were O
also O
greatly O
reduced O
. O
Histologically O
, O
the O
tumor O
tissue O
consistent O
with O
the O
diagnosis O
of O
the O
retroperitoneal O
primitive O
neuroectodermal O
tumor O
which O
was O
confirmed O
immunohistochemically O
. O
This O
case O
demonstrates O
the O
successful O
diagnosis O
and O
treatment O
of O
a O
rare O
neoplasm O
. O
Conclusion O
This O
is O
the O
first O
rare O
case O
with O
ectopic O
ACTH O
syndrome O
caused O
by O
the O
peripheral O
primitive O
neuroectodermal O
tumor O
. O
Non O
- O
obstructive O
azoospermia O
accounts O
for O
10 B-STAT
- O
15 O
% O
of O
male O
infertility O
, O
resulting O
in O
60 O
% O
of O
all O
cases O
of O
azoospermia O
and O
affecting O
about O
1 O
% O
of O
the O
male O
population O
. O
About O
30 O
% O
of O
these O
cases O
are O
due O
to O
Y O
chromosome O
microdeletions O
, O
chromosome O
abnormalities O
, O
or O
hormonal O
disorders O
. O
Pathogenic O
variants O
in O
genes O
on O
the O
sex O
chromosomes O
have O
key O
roles O
in O
spermatogenic O
failure O
. O
The O
co O
- O
occurrence B-EPI
of O
azoospermia O
and O
congenital O
cataracts O
ranges O
between O
1 O
in O
165,000 O
and O
1 O
in O
500,000 O
. O
Our O
28 O
- O
year O
- O
old O
patient O
with O
normal O
intelligence O
and O
abnormally O
shaped O
teeth O
presented O
with O
both O
disorders O
. O
A O
microarray O
revealed O
a O
microdeletion O
at O
Xp23.13 O
with O
a O
whole O
NHS O
gene O
deletion O
as O
well O
as O
a O
contiguous O
deletion O
of O
two O
other O
genes O
[ O
SCML1 O
and O
RAI2 O
] O
. O
This O
observation O
represents O
the O
first O
report O
of O
non O
- O
obstructive O
azoospermia O
with O
congenital O
cataracts O
and O
a O
contiguous O
deletion O
of O
the O
SCML1 O
gene O
, O
a O
transcript O
of O
which O
is O
exclusively O
expressed O
in O
the O
testis O
. O
SCML1 O
is O
the O
putative O
culprit O
gene O
, O
which O
requires O
functional O
study O
or O
animal O
experiments O
. O
Our O
analysis O
of O
60 O
known O
spermatogenesis O
failure O
- O
related O
genes O
by O
whole O
- O
exome O
sequencing O
revealed O
no O
other O
candidate O
. O
The O
Nance O
- O
Horan O
syndrome O
due O
to O
pathogenic O
variants O
in O
the O
NHS O
gene O
at O
Xp23.13 O
including O
whole O
gene O
deletion O
does O
not O
have O
azoospermia O
as O
a O
feature O
. O
Our O
report O
adds O
to O
the O
completeness O
of O
genetic O
counseling O
for O
an O
individual O
with O
azoospermia O
and O
congenital O
cataracts O
. O
Hyperthyroidism O
in O
pregnancy O
is O
associated O
with O
a O
increased O
incidence B-EPI
of O
low O
birth O
weight O
, O
preterm O
birth O
and O
admission O
to O
the O
neonatal O
intensive O
care O
unit O
. O
However O
, O
available O
treatment O
options O
are O
limited O
. O
In O
this O
report O
, O
we O
present O
a O
case O
of O
fetal O
gastroschisis O
with O
a O
history O
of O
intrauterine O
exposure O
to O
methimazole O
. O
A O
37 O
- O
year O
- O
old O
woman O
was O
diagnosed O
with O
Grave O
's O
disease O
3 O
years O
before O
her O
pregnancy O
. O
She O
had O
a O
poor O
response O
to O
propylthiouracil O
and O
required O
high O
- O
dose O
methimazole O
before O
her O
pregnancy O
. O
During O
the O
first O
trimester O
, O
she O
received O
methimazole O
120 O
mg O
/ O
day O
. O
After O
her O
12th O
week O
of O
pregnancy O
, O
she O
received O
block O
- O
and O
- O
replace O
therapy O
( O
levothyroxine O
[ O
LT4 O
] O
50 O
µg O
/ O
day O
) O
because O
of O
the O
risk O
of O
hypothyroidism O
, O
and O
the O
dose O
of O
methimazole O
was O
downtitrated O
to O
60 O
mg O
/ O
day O
. O
Fetal O
ultrasonography O
showed O
fetal O
growth O
retardation O
and O
gastroschisis O
at O
gestational O
week O
33 O
. O
The O
relationship O
between O
the O
very O
high O
doses O
of O
methimazole O
in O
the O
first O
trimester O
of O
pregnancy O
and O
the O
incidence B-EPI
of O
gastroschisis O
in O
this O
patient O
was O
not O
fully O
understood O
because O
evidence O
of O
a O
relationship O
between O
the O
use O
of O
antithyroid O
drugs O
in O
the O
first O
trimester O
and O
congenital O
abnormalities O
in O
the O
fetus O
is O
lacking O
. O
Furthermore O
block O
- O
and O
- O
replace O
therapy O
is O
not O
recommended O
in O
pregnancy O
because O
it O
requires O
a O
higher O
dose O
of O
methimazole O
. O
We O
recommend O
preconception O
counseling O
and O
early O
screening O
of O
thyroid O
function O
. O
The O
counseling O
should O
include O
the O
best O
timeline O
for O
pregnancy O
and O
a O
discussion O
of O
the O
risks O
and O
benefits O
of O
hyperthyroidism O
treatment O
options O
. O
Objective O
Health O
- O
related O
quality O
of O
life O
is O
impaired O
in O
idiopathic O
inflammatory O
myopathies O
. O
This O
study O
aimed O
to O
identify O
the O
main O
areas O
of O
the O
health O
- O
related O
quality O
of O
life O
environment O
domain O
that O
are O
affected O
in O
patients O
with O
myositis O
. O
Methods O
A O
qualitative O
study O
was O
performed O
using O
focus O
groups O
and O
applying O
the O
International O
Classification O
of O
Functioning O
, O
Disability O
, O
and O
Health O
. O
Participants O
were O
recruited O
from O
a O
cohort O
of O
323 O
adult O
inflammatory O
myopathy O
patients O
consulting O
at O
a O
reference O
center O
for O
idiopathic O
inflammatory O
myopathy O
in O
Spain B-LOC
, O
selected O
by O
the O
maximum O
variation O
strategy O
, O
and O
placed O
in O
focus O
groups O
with O
5 B-STAT
to I-STAT
7 I-STAT
patients I-STAT
per I-STAT
group I-STAT
. O
The O
number O
of O
focus O
groups O
required O
was O
determined O
by O
data O
saturation O
. O
Results O
Twenty O
- O
five O
patients O
distributed O
in O
4 O
focus O
groups O
were O
interviewed O
. O
The O
verbatim O
provided O
54 O
categories O
directly O
related O
with O
environmental O
factors O
. O
Those O
associated O
with O
products O
or O
substances O
for O
personal O
consumption O
( O
e110 O
) O
, O
health O
professionals O
( O
e355 O
) O
, O
health O
services O
, O
systems O
and O
policies O
( O
e580 O
) O
, O
products O
and O
technology O
for O
personal O
use O
in O
daily O
living O
( O
e115 O
) O
, O
and O
immediate O
family O
( O
e310 O
) O
were O
the O
ones O
most O
frequently O
reported O
. O
Conclusion O
The O
results O
of O
this O
study O
led O
to O
identification O
of O
several O
environmental O
factors O
that O
affect O
the O
health O
- O
related O
quality O
of O
life O
of O
patients O
with O
myositis O
. O
Remedial O
interventions O
should O
be O
designed O
to O
address O
some O
of O
these O
factors O
. O
Objective O
In O
observational O
data O
, O
lower O
levels O
of O
lipoprotein(a O
) O
have O
been O
associated O
with O
greater O
prevalence B-EPI
of O
type O
2 O
diabetes O
. O
Whether O
pharmacologic O
lowering O
of O
lipoprotein(a O
) O
influences O
incident O
type O
2 O
diabetes O
is O
unknown O
. O
We O
determined O
the O
relationship O
of O
lipoprotein(a O
) O
concentration O
with O
incident O
type O
2 O
diabetes O
and O
effects O
of O
treatment O
with O
alirocumab O
, O
a O
PCSK9 O
inhibitor O
. O
Research O
design O
and O
methods O
In O
the O
ODYSSEY O
OUTCOMES O
trial O
alirocumab O
was O
compared O
with O
placebo O
in O
patients O
with O
acute O
coronary O
syndrome O
. O
Incident O
diabetes O
was O
determined O
from O
laboratory O
, O
medication O
, O
and O
adverse O
event O
data O
. O
Results O
Among O
13,480 O
patients O
without O
diabetes O
at O
baseline O
, O
1,324 O
developed O
type O
2 O
diabetes O
over O
a O
median O
2.7 O
years O
. O
Median O
baseline O
lipoprotein(a O
) O
was O
21.9 O
mg O
/ O
dL. O
With O
placebo O
, O
10 O
mg O
/ O
dL O
lower O
baseline O
lipoprotein(a O
) O
was O
associated O
with O
hazard O
ratio O
1.04 O
( O
95 O
% O
CI O
1.02 O
- O
1.06 O
, O
P O
< O
0.001 O
) O
for O
incident O
type O
2 O
diabetes O
. O
Alirocumab O
reduced O
lipoprotein(a O
) O
by O
a O
median O
23.2 O
% O
with O
greater O
absolute O
reductions O
from O
higher O
baseline O
levels O
and O
no O
overall O
effect O
on O
incident O
type O
2 O
diabetes O
( O
hazard O
ratio O
0.95 O
, O
95 O
% O
CI O
0.85 O
- O
1.05 O
) O
. O
At O
low O
baseline O
lipoprotein(a O
) O
levels O
, O
alirocumab O
tended O
to O
reduce O
incident O
type O
2 O
diabetes O
, O
while O
at O
high O
baseline O
lipoprotein(a O
) O
alirocumab O
tended O
to O
increase O
incident O
type O
2 O
diabetes O
compared O
with O
placebo O
( O
treatment O
- O
baseline O
lipoprotein(a O
) O
interaction O
P O
= O
0.006 O
) O
. O
In O
the O
alirocumab O
group O
, O
a O
10 O
mg O
/ O
dL O
decrease O
in O
lipoprotein(a O
) O
from O
baseline O
was O
associated O
with O
hazard O
ratio O
1.07 O
( O
95 O
% O
CI O
1.03 O
- O
1.12 O
; O
P O
= O
0.0002 O
) O
for O
incident O
type O
2 O
diabetes O
. O
Conclusions O
In O
patients O
with O
acute O
coronary O
syndrome O
, O
baseline O
lipoprotein(a O
) O
concentration O
associated O
inversely O
with O
incident O
type O
2 O
diabetes O
. O
Alirocumab O
had O
neutral O
overall O
effect O
on O
incident O
type O
2 O
diabetes O
. O
However O
, O
treatment O
- O
related O
reductions O
in O
lipoprotein(a O
) O
, O
more O
pronounced O
from O
high O
baseline O
levels O
, O
were O
associated O
with O
increased O
risk O
of O
incident O
type O
2 O
diabetes O
. O
Whether O
these O
findings O
pertain O
to O
other O
therapies O
that O
reduce O
lipoprotein(a O
) O
is O
undetermined O
. O
Pneumocystis O
jirovecii O
pneumonia O
( O
PJP O
) O
is O
an O
opportunistic O
infectious O
disease O
well O
described O
in O
patients O
living O
with O
HIV O
( O
PLHIV O
) O
but O
that O
can O
occur O
in O
other O
immunosuppressed O
patients O
. O
Currently O
, O
its O
incidence B-EPI
decreases O
in O
PLHIV O
but O
increases O
in O
non O
- O
HIV O
immunosuppressed O
patients O
, O
particularly O
in O
case O
of O
hematological O
diseases O
. O
Thus O
, O
in O
elderly O
, O
the O
diagnosis O
of O
PJP O
should O
be O
evoked O
in O
case O
of O
subacute O
pneumonia O
rapidly O
evolving O
to O
an O
acute O
respiratory O
distress O
, O
with O
or O
without O
interstitial O
pneumonia O
at O
chest O
radiography O
, O
and O
a O
context O
of O
immunosuppression O
. O
Introduction O
Patients O
with O
Noonan O
and O
Williams O
- O
Beuren O
syndrome O
present O
similar O
facial O
phenotypes O
modulated O
by O
their O
ethnic O
background O
. O
Although O
distinctive O
facial O
features O
have O
been O
reported O
, O
studies O
show O
a O
variable O
incidence B-EPI
of O
those O
characteristics O
in O
populations O
with O
diverse O
ancestry O
. O
Hence O
, O
a O
differential O
diagnosis O
based O
on O
reported O
facial O
features O
can O
be O
challenging O
. O
Although O
accurate O
diagnoses O
are O
possible O
with O
genetic O
testing O
, O
they O
are O
not O
available O
in O
developing O
and O
remote O
regions O
. O
Methods O
We O
used O
a O
facial O
analysis O
technology O
to O
identify O
the O
most O
discriminative O
facial O
metrics O
between O
286 O
patients O
with O
Noonan O
and O
161 O
with O
Williams O
- O
Beuren O
syndrome O
with O
diverse O
ethnic O
background O
. O
We O
quantified O
the O
most O
discriminative O
metrics O
, O
and O
their O
ranges O
both O
globally O
and O
in O
different O
ethnic O
groups O
. O
We O
also O
created O
population O
- O
based O
appearance O
images O
that O
are O
useful O
not O
only O
as O
clinical O
references O
but O
also O
for O
training O
purposes O
. O
Finally O
, O
we O
trained O
both O
global O
and O
ethnic O
- O
specific O
machine O
learning O
models O
with O
previous O
metrics O
to O
distinguish O
between O
patients O
with O
Noonan O
and O
Williams O
- O
Beuren O
syndromes O
. O
Results O
We O
obtained O
a O
classification O
accuracy O
of O
85.68 O
% O
in O
the O
global O
population O
evaluated O
using O
cross O
- O
validation O
, O
which O
improved B-STAT
to O
90.38 O
% O
when O
we O
adapted O
the O
facial O
metrics O
to O
the O
ethnicity O
of O
the O
patients O
( O
p O
= O
0.024 O
) O
. O
Conclusion O
Our O
facial O
analysis O
provided O
for O
the O
first O
time O
quantitative O
reference O
facial O
metrics O
for O
the O
differential O
diagnosis O
Noonan O
and O
Williams O
- O
Beuren O
syndromes O
in O
diverse O
populations O
. O
Testicular O
cancer O
is O
the O
most O
common O
malignant O
tumor O
in O
young O
men O
, O
and O
its O
incidence B-EPI
has O
increased O
in O
recent O
years O
. O
The O
tumor O
microenvironment O
( O
TME O
) O
plays O
a O
crucial O
role O
in O
the O
development O
and O
progression O
of O
tumors O
; O
however O
, O
the O
TME O
of O
testicular O
germ O
cell O
tumor O
( O
TGCT O
) O
is O
poorly O
understood O
. O
In O
this O
study O
, O
we O
downloaded O
information O
for O
156 O
TGCT O
cases O
from O
The O
Cancer O
Genome O
Atlas O
( O
TCGA O
) O
database O
, O
used O
the O
ESTIMATE O
method O
to O
determine O
immune O
and O
stromal O
scores O
, O
and O
used O
CIBERSORT O
to O
calculate O
the O
proportion O
of O
tumor O
- O
infiltrating O
immune O
cells O
( O
TICs O
) O
. O
The O
differentially O
expressed O
genes O
were O
subjected O
to O
a O
COX O
regression O
analysis O
and O
used O
for O
the O
construction O
of O
a O
protein O
- O
protein O
interaction O
( O
PPI O
) O
network O
. O
Toll O
- O
like O
receptor O
2 O
( O
TLR2 O
) O
was O
identified O
as O
a O
predictive O
marker O
by O
combining O
the O
results O
of O
the O
Cox O
regression O
analysis O
and O
PPI O
network O
. O
A O
survival O
analysis O
showed O
that O
TLR2 O
was O
positively O
correlated O
with O
TGCT O
survival O
. O
A O
gene O
set O
enrichment O
analysis O
indicated O
that O
genes O
in O
the O
high O
TLR2 O
expression O
group O
were O
enriched O
for O
cell O
adhesion O
molecules O
( O
CAMs O
) O
and O
the O
chemokine O
signaling O
pathway O
, O
and O
genes O
in O
the O
low O
TLR2 O
expression O
group O
were O
mainly O
enriched O
in O
the O
spliceosome O
. O
Regarding O
proportions O
of O
TICs O
, O
naive O
B O
cells O
and O
follicular O
helper O
T O
cells O
were O
negatively O
correlated O
with O
the O
expression O
of O
TLR2 O
. O
This O
suggests O
that O
as O
TLR2 O
expression O
increases O
, O
the O
immunocompetence O
of O
the O
TME O
decreases O
. O
The O
expression O
of O
TLR2 O
may O
affect O
the O
prognosis O
of O
TGCT O
, O
suggesting O
that O
this O
locus O
can O
be O
used O
as O
a O
prognostic O
factor O
for O
TGCT O
. O
The O
clinical O
presentation O
of O
optic O
neuritis O
is O
quite O
characteristic O
, O
and O
the O
epidemiology O
, O
differential O
diagnosis O
, O
and O
treatment O
protocol O
are O
well O
established O
. O
However O
, O
when O
the O
presentation O
of O
optic O
neuritis O
is O
atypical O
, O
bilateral O
, O
and O
intravenous O
steroid O
- O
resistant O
, O
the O
treatment O
guidelines O
are O
quite O
nebulous O
. O
We O
present O
a O
case O
of O
bilateral O
severe O
double O
- O
seronegative O
optic O
neuritis O
with O
catastrophic O
vision O
loss O
and O
intravenous O
steroid O
resistance O
. O
After O
an O
exhaustive O
investigation O
, O
we O
empirically O
treated O
our O
patient O
with O
plasma O
exchange O
therapy O
and O
obtained O
a O
dramatic O
recovery O
of O
vision O
. O
When O
an O
immune O
etiology O
is O
suspected O
, O
this O
case O
is O
instructive O
vis O
- O
a O
- O
vis O
the O
utility O
of O
plasma O
exchange O
in O
refractory O
cases O
of O
optic O
neuritis O
despite O
seronegativity O
. O
Despite O
the O
known O
association O
of O
cardiac O
rupture O
with O
acute O
myocardial O
infarction O
( O
AMI O
) O
, O
it O
is O
still O
unclear O
whether O
the O
clinical O
characteristics O
are O
associated O
with O
the O
risk O
of O
in O
- O
hospital O
mortality O
in O
patients O
with O
AMI O
complicated O
by O
cardiac O
rupture O
. O
The O
purpose O
of O
this O
study O
was O
to O
investigate O
the O
association O
between O
the O
time O
of O
cardiac O
rupture O
occurrence B-EPI
and O
the O
risk O
of O
in O
- O
hospital O
mortality O
after O
AMI O
. O
We O
conducted O
a O
retrospective O
analysis O
of O
multicenter O
registry O
data O
from O
eight O
medical O
universities O
in O
Eastern B-LOC
Japan I-LOC
. O
From O
10,278 O
consecutive O
patients O
with O
AMI O
, O
we O
included O
183 O
patients O
who O
had O
cardiac O
rupture O
after O
AMI O
, O
and O
examined O
the O
incidence B-EPI
of O
in O
- O
hospital O
deaths O
during O
a O
median O
follow O
- O
up O
of O
26 O
days O
. O
Patients O
were O
stratified O
into O
three O
groups O
according O
to O
the O
AMI O
- O
to O
- O
cardiac O
rupture O
time O
, O
namely O
the O
> O
24 O
- O
h O
group O
( O
n O
= O
111 O
) O
, O
24 O
- O
48 O
- O
h O
group O
( O
n O
= O
20 O
) O
, O
and O
< O
48 O
- O
h O
group O
( O
n O
= O
52 O
) O
. O
Cox O
proportional O
hazards O
regression O
analysis O
was O
used O
to O
estimate O
the O
hazard O
ratio O
( O
HR O
) O
and O
the O
confidence O
interval O
( O
CI O
) O
for O
in O
- O
hospital O
mortality O
. O
Around O
87 B-STAT
( O
48 O
% O
) O
patients O
experienced O
in O
- O
hospital O
death O
and O
126 B-STAT
( O
67 O
% O
) O
underwent O
a O
cardiac O
surgery O
. O
Multivariable O
Cox O
regression O
analysis O
revealed O
a O
non O
- O
linear O
association O
across O
the O
three O
groups O
for O
mortality O
( O
HR O
[ O
CI O
] O
; O
< O
24 O
h O
: O
1.0 O
, O
reference O
; O
24 O
- O
48 O
h O
: O
0.73 O
[ O
0.27 O
- O
1.86 O
] O
; O
> O
48 O
h O
: O
2.25 O
[ O
1.22 O
- O
4.15 O
] O
) O
after O
adjustments O
for O
age O
, O
sex O
, O
Killip O
classification O
, O
percutaneous O
coronary O
intervention O
, O
blood O
pressure O
, O
creatinine O
, O
peak O
creatine O
kinase O
myocardial O
band O
fraction O
, O
left O
ventricular O
ejection O
fraction O
, O
and O
type O
of O
rupture O
. O
Cardiac O
surgery O
was O
independently O
associated O
with O
a O
reduction O
in O
the O
HR O
of O
mortality O
( O
HR O
[ O
CI O
] O
: O
0.27 O
[ O
0.12 O
- O
0.61 O
] O
) O
and O
attenuated O
the O
association O
between O
the O
three O
AMI O
- O
to O
- O
cardiac O
rupture O
time O
categories O
and O
mortality O
( O
statistically O
non O
- O
significant O
) O
in O
the O
Cox O
model O
. O
These O
data O
suggest O
that O
the O
AMI O
- O
to O
- O
cardiac O
rupture O
time O
contributes O
significantly O
to O
the O
risk O
of O
in O
- O
hospital O
mortality O
; O
however O
, O
rapid O
diagnosis O
and O
prompt O
surgical O
interventions O
are O
crucial O
for O
improving O
outcomes O
in O
patients O
with O
cardiac O
rupture O
after O
AMI O
. O
The O
inherited O
bone O
marrow O
failure O
syndromes O
( O
IBMFS O
) O
are O
a O
rare O
yet O
clinically O
important O
cause O
of O
neonatal O
hematological O
and O
non O
- O
hematological O
manifestations O
. O
Many O
of O
these O
syndromes O
, O
such O
as O
Fanconi O
anemia O
, O
dyskeratosis O
congenita O
and O
Diamond O
- O
Blackfan O
anemia O
, O
confer O
risks O
of O
multiple O
medical O
complications O
later O
in O
life O
, O
including O
an O
increased O
risk O
of O
cancer O
. O
Some O
IBMFS O
may O
present O
with O
cytopenias O
in O
the O
neonatal O
period O
whereas O
others O
may O
present O
only O
with O
congenital O
physical O
abnormalities O
and O
progress O
to O
pancytopenia O
later O
in O
life O
. O
A O
thorough O
family O
history O
and O
detailed O
physical O
examination O
are O
integral O
to O
the O
work O
- O
up O
of O
any O
neonate O
in O
whom O
there O
is O
a O
high O
index O
of O
suspicion O
for O
an O
IBMFS O
. O
Correct O
detection O
and O
diagnosis O
of O
these O
disorders O
is O
important O
for O
appropriate O
long O
- O
term O
medical O
surveillance O
and O
counseling O
not O
only O
for O
the O
patient O
but O
also O
for O
appropriate O
genetic O
counselling O
of O
their O
families O
regarding O
recurrence O
risks O
in O
future O
children O
and O
generations O
. O
Background O
May O
- O
Hegglin O
anomaly O
is O
an O
autosomal O
dominant O
inherited O
condition O
, O
characterized O
by O
thrombocytopenia O
, O
giant O
platelets O
and O
Dohle O
- O
like O
bodies O
. O
Incidence B-EPI
is O
unknown O
and O
affected O
individuals O
can O
show O
from O
mild O
to O
moderate O
- O
severe O
haemorrhagic O
symptoms O
. O
The O
cyst O
of O
cavum O
veli O
interpositi O
( O
a O
virtual O
space O
filled O
with O
fluid O
within O
the O
third O
ventricle O
) O
is O
rarely O
reported O
in O
the O
foetal O
period O
. O
Furthermore O
, O
it O
is O
unclear O
whether O
isolated O
cavum O
veli O
interpositi O
cysts O
are O
a O
normal O
variant O
or O
developmental O
malformations O
. O
The O
simultaneous O
presence O
of O
these O
two O
anomalies O
was O
never O
described O
. O
Case O
presentation O
We O
describe O
a O
very O
rare O
case O
of O
a O
twin O
monochorionic O
pregnancy O
in O
a O
woman O
with O
the O
May O
- O
Hegglin O
anomaly O
, O
whose O
foetuses O
carried O
cavum O
veli O
interpositi O
cysts O
. O
Since O
childhood O
, O
our O
patient O
had O
shown O
macro O
- O
thrombocytopenia O
, O
deafness O
and O
bleeding O
( O
epistaxis O
and O
menorrhagia O
) O
, O
but O
she O
was O
misdiagnosed O
until O
the O
age O
of O
30 O
years O
when O
our O
Centre O
identified O
a O
de O
novo O
allelic O
variant O
in O
the O
gene O
MYH9 O
coding O
for O
the O
non O
- O
muscle O
myosin O
heavy O
chain O
IIa O
. O
Our O
patient O
bled O
neither O
during O
the O
pregnancy O
, O
nor O
in O
the O
peripartum O
period O
. O
Children O
are O
now O
eight O
- O
months O
- O
old O
and O
have O
never O
bled O
, O
although O
both O
inherited O
the O
MYH9 O
variant O
and O
have O
thrombocytopenia O
with O
giant O
platelets O
. O
Furthermore O
, O
none O
of O
them O
developed O
psychomotor O
disorders O
. O
Conclusions O
To O
the O
best O
of O
our O
knowledge O
, O
this O
is O
the O
sixth O
case O
of O
twin O
pregnancy O
in O
a O
woman O
carrying O
May O
- O
Hegglin O
anomaly O
and O
the O
first O
one O
with O
cavum O
veli O
interpositi O
cysts O
in O
the O
neonates O
. O
We O
speculate O
that O
MYH9 O
could O
have O
, O
at O
least O
in O
part O
, O
played O
a O
role O
in O
the O
development O
of O
both O
conditions O
, O
as O
this O
gene O
has O
a O
pleiotropic O
effect O
. O
Smith O
- O
Magenis O
syndrome O
( O
SMS O
) O
, O
characterized O
by O
dysmorphic O
features O
, O
neurodevelopmental O
disorder O
, O
and O
sleep O
disturbance O
, O
is O
due O
to O
an O
interstitial O
deletion O
of O
chromosome O
17p11.2 O
( O
90 O
% O
) O
or O
to O
point O
mutations O
in O
the O
RAI1 O
gene O
. O
In O
this O
retrospective O
cohort O
, O
we O
studied O
the O
clinical O
, O
cognitive O
, O
and O
behavioral O
profile O
of O
47 O
European O
patients O
with O
SMS O
caused O
by O
a O
17p11.2 O
deletion O
. O
We O
update O
the O
clinical O
and O
neurobehavioral O
profile O
of O
SMS O
. O
Intrauterine O
growth O
was O
normal O
in O
most O
patients O
. O
Prenatal O
anomalies O
were O
reported O
in O
15 B-STAT
% I-STAT
. O
60 B-STAT
% I-STAT
of O
our O
patients O
older O
than O
10 O
years O
were O
overweight O
. O
Prevalence B-EPI
of O
heart O
defects O
( O
6.5 O
% O
tetralogy O
of O
Fallot B-LOC
, O
6.5 O
% O
pulmonary O
stenosis O
) O
, O
ophthalmological O
problems O
( O
89 O
% O
) O
, O
scoliosis O
( O
43 O
% O
) O
, O
or O
deafness O
( O
32 O
% O
) O
were O
consistent O
with O
previous O
reports O
. O
Epilepsy O
was O
uncommon O
( O
2 O
% O
) O
. O
We O
identified O
a O
high O
prevalence B-EPI
of O
obstipation O
( O
45 O
% O
) O
. O
All O
patients O
had O
learning O
difficulties O
and O
developmental O
delay O
, O
but O
ID O
range O
was O
wide O
and O
10 O
% O
of O
patients O
had O
IQ O
in O
the O
normal O
range O
. O
Behavioral O
problems O
included O
temper O
tantrums O
and O
other O
difficult O
behaviors O
( O
84 O
% O
) O
and O
night O
- O
time O
awakenings O
( O
86 O
% O
) O
. O
Optimal O
care O
of O
SMS O
children O
is O
multidisciplinary O
and O
requires O
important O
parental O
involvement O
. O
In O
our O
series O
, O
half O
of O
patients O
were O
able O
to O
follow O
adapted O
schooling O
, O
but O
70 O
% O
of O
parents O
had O
to O
adapt O
their O
working O
time O
, O
illustrating O
the O
medical O
, O
social O
, O
educative O
, O
and O
familial O
impact O
of O
having O
a O
child O
with O
SMS O
. O
Context O
: O
There O
has O
been O
concern O
that O
GH O
treatment O
of O
children O
might O
increase O
meningioma O
risk O
. O
Results O
of O
published O
studies O
have O
been O
inconsistent O
and O
limited O
. O
Objective O
: O
To O
examine O
meningioma O
risks O
in O
relation O
to O
GH O
treatment O
. O
Design O
: O
Cohort O
study O
with O
follow O
- O
up O
via O
cancer O
registries O
and O
other O
registers O
. O
Setting O
: O
Population O
- O
based O
. O
Patients O
: O
A O
cohort O
of O
10,403 O
patients O
treated O
in O
childhood O
with O
recombinant O
GH O
in O
five O
European O
countries O
since O
this O
treatment O
was O
first O
used O
in O
1984 O
. O
Expected O
rates O
from O
national O
cancer O
registration O
statistics O
. O
Main O
Outcome O
Measures O
: O
Risk O
of O
meningioma O
incidence B-EPI
. O
Results O
: O
During O
follow O
- O
up O
, O
38 O
meningiomas O
occurred O
. O
Meningioma O
risk O
was O
greatly O
raised O
in O
the O
cohort O
overall O
[ O
standardized O
incidence B-EPI
ratio O
( O
SIR O
) O
= O
75.4 O
; O
95 O
% O
CI O
: O
54.9 O
to O
103.6 O
] O
, O
as O
a O
consequence O
of O
high O
risk O
in O
subjects O
who O
had O
received O
radiotherapy O
for O
underlying O
malignancy O
( O
SIR O
= O
658.4 O
; O
95 O
% O
CI O
: O
460.4 O
to O
941.7 O
) O
. O
Risk O
was O
not O
significantly O
raised O
in O
patients O
who O
did O
not O
receive O
radiotherapy O
. O
Risk O
in O
radiotherapy O
- O
treated O
patients O
was O
not O
significantly O
related O
to O
mean O
daily O
dose O
of O
GH O
, O
duration O
of O
GH O
treatment O
, O
or O
cumulative O
dose O
of O
GH O
. O
Conclusions O
: O
Our O
data O
add O
to O
evidence O
of O
very O
high O
risk O
of O
meningioma O
in O
patients O
treated O
in O
childhood O
with O
GH O
after O
cranial O
radiotherapy O
, O
but O
suggest O
that O
GH O
may O
not O
affect O
radiotherapy O
- O
related O
risk O
, O
and O
that O
there O
is O
no O
material O
raised O
risk O
of O
meningioma O
in O
GH O
- O
treated O
patients O
who O
did O
not O
receive O
radiotherapy O
. O
Aims O
Takotsubo O
syndrome O
( O
TTS O
) O
is O
a O
form O
of O
acute O
myocardial O
inflammation O
, O
often O
triggered O
by O
catecholamine O
release O
surges O
, O
which O
accounts O
for O
approximately O
10 O
% O
of O
' O
myocardial O
infarctions O
' O
in O
female O
patients O
above O
the O
age O
of O
50 O
. O
Its O
associated O
substantial O
risk O
of O
in O
- O
hospital O
mortality O
is O
mainly O
driven O
by O
the O
development O
of O
hypotension O
and O
shock O
. O
While O
hypotension O
is O
induced O
largely O
by O
factors O
other O
than O
low O
cardiac O
output O
, O
its O
precise O
cause O
is O
unknown O
, O
and O
clinical O
parameters O
associated O
with O
hypotension O
have O
not O
been O
identified O
previously O
. O
We O
therefore O
sought O
to O
identify O
the O
incidence B-EPI
and O
clinical O
/ O
laboratory O
correlates O
of O
early O
hypotension O
in O
TTS O
. O
Methods O
and O
results O
We O
analysed O
the O
in O
- O
hospital O
data O
of O
patients O
recruited O
to O
the B-LOC
South I-LOC
Australian I-LOC
TTS I-LOC
Registry I-LOC
. O
Associations O
between O
the O
development O
of O
hypotension O
, O
patient O
demographics O
, O
severity O
of O
the O
acute O
TTS O
attack O
, O
and O
key O
biochemical O
markers O
were O
sought O
. O
One O
hundred O
thirteen O
out O
of O
319 O
patients O
( O
35 O
% O
) O
were O
hypotensive O
( O
median O
systolic O
blood O
pressure O
80 O
mmHg O
) O
during O
their O
index O
hospitalization O
. O
Development O
of O
hypotension O
preceded O
all O
in O
- O
hospital O
deaths O
( O
n O
= O
8) O
. O
On O
univariate O
analyses O
, O
patients O
who O
developed O
hypotension O
had O
lower O
left O
ventricular O
ejection O
fraction O
( O
P O
= O
0.009 O
) O
, O
and O
higher O
plasma O
N O
- O
terminal O
pro O
brain O
natriuretic O
peptide O
and O
troponin O
- O
T O
concentrations O
( O
P O
= O
0.046 O
and O
0.008 O
, O
respectively O
) O
, O
all O
markers O
of O
severity O
of O
the O
TTS O
attack O
; O
hypotension O
also O
occurred O
less O
commonly O
in O
male O
than O
in O
female O
patients O
( O
P O
= O
0.014 O
) O
. O
On O
multivariate O
linear O
regression O
analysis O
, O
female O
sex O
and O
lower O
left O
ventricular O
ejection O
fraction O
were O
independent O
correlates O
of O
the O
development O
of O
hypotension O
( O
P O
= O
0.009 O
and O
0.010 O
, O
respectively O
) O
. O
Conclusions O
Early O
development O
of O
hypotension O
is O
very O
common O
in O
TTS O
, O
and O
its O
presence O
is O
associated O
with O
a O
substantial O
risk O
of O
in O
- O
hospital O
mortality O
. O
Hypotension O
is O
a O
marker O
of O
severe O
TTS O
attacks O
and O
occurs B-EPI
more O
commonly O
in O
female O
TTS O
patients O
. O
Background O
Using O
data O
from O
the O
GARFIELD O
- O
AF O
( O
Global O
Anticoagulant O
Registry O
in O
the O
FIELD O
-Atrial O
Fibrillation O
) O
, O
we O
evaluated O
the O
impact O
of O
chronic O
kidney O
disease O
( O
CKD O
) O
stage O
on O
clinical O
outcomes O
in O
patients O
with O
newly O
diagnosed O
atrial O
fibrillation O
( O
AF O
) O
. O
Methods O
and O
Results O
GARFIELD O
- O
AF O
is O
a O
prospective O
registry O
of O
patients O
from O
35 O
countries O
, O
including O
patients O
from O
Asia B-LOC
( O
China B-LOC
, O
India B-LOC
, O
Japan B-LOC
, O
Singapore B-LOC
, O
South B-LOC
Korea I-LOC
, O
and O
Thailand B-LOC
) O
. O
Consecutive O
patients O
enrolled O
( O
2013 O
- O
2016 O
) O
were O
classified O
with O
no O
, O
mild O
, O
or O
moderate O
- O
to O
- O
severe O
CKD O
, O
based O
on O
the O
National O
Kidney O
Foundation O
's O
Kidney O
Disease O
Outcomes O
Quality O
Initiative O
guidelines O
. O
Data O
on O
CKD O
status O
and O
outcomes O
were O
available O
for O
33 O
024 O
of O
34 O
854 O
patients O
( O
including O
9491 O
patients O
from O
Asia B-LOC
) O
; O
10.9 O
% O
( O
n=3613 O
) O
had O
moderate O
- O
to O
- O
severe O
CKD O
, O
16.9 O
% O
( O
n=5595 O
) O
mild O
CKD O
, O
and O
72.1 O
% O
( O
n=23 O
816 O
) O
no O
CKD O
. O
The O
use O
of O
oral O
anticoagulants O
was O
influenced O
by O
stroke O
risk O
( O
ie O
, O
post O
hoc O
assessment O
of O
CHA O
2 O
DS O
2 O
- O
VAS O
c O
score O
) O
, O
but O
not O
by O
CKD O
stage O
. O
The O
quality O
of O
anticoagulant O
control O
with O
vitamin O
K O
antagonists O
did O
not O
differ O
with O
CKD O
stage O
. O
After O
adjusting O
for O
baseline O
characteristics O
and O
antithrombotic O
use O
, O
both O
mild O
and O
moderate O
- O
to O
- O
severe O
CKD O
were O
independent O
risk O
factors O
for O
all O
- O
cause O
mortality O
. O
Moderate O
- O
to O
- O
severe O
CKD O
was O
independently O
associated O
with O
a O
higher O
risk O
of O
stroke O
/ O
systemic O
embolism O
, O
major O
bleeding O
, O
new O
- O
onset O
acute O
coronary O
syndrome O
, O
and O
new O
or O
worsening O
heart O
failure O
. O
The O
impact O
of O
moderate O
- O
to O
- O
severe O
CKD O
on O
mortality O
was O
significantly O
greater O
in O
patients O
from O
Asia B-LOC
than O
the O
rest O
of O
the O
world O
( O
P=0.001 O
) O
. O
Conclusions O
In O
GARFIELD O
- O
AF O
, O
moderate O
- O
to O
- O
severe O
CKD O
was O
independently O
associated O
with O
stroke O
/ O
systemic O
embolism O
, O
major O
bleeding O
, O
and O
mortality O
. O
The O
effect O
of O
moderate O
- O
to O
- O
severe O
CKD O
on O
mortality O
was O
even O
greater O
in O
patients O
from O
Asia B-LOC
than O
the O
rest O
of O
the O
world O
. O
Clinical O
Trial O
Registration O
URL O
: O
http://www.clinicaltrials.gov O
. O
Unique O
identifier O
: O
NCT O
01090362 O
. O
The O
high O
incidence B-EPI
of O
surgically O
induced O
heart O
block O
in O
patients O
with O
levotransposition O
of O
the O
great O
arteries O
is O
now O
better O
understood O
because O
of O
recent O
anatomic O
demonstration O
of O
an O
unusual O
anterior O
location O
of O
the O
atrioventricular O
specialized O
conducting O
tissue O
. O
The O
two O
cases O
reported O
herein O
proved O
electrophysiologic O
confirmation O
of O
this O
previously O
described O
anatomy O
. O
The O
specialized O
conducting O
bundle O
was O
easily O
and O
consistently O
identified O
and O
then O
avoided O
in O
successful O
surgical O
correction O
in O
one O
patient O
with O
common O
ventricle O
, O
type O
A-3 O
, O
and O
in O
another O
with O
corrected O
transposition O
, O
large O
ventricular O
septal O
defect O
, O
and O
valvular O
pulmonary O
stenosis O
. O
Electrophysiologic O
identification O
of O
the O
atrioventricular O
conduction O
tissue O
at O
the O
time O
of O
operation O
may O
decrease O
the O
incidence O
of O
heart O
block O
and O
offers O
additional O
optimism O
for O
successful O
correction O
of O
levotransposition O
complexes O
. O
Objective O
Intellectual O
Disability O
( O
ID O
) O
represents O
a O
neuropsychiatric O
disorder O
, O
which O
its O
etiopathogenesis O
remains O
insufficiently O
understood O
. O
Mutations O
in O
the O
Aristaless O
Related O
Homeobox O
gene O
( O
ARX O
) O
have O
been O
identified O
to O
cause O
syndromic O
and O
nonsyndromic O
( O
NS O
- O
ID O
) O
. O
The O
most O
recurrent O
mutation O
of O
this O
gene O
is O
a O
duplication O
of O
24pb O
, O
c.428 O
- O
451dup O
. O
Epidemiological O
and O
genetic O
studies O
about O
ID O
in O
the O
Moroccan O
population O
remain O
very O
scarce O
, O
and O
none O
study O
is O
carried O
out O
on O
the O
ARX O
gene O
. O
This O
work O
aimed O
to O
study O
c.428 O
- O
451dup O
( O
24 O
bp O
) O
mutation O
in O
the O
exon O
2 O
of O
the O
ARX O
gene O
in O
118 O
males O
' O
Moroccan O
patients O
with O
milder O
NS O
- O
ID O
to O
evaluate O
if O
the O
gene O
screening O
is O
a O
good O
tool O
for O
identifying O
NS O
- O
ID O
. O
Results O
Our O
mutational O
analysis O
did O
not O
show O
any O
dup(24pb O
) O
in O
our O
patients O
. O
This O
is O
because O
based O
on O
findings O
from O
previous O
studies O
that O
found O
ARX O
mutations O
in O
70 O
% O
of O
families O
with O
NS O
- O
ID O
, O
and O
in O
most O
cases O
, O
1.5 B-STAT
- O
6.1 O
% O
of O
individuals O
with O
NS O
- O
ID O
have O
this O
duplication O
. O
Since O
1/118 B-STAT
= O
0.0084 O
( O
0.84 B-STAT
% I-STAT
) O
is O
not O
much O
different O
from O
1.5 O
% O
, O
then O
it O
is O
reasonable O
that O
this O
could O
a O
sample O
size O
artifact O
. O
A O
complete O
screening O
of O
the O
entire O
ARX O
gene O
, O
including O
the O
five O
exons O
, O
should O
be O
fulfilled O
. O
Further O
investigations O
are O
required O
to O
confirm O
these O
results O
. O
Snakebites O
in O
Europe B-LOC
are O
mostly O
due O
to O
bites O
from O
Viperidae O
species O
of O
the O
genus O
Vipera O
. O
This O
represents O
a O
neglected O
public O
health O
hazard O
with O
poorly O
defined O
incidence B-EPI
, O
morbidity O
and O
mortality O
. O
In O
Europe B-LOC
, O
fourteen O
species O
of O
O
true O
vipers O
O
( O
subfamily O
Viperinae O
) O
are O
present O
, O
eleven O
of O
which O
belong O
to O
the O
genus O
Vipera O
. O
Amongst O
these O
, O
the O
main O
medically O
relevant O
species O
due O
to O
their O
greater O
diffusion O
across O
Europe B-LOC
and O
the O
highest O
number O
of O
registered O
snakebites O
are O
six O
, O
namely O
: O
Vipera O
ammodytes O
, O
V. O
aspis O
, O
V. O
berus O
, O
V. O
latastei O
, O
V. O
seoanei O
and O
V. O
ursinii O
. O
Generally O
speaking O
, O
viper O
venom O
composition O
is O
characterised O
by O
many O
different O
toxin O
families O
, O
like O
phospholipases O
A2 O
, O
snake O
venom O
serine O
proteases O
, O
snake O
venom O
metalloproteases O
, O
cysteine O
- O
rich O
secretory O
proteins O
, O
C O
- O
type O
lectins O
, O
disintegrins O
, O
haemorrhagic O
factors O
and O
coagulation O
inhibitors O
. O
A O
suspected O
snakebite O
is O
often O
associated O
with O
severe O
pain O
, O
erythema O
, O
oedema O
and O
, O
subsequently O
, O
the O
onset O
of O
an O
ecchymotic O
area O
around O
one O
or O
two O
visible O
fang O
marks O
. O
In O
the O
field O
, O
the O
affected O
limb O
should O
be O
immobilised O
and O
mildly O
compressed O
with O
a O
bandage O
, O
which O
can O
then O
be O
removed O
once O
the O
patient O
is O
being O
treated O
in O
hospital O
. O
The O
clinician O
should O
advise O
the O
patient O
to O
remain O
calm O
to O
reduce O
blood O
circulation O
and O
, O
therefore O
, O
decrease O
the O
spread O
of O
the O
toxins O
. O
In O
the O
case O
of O
pain O
, O
an O
analgesic O
therapy O
can O
be O
administered O
, O
the O
affected O
area O
can O
be O
treated O
with O
hydrogen O
peroxide O
or O
clean O
water O
. O
However O
, O
anti O
- O
inflammatory O
drugs O
and O
disinfection O
with O
alcohol O
or O
alcoholic O
substances O
should O
be O
avoided O
. O
For O
each O
patient O
, O
clinical O
chemistry O
and O
ECG O
are O
always O
a O
pre O
- O
requisite O
as O
well O
as O
the O
evaluation O
of O
the O
tetanus O
immunisation O
status O
and O
for O
which O
immunisation O
may O
be O
provided O
if O
needed O
. O
The O
treatment O
of O
any O
clinical O
complication O
, O
due O
to O
the O
envenomation O
, O
does O
not O
differ O
from O
treatments O
of O
emergency O
nature O
. O
Antivenom O
is O
recommended O
when O
signs O
of O
systemic O
envenomation O
exist O
or O
in O
case O
of O
advanced O
local O
or O
systemic O
progressive O
symptoms O
. O
Recommendations O
for O
future O
work O
concludes O
. O
The O
aim O
of O
this O
review O
is O
to O
support O
clinicians O
for O
the O
clinical O
management O
of O
viper O
envenomation O
, O
through O
taxonomic O
keys O
for O
main O
species O
identification O
, O
description O
of O
venom O
composition O
and O
mode O
of O
action O
of O
known O
toxins O
and O
provide O
a O
standardised O
clinical O
protocol O
and O
antivenom O
administration O
. O
Objective O
To O
determine O
the O
incidence B-EPI
, O
time O
trends O
, O
risk O
factors O
, O
and O
severity O
of O
herpes O
zoster O
in O
a O
population O
- O
based O
cohort O
of O
patients O
with O
newly O
diagnosed O
rheumatoid O
arthritis O
( O
RA O
) O
compared O
to O
a O
group O
of O
individuals O
without O
RA O
from O
the O
same O
population O
. O
Methods O
All O
residents O
of O
Olmsted B-LOC
County I-LOC
, O
Minnesota B-LOC
fulfilling O
for O
the O
first O
time O
the O
1987 O
American O
College O
of O
Rheumatology O
criteria O
for O
RA O
between O
January O
1 O
, O
1980 O
and O
December O
31 O
, O
2007 O
and O
a O
cohort O
of O
similar O
residents O
without O
RA O
were O
assembled O
and O
followed O
by O
retrospective O
chart O
review O
until O
death O
, O
migration O
, O
or O
December O
31 O
, O
2008 O
. O
Results O
There O
was O
no O
difference O
in O
the O
presence O
of O
herpes O
zoster O
prior O
to O
the O
RA O
incidence B-EPI
/ O
index O
date O
between O
the O
cohorts O
( O
P O
= O
0.85 O
) O
. O
During O
followup O
, O
84 O
patients O
with O
RA O
( O
rate O
12.1 B-STAT
cases I-STAT
per I-STAT
1,000 I-STAT
person I-STAT
- O
years O
) O
and O
44 O
subjects O
without O
RA O
( O
rate O
5.4 B-STAT
cases I-STAT
per I-STAT
1,000 I-STAT
person I-STAT
- O
years O
) O
developed O
herpes O
zoster O
. O
Patients O
with O
RA O
were O
more O
likely O
to O
develop O
herpes O
zoster O
than O
those O
without O
RA O
( O
hazard O
ratio O
[ O
HR O
] O
2.4 O
[ O
95 O
% O
confidence O
interval O
( O
95 O
% O
CI O
) O
1.7 O
- O
3.5 O
] O
) O
. O
Herpes O
zoster O
occurred O
more O
frequently O
in O
patients O
diagnosed O
with O
RA O
more O
recently O
( O
HR O
1.06 O
per O
year O
[ O
95 O
% O
CI O
1.02 O
- O
1.10 O
] O
) O
. O
Erosive O
disease O
, O
previous O
joint O
surgery O
, O
and O
use O
of O
hydroxychloroquine O
and O
corticosteroids O
were O
significantly O
associated O
with O
the O
development O
of O
herpes O
zoster O
in O
RA O
. O
There O
was O
no O
apparent O
association O
of O
herpes O
zoster O
with O
the O
use O
of O
methotrexate O
or O
biologic O
agents O
. O
Complications O
of O
herpes O
zoster O
occurred O
at O
a O
similar O
rate O
in O
both O
cohorts O
. O
Conclusion O
The O
incidence B-EPI
of O
herpes O
zoster O
is O
increased O
in O
RA O
and O
has O
risen O
in O
recent O
years O
. O
There O
also O
has O
been O
an O
increasing O
incidence B-EPI
of O
herpes O
zoster O
in O
more O
recent O
years O
in O
the O
general O
population O
. O
RA O
disease O
severity O
is O
associated O
with O
the O
development O
of O
herpes O
zoster O
. O
Background O
Little O
information O
is O
available O
about O
the O
incidence B-EPI
of O
stiff O
- O
man O
syndrome O
( O
SMS O
) O
( O
the O
classic O
form O
or O
its O
variants O
) O
or O
about O
long O
- O
term O
treatment O
responses O
and O
outcomes O
. O
Objective O
To O
comprehensively O
describe O
the O
characteristics O
of O
a O
cohort O
of O
patients O
with O
SMS O
. O
Design O
Observational O
study O
. O
Setting O
Mayo O
Clinic O
, O
Rochester B-LOC
, O
Minnesota B-LOC
. O
Patients O
Ninety O
- O
nine O
patients O
with O
classic O
SMS O
vs O
variants O
of O
the O
disorder O
, O
both O
glutamic O
acid O
decarboxylase O
65 O
kD O
isoform O
( O
GAD65 O
) O
antibody O
seropositive O
and O
seronegative O
. O
Main O
outcome O
measures O
Neurological O
, O
autoimmune O
, O
serological O
, O
and O
oncological O
findings O
; O
treatments O
; O
and O
outcomes O
between O
January O
1984 O
and O
December O
2008 O
. O
Results O
The O
median O
follow O
- O
up O
duration O
was O
5 O
years O
( O
range O
, O
0 O
- O
23 O
years O
) O
. O
Seventy O
- O
nine O
patients O
( O
59 O
having O
classic O
SMS O
, O
19 O
having O
partial O
SMS O
, O
and O
1 O
having O
progressive O
encephalomyelitis O
with O
rigidity O
and O
myoclonus O
[ O
PERM O
] O
) O
were O
GAD65 O
antibody O
seropositive O
. O
Sixty B-STAT
- O
seven O
percent O
( O
53 O
of O
79 O
) O
of O
them O
had O
at O
least O
1 O
coexisting O
autoimmune O
disease O
, O
and O
4 O
% O
( O
3 O
of O
79 O
) O
had O
cancer O
. O
GAD65 O
antibody O
values O
at O
initial O
evaluation O
were O
significantly O
higher O
among O
patients O
with O
classic O
SMS O
( O
median O
value O
, O
623 O
nmol O
/ O
L O
) O
than O
among O
patients O
with O
partial O
SMS O
( O
median O
value O
, O
163 O
nmol O
/ O
L O
) O
( O
P O
< O
.001 O
) O
. O
The O
initial O
GAD65 O
antibody O
value O
was O
positively O
correlated O
with O
the O
last O
follow O
- O
up O
Rankin O
score O
( O
P O
= O
.03 O
) O
. O
Among O
20 O
patients O
who O
were O
GAD65 O
antibody O
seronegative O
( O
6 O
with O
classic O
SMS O
, O
12 O
with O
partial O
SMS O
, O
and O
2 O
with O
PERM O
) O
, O
15 O
% O
( O
3 O
of O
20 O
) O
had O
at O
least O
1 O
coexisting O
autoimmune O
disease O
, O
and O
25 O
% O
( O
5 O
of O
20 O
) O
had O
cancer O
( O
3 O
with O
amphiphysin O
autoimmunity O
and O
breast O
carcinoma O
and O
2 O
with O
Hodgkin O
lymphoma O
) O
. O
Excluding O
patients O
with O
PERM O
, O
all O
patients O
but O
1 O
had O
sustained O
improvements O
with O
at O
least O
1 O
γ O
- O
aminobutyric O
acid O
agent O
, O
usually O
diazepam O
; O
the O
median O
dosage O
for O
patients O
with O
classic O
SMS O
was O
40.0 O
mg O
/ O
d. O
Additional O
improvements O
occurred O
among O
14 O
of O
34 O
patients O
( O
41 O
% O
) O
who O
received O
immunotherapy O
( O
intravenous O
immune O
globulin O
, O
azathioprine O
, O
prednisone O
, O
mycophenolate O
mofetil O
, O
or O
cyclophosphamide O
) O
. O
Sixteen O
of O
25 O
patients O
( O
64 O
% O
) O
with O
extended O
follow O
- O
up O
duration O
remained O
ambulatory O
. O
Conclusions O
Recognition O
of O
classic O
SMS O
vs O
variants O
is O
important O
because O
appropriate O
therapy O
improves O
symptoms O
in O
most O
patients O
. O
Classification O
by O
anatomical O
extent O
and O
by O
GAD65 O
antibody O
serostatus O
gives O
important O
diagnostic O
and O
prognostic O
information O
. O
Cutaneous O
squamous O
cell O
carcinoma O
( O
cSCC O
) O
is O
the O
second O
most O
prevalent B-EPI
skin O
cancer O
globally O
. O
Because O
most O
cSCC O
cases O
are O
manageable O
by O
local O
excision O
/ O
radiotherapy O
and O
hardly O
become O
life O
- O
threatening O
, O
they O
are O
often O
excluded O
from O
cancer O
registries O
in O
most O
countries O
. O
Compared O
with O
cutaneous O
melanoma O
that O
originates O
from O
the O
melanin O
- O
producing O
, O
neural O
crest O
- O
derived O
epidermal O
resident O
, O
keratinocyte O
( O
KC)-derived O
cancers O
are O
influenced O
by O
the O
immune O
system O
with O
regards O
to O
their O
pathogenetic O
behaviour O
. O
Congenital O
or O
acquired O
immunosurveillance O
impairments O
compromise O
tumoricidal O
activity O
and O
raises O
cSCC O
incidence B-EPI
rates O
. O
Intriguingly O
, O
expanded O
applications O
of O
programmed O
death-1 O
( O
PD-1 O
) O
blockade O
therapies O
have O
revealed O
cSCC O
to O
be O
one O
of O
the O
most O
amenable O
targets O
, O
particularly O
when O
compared O
with O
the O
mucosal O
counterparts O
arisen O
in O
the O
esophagus O
or O
the O
cervix O
. O
The O
clinical O
observation O
reminds O
us O
that O
cutaneous O
tissue O
has O
a O
peculiarly O
high O
immunogenicity O
that O
can O
evoke O
tumoricidal O
recall O
responses O
topically O
. O
Here O
we O
attempt O
to O
redefine O
cSCC O
biology O
and O
review O
current O
knowledge O
about O
cSCC O
from O
multiple O
viewpoints O
that O
involve O
epidemiology O
, O
clinicopathology O
, O
molecular O
genetics O
, O
molecular O
immunology O
, O
and O
developmental O
biology O
. O
This O
synthesis O
not O
only O
underscores O
the O
primal O
importance O
of O
the O
immune O
system O
, O
rather O
than O
just O
a O
mere O
accumulation O
of O
ultraviolet O
- O
induced O
mutations O
but O
also O
reinforces O
the O
following O
hypothesis O
: O
PD-1 O
blockade O
effectively O
restores O
the O
immunity O
specially O
allowed O
to O
exist O
within O
the O
fully O
cornified O
squamous O
epithelium O
, O
that O
is O
, O
the O
epidermis O
. O
Aim O
To O
investigate O
the O
point O
prevalence B-EPI
of O
hereditary O
neuromuscular O
disorders O
on O
January O
1 O
, O
2020 O
in O
Northern B-LOC
Norway I-LOC
. O
Methods O
From O
January O
1 O
, O
1999 O
, O
until O
January O
1 O
, O
2020 O
, O
we O
screened O
medical O
and O
genetic O
hospital O
records O
in O
Northern B-LOC
Norway I-LOC
for O
hereditary O
neuromuscular O
disorders O
. O
Results O
We O
identified O
542 O
patients O
with O
a O
hereditary O
neuromuscular O
disorder O
living O
in O
Northern B-LOC
Norway I-LOC
, O
giving O
a O
point O
prevalence B-EPI
of O
111.9/100,000 B-STAT
on O
January O
1 O
, O
2020 O
. O
The O
prevalence B-EPI
of O
children O
( O
< O
18 O
years O
old O
) O
and O
adults O
( O
≥18 O
years O
old O
) O
were O
57.8/100,000 B-STAT
and O
125.1/100,000 B-STAT
, O
respectively O
. O
Inherited O
neuropathies O
had O
a O
prevalence B-EPI
of O
38.8/100,000 B-STAT
. O
Charcot O
- O
Marie O
- O
Tooth O
and O
hereditary O
neuropathy O
with O
liability O
to O
pressure O
palsies O
had O
a O
prevalence B-EPI
of O
29.9/100,000 B-STAT
and O
8.3/100,000 B-STAT
, O
respectively O
. O
We O
calculated O
a O
prevalence B-EPI
of O
3.7/100,000 B-STAT
for O
spinal O
muscular O
atrophies O
and O
2.4/100,000 B-STAT
for O
Kennedy O
disease O
. O
Inherited O
myopathies O
were O
found O
in O
67.7/100,000 B-STAT
. O
Among O
these O
, O
we O
registered O
13.4/100,000 B-STAT
myotonic O
dystrophy O
type O
1 B-STAT
, I-STAT
6.8/100,000 I-STAT
myotonic O
dystrophy O
type O
2 B-STAT
, I-STAT
7.3/100,000 I-STAT
Duchenne O
muscular O
dystrophy O
, O
1.6/100,000 B-STAT
Becker O
muscular O
dystrophy O
, O
3.7/100,000 B-STAT
facioscapulohumeral O
muscular O
dystrophy O
, O
12.8/100,000 B-STAT
limb O
- O
girdle O
muscular O
dystrophy O
, O
2.5/100,000 B-STAT
hypokalemic O
periodic O
paralysis O
and O
11.4/100,000 B-STAT
myotonia O
congenita O
. O
Conclusion O
Our O
total O
prevalence B-EPI
was O
higher O
than O
previously O
hypothesized O
in O
European O
population O
- O
based O
studies O
. O
The O
prevalence B-EPI
was O
especially O
high O
for O
myotonia O
congenita O
and O
limb O
- O
girdle O
muscular O
dystrophy O
. O
The O
prevalence B-EPI
of O
Charcot O
- O
Marie O
- O
Tooth O
polyneuropathy O
was O
higher O
than O
in O
most O
European O
studies O
, O
but O
lower O
than O
previously O
reported O
in O
epidemiological O
studies O
in O
other O
regions O
of O
Norway B-LOC
. O
About O
30 O
% O
of O
patients O
with O
MEN1 O
develop O
a O
Zollinger O
- O
Ellison O
syndrome O
. O
Meanwhile O
it O
is O
well O
established O
that O
the O
causative O
gastrinomas O
are O
almost O
exclusively O
localized O
in O
the O
duodenum O
and O
not O
in O
the O
pancreas O
, O
MEN1 O
gastrinomas O
occur O
multicentric O
and O
are O
associated O
with O
hyperplastic O
gastrin O
cell O
lesions O
and O
tiny O
gastrin O
- O
producing O
micro O
tumors O
in O
contrast O
to O
sporadic O
duodenal O
gastrinomas O
. O
Regardless O
of O
the O
high O
prevalence B-EPI
of O
early O
lymphatic O
metastases O
, O
the O
survival O
is O
generally O
good O
with O
an O
aggressive O
course O
of O
disease O
in O
only O
about O
20 B-STAT
% O
of O
patients O
. O
Symptoms O
can O
be O
controlled O
medically O
. O
The O
indication O
, O
timing O
, O
type O
, O
and O
extent O
of O
surgery O
are O
highly O
controversial O
and O
are O
discussed O
in O
detail O
in O
this O
article O
by O
a O
thorough O
and O
critical O
review O
of O
literature O
. O
More O
radical O
procedures O
, O
like O
partial O
pancreaticoduodenectomy O
, O
are O
weighed O
against O
less O
aggressive O
local O
excision O
of O
gastrinomas O
and O
the O
pros O
and O
cons O
of O
both O
approaches O
are O
discussed O
in O
terms O
of O
long O
- O
term O
morbidity O
, O
biochemical O
cure O
, O
and O
survival O
. O
The O
review O
lists O
the O
genetic O
diseases O
reported O
in O
Lebanese O
individuals O
, O
surveys O
genetic O
programs O
and O
services O
, O
and O
highlights O
the O
absence O
of O
basic O
genetic O
health O
services O
at O
the O
individual O
and O
community O
level O
. O
The O
incidence B-EPI
of O
individual O
diseases O
is O
not O
determined O
, O
yet O
the O
variety O
of O
genetic O
diseases O
reported O
is O
tremendous O
, O
most O
of O
which O
follow O
autosomal O
recessive O
inheritance O
reflecting O
the O
social O
norms O
in O
the O
population O
, O
including O
high O
rates O
of O
consanguinity O
, O
which O
favor O
the O
increase O
in O
incidence B-EPI
of O
these O
diseases O
. O
Genetic O
services O
including O
all O
activities O
for O
the O
diagnosis O
, O
care O
, O
and O
prevention O
of O
genetic O
diseases O
at O
community O
level O
are O
extremely O
inadequate O
. O
Services O
are O
limited O
to O
some O
clinical O
and O
laboratory O
diagnostic O
services O
with O
no O
genetic O
counseling O
. O
These O
services O
are O
localized O
within O
the O
capital O
thus O
preventing O
their O
accessibility O
to O
high O
- O
risk O
communities O
. O
Screening O
programs O
, O
which O
are O
at O
the O
core O
of O
public O
health O
prevention O
services O
, O
are O
minimal O
and O
not O
nationally O
mandated O
. O
The O
absence O
of O
adequate O
genetic O
services O
is O
attributed O
to O
many O
factors O
undermining O
the O
importance O
of O
genetic O
diseases O
and O
their O
burden O
on O
society O
, O
the O
most O
important O
of O
which O
is O
genetic O
illiteracy O
at O
all O
levels O
of O
the O
population O
, O
including O
high O
- O
risk O
families O
, O
the O
general O
public O
, O
and O
most O
importantly O
health O
care O
providers O
and O
public O
health O
officials O
. O
Thus O
, O
a O
country O
like O
Lebanon B-LOC
, O
where O
genetic O
diseases O
are O
expected O
to O
be O
highly O
prevalent B-EPI
, O
is O
in O
utmost O
need O
for O
community O
genetics O
services O
. O
Strategies O
need O
to O
be O
developed O
to O
familiarize O
public O
health O
officials O
and O
medical O
professionals O
with O
medical O
genetics O
leading O
to O
a O
public O
health O
infrastructure O
that O
delivers O
community O
genetics O
services O
for O
the O
prevention O
and O
care O
of O
genetic O
disorders O
at O
community O
level O
. O
Background O
Congenital O
malformations O
involving O
the O
Müllerian O
ducts O
are O
observed O
in O
around O
5 O
% O
of O
infertile O
women O
. O
Complete O
aplasia O
of O
the O
uterus O
, O
cervix O
, O
and O
upper O
vagina O
, O
also O
termed O
Müllerian O
aplasia O
or O
Mayer O
- O
Rokitansky O
- O
Kuster O
- O
Hauser O
( O
MRKH O
) O
syndrome O
, O
occurs B-EPI
with O
an O
incidence B-EPI
of O
around O
1 B-STAT
in I-STAT
4500 I-STAT
female I-STAT
births I-STAT
, O
and O
occurs B-EPI
in O
both O
isolated O
and O
syndromic O
forms O
. O
Previous O
reports O
have O
suggested O
that O
a O
proportion O
of O
cases O
, O
especially O
syndromic O
cases O
, O
are O
caused O
by O
variation O
in O
copy O
number O
at O
different O
genomic O
loci O
. O
Methods O
In O
order O
to O
obtain O
an O
overview O
of O
the O
contribution O
of O
copy O
number O
variation O
to O
both O
isolated O
and O
syndromic O
forms O
of O
Müllerian O
aplasia O
, O
copy O
number O
assays O
were O
performed O
in O
a O
series O
of O
63 O
cases O
, O
of O
which O
25 O
were O
syndromic O
and O
38 O
isolated O
. O
Results O
A O
high O
incidence B-EPI
( O
9/63 B-STAT
, O
14 O
% O
) O
of O
recurrent O
copy O
number O
variants O
in O
this O
cohort O
is O
reported O
here O
. O
These O
comprised O
four O
cases O
of O
microdeletion O
at O
16p11.2 O
, O
an O
autism O
susceptibility O
locus O
not O
previously O
associated O
with O
Müllerian O
aplasia O
, O
four O
cases O
of O
microdeletion O
at O
17q12 O
, O
and O
one O
case O
of O
a O
distal O
22q11.2 O
microdeletion O
. O
Microdeletions O
at O
16p11.2 O
and O
17q12 O
were O
found O
in O
4/38 B-STAT
( O
10.5 O
% O
) O
cases O
with O
isolated O
Müllerian O
aplasia O
, O
and O
at O
16p11.2 O
, O
17q12 O
and O
22q11.2 O
( O
distal O
) O
in O
5/25 B-STAT
cases O
( O
20 O
% O
) O
with O
syndromic O
Müllerian O
aplasia O
. O
Conclusion O
The O
finding O
of O
microdeletion O
at O
16p11.2 O
in O
2/38 B-STAT
( O
5 O
% O
) O
of O
isolated O
and O
2/25 B-STAT
( O
8 O
% O
) O
of O
syndromic O
cases O
suggests O
a O
significant O
contribution O
of O
this O
copy O
number O
variant O
alone O
to O
the O
pathogenesis O
of O
Müllerian O
aplasia O
. O
Overall O
, O
the O
high O
incidence B-EPI
of O
recurrent O
copy O
number O
variants O
in O
all O
forms O
of O
Müllerian O
aplasia O
has O
implications O
for O
the O
understanding O
of O
the O
aetiopathogenesis O
of O
the O
condition O
, O
and O
for O
genetic O
counselling O
in O
families O
affected O
by O
it O
. O
The O
parkinsonian O
syndromes O
comprise O
a O
highly O
heterogeneous O
group O
of O
disorders O
. O
Although O
15 O
loci O
are O
linked O
to O
predominantly O
familial O
Parkinson O
's O
disease O
( O
PD O
) O
, O
additional O
PD O
loci O
are O
likely O
to O
exist O
. O
We O
recently O
identified O
a O
multigenerational O
family O
of O
Danish O
and O
German O
descent O
in O
which O
five O
males O
in O
three O
generations O
presented O
with O
a O
unique O
syndrome O
characterized O
by O
parkinsonian O
features O
and O
variably O
penetrant O
spasticity O
for O
which O
X O
- O
linked O
disease O
transmission O
was O
strongly O
suggested O
( O
XPDS O
) O
. O
Autopsy O
in O
one O
individual O
failed O
to O
reveal O
synucleinopathy O
; O
however O
, O
there O
was O
a O
significant O
four O
- O
repeat O
tauopathy O
in O
the O
striatum O
. O
Our O
objective O
was O
to O
identify O
the O
locus O
responsible O
for O
this O
unique O
parkinsonian O
disorder O
. O
Members O
of O
the O
XPDS O
family O
were O
genotyped O
for O
markers O
spanning O
the O
X O
chromosome O
. O
Two O
- O
point O
and O
multipoint O
linkage O
analyses O
were O
performed O
and O
the O
candidate O
region O
refined O
by O
analyzing O
additional O
markers O
. O
A O
multipoint O
LOD(max O
) O
score O
of O
2.068 O
was O
obtained O
between O
markers O
DXS991 O
and O
DXS993 O
. O
Haplotype O
examination O
revealed O
an O
approximately O
20 O
cM O
region O
bounded O
by O
markers O
DXS8042 O
and O
DXS1216 O
that O
segregated O
with O
disease O
in O
all O
affected O
males O
and O
obligate O
carrier O
females O
and O
was O
not O
carried O
by O
unaffected O
at O
- O
risk O
males O
. O
To O
reduce O
the O
possibility O
of O
a O
false O
- O
positive O
linkage O
result O
, O
multiple O
loci O
and O
genes O
associated O
with O
other O
parkinsonian O
or O
spasticity O
syndromes O
were O
excluded O
. O
In O
conclusion O
, O
we O
have O
identified O
a O
unique O
X O
- O
linked O
parkinsonian O
syndrome O
with O
variable O
spasticity O
and O
four O
- O
repeat O
tau O
pathology O
, O
and O
defined O
a O
novel O
candidate O
gene O
locus O
spanning O
approximately O
28 O
Mb O
from O
Xp11.2 O
- O
Xq13.3 O
. O
Background O
Most O
epidemiological O
data O
on O
vitiligo O
refer O
to O
selected O
environments O
or O
focus O
on O
the O
prevalence B-EPI
of O
comorbidity O
unrelated O
to O
the O
population O
. O
Objective O
Aim O
of O
the O
study O
was O
to O
gain O
robust O
representative O
prevalence B-EPI
data O
on O
vitiligo O
and O
on O
associated O
dermatologic O
comorbidity O
in O
the O
German O
adult O
population O
. O
Methods O
A O
dual O
population O
- O
based O
approach O
was O
applied O
with O
1 O
) O
primary O
data O
obtained O
between O
2004 O
and O
2014 O
from O
dermatological O
exams O
in O
the O
general O
working O
population O
; O
2 O
) O
claims O
data O
from O
a O
large O
German O
statutory O
health O
insurance O
, O
reference O
year O
2010 O
. O
Results O
In O
the O
working O
cohort O
( O
N O
= O
121,783 O
; O
57 O
% O
male O
; O
mean O
age O
43 O
years O
) O
, O
the O
prevalence B-EPI
of O
vitiligo O
was O
0.77 B-STAT
% I-STAT
( O
0.84 B-STAT
% I-STAT
in O
men O
; O
0.67 B-STAT
% I-STAT
in O
women O
) O
. O
In O
the O
claims O
data O
( O
N O
= O
1,619,678 O
; O
38 O
% O
male O
; O
mean O
age O
46 O
years O
) O
, O
prevalence B-EPI
was O
0.17 B-STAT
% I-STAT
( O
0.14 B-STAT
% I-STAT
in O
men O
; O
0.18 B-STAT
% I-STAT
in O
women O
) O
. O
In O
the O
working O
cohort O
, O
vitiligo O
was O
significantly O
more O
common O
in O
people O
with O
fair O
skin O
type O
, O
ephelides O
and O
port O
- O
wine O
stains O
and O
less O
common O
in O
people O
with O
acne O
and O
solar O
lentigines O
. O
In O
the O
claims O
data O
, O
vitiligo O
was O
associated O
with O
a O
variety O
of O
skin O
conditions O
, O
eg O
, O
atopic O
dermatitis O
, O
psoriasis O
and O
alopecia O
areata O
. O
Conclusion O
The O
resulting O
discrepancy O
of O
claims O
vs O
primary O
data O
between O
0.17 B-STAT
% I-STAT
and O
0.77 B-STAT
% I-STAT
indicates O
the O
most O
probable O
spectrum O
of O
vitiligo O
prevalence B-EPI
in O
Germany B-LOC
. O
It O
is O
more O
frequently O
observed O
in O
clinical O
exams O
than O
recorded O
in O
claims O
data O
, O
indicating O
a O
marked O
proportion O
of O
people O
seeking O
no O
medical O
help O
. O
Such O
nonattendance O
may O
result O
from O
the O
fact O
that O
many O
treatment O
options O
do O
not O
provide O
satisfying O
benefits O
to O
the O
patients O
. O
Background O
Unilateral O
lung O
agenesis O
is O
an O
uncommon O
congenital O
abnormality O
, O
with O
a O
lack O
of O
reported O
accurate O
incidence B-EPI
estimates O
. O
Prognosis O
is O
also O
uncertain O
, O
with O
older O
literature O
reporting O
poor O
outcomes O
. O
Methods O
The O
North O
of O
England O
register O
of O
congenital O
anomalies O
( O
Northern O
Congenital O
Abnormality O
Survey O
) O
records O
cases O
of O
congenital O
anomalies O
to O
mothers O
' O
resident O
in O
the O
region O
. O
We O
used O
the O
register O
to O
identify O
all O
patients O
with O
congenital O
lung O
agenesis O
born O
between O
2004 O
and O
2013 O
to O
calculate O
an O
accurate O
incidence B-EPI
estimate O
and O
report O
clinical O
outcomes O
with O
contemporary O
management O
. O
Results O
Four O
patients O
with O
congenital O
lung O
agenesis O
were O
born O
during O
the O
study O
period O
, O
giving O
an O
estimated B-EPI
incidence I-EPI
in O
the B-LOC
North I-LOC
of I-LOC
England I-LOC
of O
1.22 B-STAT
per I-STAT
100,000 I-STAT
live I-STAT
births I-STAT
( O
95 O
% O
confidence O
interval O
, O
0.33 O
- O
3.11 O
) O
. O
Two O
patients O
had O
associated O
congenital O
heart O
disease O
requiring O
corrective O
surgery O
, O
and O
one O
had O
musculoskeletal O
anomalies O
. O
All O
four O
patients O
are O
alive O
and O
well O
without O
a O
regular O
oxygen O
requirement O
. O
Conclusion O
Contrary O
to O
previous O
reports O
, O
the O
medium O
term O
outcomes O
in O
our O
patients O
have O
been O
good O
, O
even O
when O
lung O
agenesis O
is O
associated O
with O
other O
congenital O
anomalies O
. O
Long O
- O
term O
prognosis O
with O
modern O
management O
remains O
unknown O
, O
and O
the O
potential O
for O
the O
development O
of O
pulmonary O
hypertension O
remains O
a O
concern O
. O
Birth O
Defects O
Research O
109:857 B-STAT
- O
859 O
, O
2017 O
. O
© O
2017 O
Wiley O
Periodicals O
, O
Inc. O
The O
disease O
and O
the O
case O
reported O
here O
are O
relevant O
especially O
because O
of O
their O
varied O
clinical O
presentation O
, O
possibility O
of O
being O
associated O
with O
other O
disorders O
affecting O
several O
organs O
and O
possible O
differential O
diagnoses O
. O
Congenital O
Hepatic O
Fibrosis O
is O
an O
autosomal O
recessive O
disease O
due O
to O
mutation O
in O
the O
PKHD1 O
gene O
, O
which O
encodes O
the O
fibrocystin O
/ O
polyductine O
protein O
. O
It O
is O
a O
cholangiopathy O
, O
characterized O
by O
varying O
degrees O
of O
periportal O
fibrosis O
and O
irregular O
proliferation O
of O
bile O
ducts O
. O
Affected O
patients O
are O
typically O
diagnosed O
in O
childhood O
, O
but O
in O
some O
cases O
the O
disease O
may O
remain O
asymptomatic O
for O
many O
years O
. O
The O
exact O
prevalence B-EPI
and O
incidence B-EPI
of O
the O
disease O
are O
not O
known O
, O
but O
it O
is O
consider O
a O
rare O
disease O
, O
with O
a O
few O
hundred O
cases O
described O
worldwide B-LOC
. O
It O
can O
affect O
all O
ethnic O
groups O
and O
occur O
associated O
with O
various O
hereditary O
and O
non O
- O
hereditary O
disorders O
. O
The O
clinical O
presentation O
is O
quite O
variable O
, O
with O
melena O
and O
hematemesis O
being O
initial O
symptoms O
in O
30%-70 O
% O
of O
the O
cases O
. O
More O
rarely O
, O
they O
may O
present O
episodes O
of O
cholangitis O
. O
The O
disease O
has O
been O
classified O
into O
four O
types O
: O
portal O
hypertension O
, O
cholestasis O
/ O
cholangitis O
, O
mixed O
and O
latent O
. O
Diagnosis O
begins O
with O
imaging O
tests O
, O
but O
the O
definition O
is O
made O
by O
the O
histopathological O
sample O
. O
So O
far O
, O
there O
is O
no O
specific O
therapy O
that O
can O
stop O
or O
reverse O
the O
pathological O
process O
. O
Currently O
, O
the O
therapeutic O
strategy O
is O
to O
treat O
the O
complications O
of O
the O
disease O
. O
Impetigo O
is O
a O
common O
superficial O
bacterial O
infection O
of O
the O
skin O
, O
with O
a O
global O
disease O
burden O
of O
greater O
than O
140 O
million O
. O
Children O
are O
more O
affected O
than O
adults O
and O
incidence B-EPI
decreases O
with O
age O
. O
Principal O
pathogens O
implicated O
include O
Staphylococcus O
aureus O
and O
Streptococcus O
pyogenes O
. O
There O
are O
two O
common O
variants O
of O
impetigo O
: O
nonbullous O
( O
70 O
% O
) O
and O
bullous O
( O
30 O
% O
) O
. O
Nonbullous O
impetigo O
is O
caused O
by O
S. O
aureus O
and O
S. O
pyogenes O
whereas O
bullous O
impetigo O
is O
caused O
by O
S. O
aureus O
. O
The O
classic O
appearance O
of O
distinctive O
honey O
- O
colored O
, O
crusted O
legions O
aids O
in O
diagnosis O
, O
which O
is O
most O
often O
based O
on O
clinical O
presentation O
. O
The O
disease O
is O
generally O
mild O
and O
felt O
to O
be O
self O
- O
limited O
; O
however O
, O
antimicrobial O
treatment O
is O
often O
initiated O
to O
reduce O
spread O
and O
shorten O
clinical O
course O
. O
Treatment O
for O
limited O
impetigo O
is O
topical O
whereas O
oral O
therapy O
is O
recommended O
for O
extensive O
cases O
. O
Rising O
rates O
of O
bacterial O
resistance O
to O
standard O
treatment O
regimens O
should O
inform O
treatment O
decisions O
. O
Complications O
, O
while O
rare O
, O
can O
occur O
. O
Congenital O
hearing O
loss O
is O
the O
most O
common O
birth O
defect O
, O
estimated O
to O
affect O
2 O
- O
3 O
in O
every O
1000 O
births O
. O
Currently O
there O
is O
no O
cure O
for O
hearing O
loss O
. O
Treatment O
options O
are O
limited O
to O
hearing O
aids O
for O
mild O
and O
moderate O
cases O
, O
and O
cochlear O
implants O
for O
severe O
and O
profound O
hearing O
loss O
. O
Here O
we O
provide O
a O
literature O
overview O
of O
the O
environmental O
and O
genetic O
causes O
of O
congenital O
hearing O
loss O
, O
common O
animal O
models O
and O
methods O
used O
for O
hearing O
research O
, O
as O
well O
as O
recent O
advances O
towards O
developing O
therapies O
to O
treat O
congenital O
deafness O
. O
© O
2021 O
The O
Authors O
. O
Background O
Infection O
with O
Entamoeba O
histolytica O
and O
associated O
complications O
are O
relatively O
rare O
in O
developed O
countries O
. O
The O
overall O
low O
prevalence B-EPI
in O
the O
Western O
world O
as O
well O
as O
the O
possibly O
prolonged O
latency O
period O
between O
infection O
with O
the O
causing O
pathogen O
and O
onset O
of O
clinical O
symptoms O
may O
delay O
diagnosis O
of O
and O
adequate O
treatment O
for O
amoebiasis O
. O
Amoebic O
liver O
abscess O
( O
ALA O
) O
is O
the O
most O
common O
extraintestinal O
manifestation O
of O
invasive O
amoebiasis O
. O
Pregnancy O
has O
been O
described O
as O
a O
risk O
factor O
for O
development O
of O
invasive O
amoebiasis O
and O
management O
of O
these O
patients O
is O
especially O
complex O
. O
Case O
presentation O
A O
30 O
- O
year O
- O
old O
Caucasian O
woman O
in O
early O
pregnancy O
presented O
to O
our O
emergency O
department O
with O
abdominal O
pain O
alongside O
elevated O
inflammatory O
markers O
and O
liver O
function O
tests O
. O
Travel O
history O
revealed O
multiple O
journeys O
to O
tropic O
and O
subtropic O
regions O
during O
the O
past O
decade O
and O
a O
prolonged O
episode O
of O
intermittently O
bloody O
diarrhea O
during O
a O
five O
month O
stay O
in O
Indonesia B-LOC
seven O
years O
prior O
to O
admission O
. O
Sonographic O
and O
magnetic O
resonance O
imaging O
revealed O
a O
5 O
× O
4 O
cm O
hepatic O
abscess O
. O
After O
ultrasound O
- O
guided O
transcutaneous O
liver O
drainage O
, O
both O
abscess O
fluids O
and O
blood O
cultures O
showed O
neither O
bacterial O
growth O
nor O
microscopic O
signs O
of O
parasitic O
disease O
. O
Serological O
testing O
confirmed O
an O
infection O
with O
Entamoeba O
histolytica O
, O
which O
was O
treated O
with O
metronidazole O
, O
followed O
by O
eradication O
therapy O
with O
paromomycin O
. O
Subsequent O
clinical O
, O
laboratory O
and O
imaging O
follow O
- O
up O
exams O
showed O
regression O
of O
the O
ALA O
. O
In O
addition O
, O
the O
pregnancy O
completed O
without O
complications O
and O
a O
healthy O
baby O
boy O
was O
born O
7 O
months O
after O
termination O
of O
treatment O
. O
Conclusions O
This O
case O
of O
invasive O
amoebiasis O
in O
early O
pregnancy O
outside O
of O
endemic O
regions O
and O
several O
years O
after O
exposure O
demonstrates O
the O
importance O
of O
broad O
differential O
diagnostics O
in O
the O
context O
of O
liver O
abscesses O
. O
The O
complex O
interdisciplinary O
decisions O
regarding O
the O
choice O
of O
imaging O
techniques O
as O
well O
as O
interventional O
and O
antibiotic O
therapy O
in O
the O
context O
of O
pregnancy O
are O
discussed O
. O
Furthermore O
, O
we O
present O
possible O
explanations O
for O
pregnancy O
as O
a O
risk O
factor O
for O
an O
invasive O
course O
of O
amoebiasis O
. O
Objective O
Myotonia O
Congenita O
( O
MC O
) O
is O
a O
hereditary O
neuromuscular O
disorder O
caused O
by O
a O
mutation O
in O
chloride O
voltage O
- O
gated O
channel O
1 O
( O
CLCN1 O
) O
gene O
. O
The O
incidence B-EPI
of O
MC O
is O
estimated O
as O
1 O
in O
100.000 O
. O
The O
absence O
of O
left O
main O
coronary O
artery O
( O
LMCA O
) O
is O
a O
rare O
coronary O
anomaly O
. O
Here O
we O
present O
a O
family O
with O
four O
members O
who O
have O
MC O
variation O
carrier O
and O
cardiovascular O
risk O
. O
Method O
The O
demographic O
features O
, O
laboratory O
findings O
, O
anthropometric O
measurements O
and O
cardiological O
examination O
of O
the O
cases O
were O
recorded O
. O
In O
addition O
, O
CLCN1 O
gene O
was O
sequenced O
by O
NGS O
( O
Next O
Generation O
Sequencing O
Method O
) O
and O
possible O
causes O
of O
inherited O
thrombophilia O
risk O
including O
MTHFR O
( O
A1298C O
) O
, O
Factor O
V O
Leiden O
( O
G1691A O
) O
, O
Factor O
II O
( O
G20210A O
) O
, O
MTHFR O
( O
C677 O
T O
) O
, O
Factor O
V O
Cambridge O
( O
G1091C O
) O
, O
plasminogen O
activator O
inhibitor O
1 O
( O
PAI-1 O
) O
4G/5 B-STAT
G O
, O
APOE O
, O
APOB O
, O
ITGB O
, O
ACE O
( O
ins O
/ O
del O
) O
, O
FVHR2 O
and O
FGB O
gene O
alterations O
were O
evaluated O
. O
Results O
Case O
1 O
had O
homozygous O
c.1886T O
> O
C O
( O
p. O
Leu629Pro O
) O
alteration O
in O
CLCN1 O
gene O
and O
also O
coronary O
artery O
disease O
, O
myocardial O
infarction O
( O
MI O
) O
history O
, O
hyperlipidemia O
, O
primary O
hypertension O
, O
vertigo O
, O
lomber O
disc O
herniation O
and O
hearing O
loss O
. O
LMCA O
was O
not O
detected O
in O
coronary O
angiography O
in O
Case O
1 O
. O
Cases O
2 O
, O
3 O
and O
4 O
had O
heterozygous O
c.1886T O
> O
C O
( O
p. O
Leu629Pro O
) O
alteration O
with O
normal O
electrocardiographic O
and O
echocardiographic O
findings O
. O
Additionally O
, O
all O
of O
family O
members O
had O
genetic O
risk O
factors O
for O
the O
related O
gene O
, O
which O
lead O
to O
an O
increased O
risk O
of O
cardiovascular O
disease O
. O
Conclusion O
Since O
alteration O
of O
chloride O
channels O
in O
cardiomyocytes O
leads O
to O
variable O
myocardial O
involvement O
, O
cases O
with O
MC O
should O
be O
regularly O
followed O
for O
cardiovascular O
risk O
. O
Moreover O
, O
the O
cases O
with O
MC O
and O
with O
genetic O
profile O
associated O
with O
high O
cardiovascular O
risk O
should O
also O
be O
regularly O
followed O
up O
by O
cardiologists O
. O
Bubonic O
plague O
has O
caused O
three O
deadly O
pandemics O
in O
human O
history O
: O
from O
the O
mid O
- O
sixth O
to O
mid O
- O
eighth O
century O
, O
from O
the O
mid O
- O
fourteenth O
to O
the O
mid O
- O
eighteenth O
century O
and O
from O
the O
end O
of O
the O
nineteenth O
until O
the O
mid O
- O
twentieth O
century O
. O
Between O
the O
second O
and O
the O
third O
pandemics O
, O
plague O
was O
causing O
sporadic O
outbreaks O
in O
only O
a O
few O
countries O
in O
the B-LOC
Middle I-LOC
East I-LOC
, O
including O
Egypt B-LOC
. O
Little O
is O
known O
about O
this O
historical O
phase O
of O
plague O
, O
even O
though O
it O
represents O
the O
temporal O
, O
geographical O
and O
phylogenetic O
transition O
between O
the O
second O
and O
third O
pandemics O
. O
Here O
we O
analysed O
in O
detail O
an O
outbreak O
of O
plague O
that O
took O
place O
in O
Cairo B-LOC
in O
1801 O
, O
and O
for O
which O
epidemiological O
data O
are O
uniquely O
available O
thanks O
to O
the O
presence O
of O
medical O
officers O
accompanying O
the O
Napoleonic O
expedition O
into O
Egypt B-LOC
at O
that O
time O
. O
We O
propose O
a O
new O
stochastic O
model O
describing O
how O
bubonic O
plague O
outbreaks O
unfold O
in O
both O
rat O
and O
human O
populations O
, O
and O
perform O
Bayesian O
inference O
under O
this O
model O
using O
a O
particle O
Markov O
chain O
Monte O
Carlo O
. O
Rat O
carcasses O
were O
estimated O
to O
be O
infectious O
for O
approximately O
4 O
days O
after O
death O
, O
which O
is O
in O
good O
agreement O
with O
local O
observations O
on O
the O
survival O
of O
infectious O
rat O
fleas O
. O
The O
estimated O
transmission O
rate O
between O
rats O
implies O
a O
basic O
reproduction O
number O
R O
0 O
of O
approximately O
3 O
, O
causing O
the O
collapse O
of O
the O
rat O
population O
in O
approximately O
100 O
days O
. O
Simultaneously O
, O
the O
force O
of O
infection O
exerted O
by O
each O
infected O
rat O
carcass O
onto O
the O
human O
population O
increases O
progressively O
by O
more O
than O
an O
order O
of O
magnitude O
. O
We O
also O
considered O
human O
- O
to O
- O
human O
transmission O
via O
pneumonic O
plague O
or O
human O
specific O
vectors O
, O
but O
found O
this O
route O
to O
account O
for O
only O
a O
small O
fraction O
of O
cases O
and O
to O
be O
significantly O
below O
the O
threshold O
required O
to O
sustain O
an O
outbreak O
. O
The O
Quebec O
Neonatal O
Urine O
Screening O
Program O
was O
initiated O
in O
1971 O
with O
overall O
screening O
inception O
of O
newborns O
in O
1973 O
. O
Forty O
- O
seven O
years O
later O
, O
over O
3.5 O
million O
babies O
have O
been O
screened O
for O
up O
to O
25 O
inborn O
errors O
of O
metabolism O
divided O
into O
two O
groups O
: O
( O
1 O
) O
urea O
cycle O
disorders O
and O
organic O
acidurias O
; O
and O
( O
2 O
) O
disorders O
of O
amino O
acid O
metabolism O
and O
transport O
. O
The O
main O
goal O
of O
this O
preventive O
genetic O
medicine O
program O
is O
the O
detection O
of O
treatable O
diseases O
before O
the O
onset O
of O
clinical O
symptoms O
. O
Urine O
specimens O
from O
21 O
- O
day O
- O
old O
babies O
are O
collected O
and O
dried O
on O
filter O
paper O
by O
parents O
at O
home O
. O
The O
participation O
is O
voluntary O
with O
a O
high O
compliance O
rate O
over O
the O
years O
( O
~90 O
% O
) O
. O
Specimens O
are O
analyzed O
by O
thin O
layer O
chromatography O
( O
TLC O
) O
. O
The O
main O
objective O
of O
this O
evaluative O
research O
project O
was O
to O
assess O
the O
feasibility O
of O
a O
technological O
upgrade O
towards O
mass O
spectrometry O
. O
A O
2.85 O
- O
min O
flow O
injection O
method O
was O
devised O
, O
normal O
values O
established O
, O
and O
abnormal O
profiles O
confirmed O
using O
second O
- O
tier O
tests O
. O
The O
validated O
assays O
are O
sensitive O
, O
specific O
, O
and O
suitable O
for O
populational O
screening O
, O
as O
well O
as O
for O
high O
- O
risk O
screening O
laboratories O
. O
Triple O
H O
syndrome O
, O
which O
would O
not O
be O
detected O
in O
newborns O
by O
blood O
screening O
at O
two O
days O
of O
age O
was O
found O
to O
be O
positive O
in O
the O
urine O
of O
an O
affected O
patient O
. O
Objective O
The O
diagnosis O
of O
childhood O
- O
onset O
cerebellar O
ataxia O
( O
CA O
) O
is O
often O
challenging O
due O
to O
variations O
in O
symptoms O
and O
etiologies O
. O
Despite O
the O
known O
regional O
differences O
in O
the O
prevalence B-EPI
of O
etiologies O
underlying O
CA O
, O
the O
frequency O
and O
characteristics O
of O
CA O
in O
Japan B-LOC
remain O
unclear O
. O
We O
conducted O
a O
questionnaire O
- O
based O
survey O
to O
identify O
the O
clinical O
characteristics O
of O
childhood O
- O
onset O
CA O
in O
the O
Japanese O
population O
. O
Materials O
and O
methods O
Questionnaires O
were O
sent O
to O
1,103 O
board O
- O
certified O
pediatric O
neurologists O
in O
Japan B-LOC
from O
2016 O
to O
2017 O
. O
The O
primary O
survey O
requested O
the O
number O
of O
patients O
with O
CA O
under O
care O
, O
and O
the O
follow O
- O
up O
secondary O
questionnaire O
requested O
additional O
clinical O
characteristics O
of O
the O
patients O
. O
Results O
The O
primary O
survey O
obtained O
578 O
responses O
( O
response O
rate O
, O
52.4 O
% O
) O
on O
385 O
patients O
with O
CA O
, O
including O
171 O
diagnosed O
and O
214 O
undiagnosed O
cases O
( O
diagnostic O
rate O
, O
44.4 O
% O
) O
. O
The O
most O
frequent O
etiology O
was O
dentatorubropallidoluysian O
atrophy O
( O
DRPLA O
) O
, O
followed O
by O
mitochondrial O
disorders O
and O
encephalitis O
. O
The O
secondary O
survey O
obtained O
the O
clinical O
characteristics O
of O
252 O
cases O
( O
119 O
diagnosed O
and O
133 O
undiagnosed O
cases O
) O
. O
Multiple O
logistic O
regression O
analysis O
revealed O
that O
a O
younger O
age O
at O
onset O
, O
hearing O
issues O
, O
and O
short O
stature O
were O
associated O
with O
a O
higher O
risk O
of O
remaining O
undiagnosed O
with O
CA O
in O
Japan B-LOC
. O
Conclusions O
The O
diagnostic O
rate O
of O
childhood O
- O
onset O
CA O
in O
the O
current O
study O
was O
comparable O
to O
those O
reported O
in O
other O
countries O
. O
The O
high O
prevalence B-EPI
of O
autosomal O
dominant O
ataxia O
, O
especially O
DRPLA O
, O
was O
a O
signature O
of O
CA O
in O
Japan B-LOC
. O
These O
data O
offer O
insights O
into O
the O
characteristics O
of O
childhood O
- O
onset O
CA O
in O
the O
Japanese O
population O
. O
Early O
detection O
of O
disabling O
diseases O
, O
prior O
to O
clinical O
manifestations O
, O
is O
the O
primary O
goal O
of O
newborn O
screening O
( O
NS O
) O
. O
Indeed O
, O
the O
required O
number O
of O
core O
and O
secondary O
conditions O
selected O
for O
screening O
panels O
is O
increasing O
in O
many O
countries O
. O
Furthermore O
, O
newborn O
screening O
can O
lead O
to O
diagnosis O
of O
maternal O
diseases O
such O
as O
vitamin O
B12 O
deficiency O
or O
3 O
- O
MethylcrotonylCoA O
- O
carboxylase O
deficiency O
( O
3MCC O
) O
. O
NS O
became O
mandatory O
in O
Sicily B-LOC
in O
December O
2017 O
. O
Here O
we O
report O
NS O
data O
collected O
between O
December O
2017 O
and O
April O
2020 O
. O
Our O
results O
show O
that O
tandem O
mass O
spectrometry O
is O
a O
powerful O
tool O
for O
discovery O
of O
underestimated O
disease O
in O
newborns O
and O
their O
family O
members O
. O
Our O
panel O
included O
short O
chain O
acyl O
- O
CoA O
dehydrogenase O
deficiency O
( O
SCADD O
) O
. O
Here O
, O
we O
report O
that O
results O
of O
our O
investigation O
led O
to O
reassessment O
of O
SCADD O
prevalence B-EPI
in O
our O
population O
. O
The O
infant O
and O
adult O
patients O
diagnosed O
in O
our O
study O
had O
previously O
not O
shown O
overt O
symptoms O
. O
Allogeneic O
islet O
transplantation O
is O
a O
standard O
of O
care O
treatment O
for O
patients O
with O
labile O
type O
1 O
diabetes O
in O
many O
countries O
around O
the O
world O
, O
including O
Japan B-LOC
, O
the B-LOC
United I-LOC
Kingdom I-LOC
, O
Australia B-LOC
, O
much O
of O
continental O
Europe B-LOC
, O
and O
parts O
of O
Canada B-LOC
. O
The B-LOC
United I-LOC
States I-LOC
is O
now O
endorsing O
islet O
cell O
treatment O
for O
type O
1 O
diabetes O
, O
but O
the O
FDA O
has O
chosen O
to O
consider O
islets O
as O
a O
biologic O
that O
requires O
licensure O
, O
making O
the O
universal O
implementation O
of O
the O
procedure O
in O
the O
clinic O
very O
challenging O
and O
opening O
the O
manufacture O
of O
islet O
grafts O
to O
private O
companies O
. O
The O
commercialization O
of O
human O
tissues O
raises O
significant O
legal O
and O
ethical O
issues O
and O
ironically O
leads O
to O
a O
situation O
where O
treatments O
developed O
as O
a O
result O
of O
the O
scientific O
and O
economic O
efforts O
of O
academia O
over O
several O
decades O
become O
exploited O
exclusively O
by O
for O
- O
profit O
entities O
. O
Background O
Many O
public O
health O
surveillance O
programs O
utilize O
hospital O
discharge O
data O
in O
their O
estimation O
of O
disease O
prevalence B-EPI
. O
These O
databases O
commonly O
use O
the O
International O
Classification O
of O
Diseases O
( O
ICD O
) O
coding O
scheme O
, O
which O
transitioned O
from O
the O
ICD-9 O
clinical O
modification O
( O
ICD-9 O
- O
CM O
) O
to O
ICD-10 O
- O
CM O
on O
October O
1 O
, O
2015 O
. O
This O
study O
examined O
this O
transition O
's O
impact O
on O
the O
prevalence B-EPI
of O
major O
birth O
defects O
among O
infant O
hospitalizations O
. O
Methods O
Using O
data O
from O
the O
Agency O
for O
Health O
Care O
Research O
and O
Quality O
- O
sponsored O
National O
Inpatient O
Sample O
, O
hospitalizations O
during O
the O
first O
year O
of O
life O
with O
a O
discharge O
date O
between O
January O
1 O
, O
2012 O
and O
December O
31 O
, O
2016 O
were O
used O
to O
estimate O
the O
monthly O
national O
hospital O
prevalence B-EPI
of O
46 O
birth O
defects O
for O
the O
ICD-9 O
- O
CM O
and O
ICD-10 O
- O
CM O
timeframes O
separately O
. O
Survey O
- O
weighted O
Poisson O
regression O
was O
used O
to O
estimate O
95 O
% O
confidence O
intervals O
for O
each O
hospital O
prevalence B-EPI
. O
Interrupted O
time O
series O
framework O
and O
corresponding O
segmented O
regression O
was O
used O
to O
estimate O
the O
immediate O
change O
in O
monthly O
hospital O
prevalence B-EPI
following O
the O
ICD-9 O
- O
CM O
to O
ICD-10 O
- O
CM O
transition O
. O
Results O
Between O
2012 O
and O
2016 O
, O
over O
21 O
million O
inpatient O
hospitalizations O
occurred O
during O
the O
first O
year O
of O
life O
. O
Among O
the O
46 O
defects O
studied O
, O
statistically O
significant O
decreases O
in O
the O
immediate O
hospital O
prevalence B-EPI
of O
five O
defects O
and O
significant O
increases O
in O
the O
immediate O
hospital O
prevalence B-EPI
of O
eight O
defects O
were O
observed O
after O
the O
ICD-10 O
- O
CM O
transition O
. O
Conclusions O
Changes O
in O
prevalence B-EPI
were O
expected O
based O
on O
changes O
to O
ICD-10 O
- O
CM O
. O
Observed O
changes O
for O
some O
conditions O
may O
result O
from O
variation O
in O
monthly O
hospital O
prevalence B-EPI
or O
initial O
unfamiliarity O
of O
coders O
with O
ICD-10 O
- O
CM O
. O
These O
findings O
may O
help O
birth O
defects O
surveillance O
programs O
evaluate O
and O
interpret O
changes O
in O
their O
data O
related O
to O
the O
ICD-10 O
- O
CM O
transition O
. O
Juvenile O
Idiopathic O
Arthritis O
is O
one O
of O
the O
most O
prevalent B-EPI
chronic O
diseases O
in O
children O
, O
with O
an O
annual B-EPI
incidence I-EPI
of O
2 B-STAT
- I-STAT
20 I-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
and I-STAT
a O
prevalence B-EPI
of O
16 B-STAT
- I-STAT
150 I-STAT
per I-STAT
100,000 I-STAT
. O
It O
is O
associated O
with O
several O
complications O
that O
can O
cause O
short O
- O
term O
or O
long O
- O
term O
disability O
and O
reduce O
the O
quality O
of O
life O
. O
Among O
these O
, O
growth O
and O
pubertal O
disorders O
play O
an O
important O
role O
. O
Chronic O
inflammatory O
conditions O
are O
often O
associated O
with O
growth O
failure O
ranging O
from O
slight O
decrease O
in O
height O
velocity O
to O
severe O
forms O
of O
short O
stature O
. O
The O
prevalence B-EPI
of O
short O
stature O
in O
JIA O
varies O
from O
10.4 O
% O
in O
children O
with O
polyarticular O
disease B-STAT
to O
41 O
% O
of O
patients O
with O
the O
systemic O
form O
, O
while O
oligoarthritis O
is O
mostly O
associated O
with O
localized O
excessive O
bone O
growth O
of O
the O
affected O
limb O
, O
leading O
to O
limb O
dissymmetry O
. O
The O
pathogenesis O
of O
growth O
disorders O
is O
multifactorial O
and O
includes O
the O
role O
of O
chronic O
inflammation O
, O
long O
- O
term O
use O
of O
corticosteroids O
, O
undernutrition O
, O
altered O
body O
composition O
, O
delay O
of O
pubertal O
onset O
or O
slow O
pubertal O
progression O
. O
These O
factors O
can O
exert O
a O
systemic O
effect O
on O
the O
GH O
/ O
IGF-1 O
axis O
and O
on O
the O
GnRH O
- O
gonadotropin O
- O
gonadic O
axis O
, O
or O
a O
local O
influence O
on O
the O
growth O
plate O
homeostasis O
and O
function O
. O
Although O
new O
therapeutic O
options O
are O
available O
to O
control O
inflammation O
, O
there O
are O
still O
10 B-STAT
- O
20 O
% O
of O
patients O
with O
severe O
forms O
of O
the O
disease O
who O
show O
continuous O
growth O
impairment O
, O
ending O
in O
a O
short O
final O
stature O
. O
Moreover O
, O
delayed O
puberty O
is O
associated O
with O
a O
reduction O
in O
the O
peak O
bone O
mass O
with O
the O
possibility O
of O
concomitant O
or O
future O
bone O
fragility O
. O
Monitoring O
of O
puberty O
and O
bone O
health O
is O
essential O
for O
a O
complete O
health O
assessment O
of O
adolescents O
with O
JIA O
. O
In O
these O
patients O
, O
an O
assessment O
of O
the O
pubertal O
stage O
every O
6 O
months O
from O
the O
age O
of O
9 O
years O
is O
recommended O
. O
Also O
, O
linear O
growth O
should O
be O
always O
evaluated O
considering O
the O
patient O
's O
bone O
age O
. O
The O
impact O
of O
rhGH O
therapy O
in O
children O
with O
JIA O
is O
still O
unclear O
, O
but O
it O
has O
been O
shown O
that O
if O
rhGH O
is O
added O
at O
high O
dose O
in O
a O
low O
- O
inflammatory O
condition O
, O
post O
steroids O
and O
on O
biologic O
therapy O
, O
it O
is O
able O
to O
favor O
a O
prepubertal O
growth O
acceleration O
, O
comparable O
with O
the O
catch O
- O
up O
growth O
response O
in O
GH O
- O
deficient O
patients O
. O
Here O
we O
provide O
a O
comprehensive O
review O
of O
the O
pathogenesis O
of O
puberty O
and O
growth O
disorders O
in O
children O
with O
JIA O
, O
which O
can O
help O
the O
pediatrician O
to O
properly O
and O
timely O
assess O
the O
presence O
of O
growth O
and O
pubertal O
disorders O
in O
JIA O
patients O
. O
Neonatal O
herpes O
simplex O
virus O
( O
HSV O
) O
infection O
is O
rare O
, O
with O
an O
estimated B-EPI
incidence I-EPI
of O
3.58 B-STAT
per I-STAT
100 I-STAT
000 I-STAT
live I-STAT
births I-STAT
in O
the O
UK B-LOC
and O
should O
be O
suspected O
in O
any O
newborn O
with O
fever O
and O
bacterial O
culture O
- O
negative O
sepsis O
. O
We O
describe O
a O
case O
of O
a O
previously O
well O
full O
- O
term O
male O
neonate O
who O
presented O
with O
persistent O
fever O
and O
elevated O
ferritin O
level O
that O
was O
carried O
out O
during O
the O
era O
of O
the O
COVID-19 O
pandemic O
as O
part O
of O
SARS O
- O
CoV-2 O
panel O
investigations O
. O
Despite O
the O
initial O
negative O
HSV O
serology O
, O
HSV-1 O
PCR O
from O
a O
scalp O
lesion O
returned O
positive O
. O
He O
made O
a O
full O
recovery O
after O
acyclovir O
therapy O
. O
This O
case O
highlights O
the O
importance O
of O
maintaining O
a O
high O
clinical O
index O
of O
suspicion O
of O
HSV O
infection O
in O
any O
febrile O
neonate O
even O
with O
absence O
of O
maternal O
history O
and O
negative O
serology O
, O
particularly O
if O
associated O
with O
hyperferritinaemia O
. O
We O
also O
address O
the O
challenge O
of O
interpreting O
inflammatory O
biomarkers O
' O
results O
for O
SARS O
- O
CoV-2 O
infection O
in O
neonates O
. O
Herpes O
zoster O
oticus O
also O
known O
as O
Ramsay O
Hunt O
syndrome O
is O
a O
rare O
complication O
of O
herpes O
zoster O
in O
which O
reactivation O
of O
latent O
varicella O
zoster O
virus O
infection O
in O
the O
geniculate O
ganglion O
causes O
otalgia O
, O
auricular O
vesicles O
, O
and O
peripheral O
facial O
paralysis O
. O
Ramsay O
Hunt O
syndrome O
is O
rare O
in O
children O
and O
affects O
both O
sexes O
equally O
. O
Incidence B-EPI
and O
clinical O
severity O
increases O
when O
host O
immunity O
is O
compromised O
. O
Because O
these O
symptoms O
do O
not O
always O
present O
at O
the O
onset O
, O
this O
syndrome O
can O
be O
misdiagnosed O
. O
Although O
secondary O
to O
Bell O
's O
palsy O
in O
terms O
of O
the O
cause O
of O
acute O
atraumatic O
peripheral O
facial O
paralysis O
, O
Ramsay O
Hunt O
syndrome O
, O
with O
incidence B-EPI
ranged O
from O
0.3 B-STAT
to O
18 O
% O
, O
has O
a O
worse O
prognosis O
. O
Herpes O
zoster O
oticus O
accounts O
for O
about O
12 O
% O
cases O
of O
facial O
palsy O
, O
which O
is O
usually O
unilateral O
and O
complete O
and O
full O
recovery O
occurs B-EPI
in O
only O
about O
20 B-STAT
% O
of O
untreated O
patients O
. O
The O
most O
advisable O
method O
to O
treat O
Ramsay O
Hunt O
syndrome O
is O
the O
combination O
therapy O
with O
acyclovir O
and O
prednisone O
but O
still O
not O
promising O
, O
and O
several O
prerequisites O
are O
required O
for O
better O
results O
. O
We O
present O
a O
case O
of O
32 O
- O
year O
- O
old O
man O
suffering O
from O
Ramsay O
Hunt O
syndrome O
with O
grade O
V O
facial O
palsy O
treated O
effectively O
with O
rehabilitation O
program O
, O
after O
the O
termination O
of O
the O
combination O
therapy O
of O
acyclovir O
and O
prednisone O
. O
The O
May O
- O
Hegglin O
anomaly O
is O
characterized O
by O
inherited O
thrombocytopenia O
, O
giant O
platelets O
, O
and O
leukocyte O
cytoplasmic O
inclusion O
bodies O
. O
The O
Fechtner O
, O
Sebastian O
, O
and O
Epstein O
syndromes O
are O
associated O
with O
mutations O
of O
the O
MYH9 O
- O
coding O
nonmuscle O
myosin O
heavy O
chain O
ⅡA O
, O
similar O
to O
the O
May O
- O
Hegglin O
anomaly O
, O
and O
are O
together O
classified O
as O
MYH9 O
disorders O
. O
MYH9 O
disorders O
may O
include O
symptoms O
of O
Alport O
syndrome O
, O
including O
nephritis O
and O
auditory O
and O
ocular O
disorders O
. O
A O
6 O
- O
year O
- O
old O
boy O
was O
diagnosed O
with O
an O
MYH9 O
disorder O
after O
incidental O
discovery O
of O
hematuria O
and O
proteinuria O
. O
Focal O
segmental O
glomerulosclerosis O
was O
detected O
on O
renal O
biopsy O
. O
However O
, O
despite O
no O
prior O
bleeding O
diatheses O
, O
he O
developed O
a O
large O
post O
- O
biopsy O
hematoma O
despite O
a O
preprocedural O
platelet O
transfusion O
calculated O
to O
increase O
the O
platelet O
count O
from O
54,000 O
/ O
μL O
to O
> O
150,000 O
/ O
μL. O
Idiopathic O
thrombocytopenic O
purpura O
is O
a O
major O
cause O
of O
pediatric O
thrombocytopenia O
following O
acute O
infection O
or O
vaccination O
, O
and O
patients O
with O
MYH9 O
disorders O
may O
be O
misdiagnosed O
with O
idiopathic O
thrombocytopenic O
purpura O
and O
inappropriately O
treated O
with O
corticosteroids O
. O
Careful O
differential O
diagnosis O
is O
important O
in O
thrombocytopenic O
patients O
with O
hematuria O
and O
proteinuria O
for O
the O
early O
detection O
of O
thrombocytopenia O
. O
Patients O
with O
MYH9 O
disorders O
require O
close O
follow O
- O
up O
and O
treatment O
with O
angiotensin O
Ⅱ O
receptor O
blockers O
to O
prevent O
the O
onset O
of O
progressive O
nephritis O
, O
which O
may O
necessitate O
hemodialysis O
or O
renal O
transplantation O
. O
The O
need O
for O
renal O
biopsy O
in O
patients O
with O
MYH9 O
disorders O
should O
be O
carefully O
considered O
because O
there O
could O
be O
adverse O
outcomes O
even O
after O
platelet O
transfusion O
. O
Ehlers O
- O
Danlos O
Syndrome O
( O
EDS O
) O
is O
a O
family O
of O
multisystemic O
hereditary O
connective O
tissue O
disorders O
now O
comprised O
of O
13 O
recognized O
subtypes O
, O
classical O
, O
classical O
- O
like O
, O
cardiac O
- O
valvular O
, O
vascular O
, O
hypermobile O
, O
arthrochlasia O
, O
dermosparaxis O
, O
kyphoscoliotic O
, O
brittle O
cornea O
syndrome O
, O
spondylodysplastic O
, O
musculocontractural O
, O
myopathic O
, O
and O
periodontal O
, O
as O
designated O
by O
the O
most O
recent O
2017 O
International O
classification O
system O
. O
Clinical O
presentation O
of O
this O
disease O
can O
range O
from O
mild O
manifestations O
including O
skin O
hyperextensibility O
and O
joint O
hypermobility O
, O
to O
more O
severe O
complications O
such O
as O
vascular O
and O
organ O
rupture O
. O
While O
there O
may O
be O
accompanying O
inflammation O
in O
some O
of O
the O
subtypes O
of O
EDS O
, O
the O
pathogenic O
mechanisms O
have O
not O
been O
clearly O
defined O
. O
Thorough O
evaluation O
incorporates O
clinical O
examination O
, O
family O
history O
, O
laboratory O
testing O
, O
and O
imaging O
. O
In O
recent O
years O
, O
studies O
have O
identified O
multiple O
gene O
variants O
involved O
in O
the O
pathogenesis O
of O
specific O
EDS O
subtypes O
as O
well O
as O
elaborate O
clinical O
diagnostic O
criteria O
and O
classification O
models O
used O
to O
differentiate O
overlapping O
conditions O
. O
The O
differential O
diagnosis O
of O
EDS O
includes O
hypermobility O
spectrum O
disorders O
, O
Marfan O
syndrome O
, O
Loey O
- O
Dietz O
syndrome O
, O
Cutis O
laxa O
syndromes O
, O
autosomal O
dominant O
polycystic O
kidney O
disease O
, O
osteogenesis O
Imperfecta O
Type O
1 O
, O
fibromyalgia O
, O
depression O
, O
and O
chronic O
fatigue O
syndrome O
. O
Surgical O
treatment O
is O
reserved O
for O
complications O
, O
or O
emergencies O
involving O
vascular O
or O
orthopedic O
injury O
because O
of O
the O
risk O
of O
poor O
wound O
healing O
. O
Management O
techniques O
each O
have O
their O
own O
consequences O
and O
benefits O
, O
which O
will O
also O
be O
discussed O
in O
this O
review O
article O
. O
Patients O
affected O
by O
this O
spectrum O
of O
disorders O
are O
impacted O
both O
phenotypically O
and O
psychosocially O
, O
diminishing O
their O
quality O
of O
life O
. O
Objective O
To O
study O
the O
genetic O
cause O
of O
Mayer O
- O
Rokitansky O
- O
Kuster O
- O
Hauser O
syndrome O
( O
MRKH O
) O
. O
Although O
a O
few O
candidate O
genes O
and O
genomic O
domains O
for O
have O
been O
reported O
for O
MRKH O
, O
the O
genetic O
underpinnings O
remain O
largely O
unknown O
. O
Some O
of O
the O
top O
candidate O
genes O
are O
WNT4 O
, O
HNF1B B-LOC
, O
and O
LHX1 O
. O
The O
goals O
of O
this O
study O
were O
to O
: O
1 O
) O
determine O
the O
prevalence B-EPI
of O
WNT4 O
, O
HNF1B B-LOC
, O
and O
LHX1 O
point O
mutations O
, O
as O
well O
as O
new O
copy O
number O
variants O
( O
CNVs O
) O
in O
people O
with O
MRKH O
; O
and O
2 O
) O
identify O
and O
characterize O
MRKH O
cohorts O
. O
Design O
Laboratory- O
and O
community O
- O
based O
study O
. O
Setting O
Academic O
medical O
centers O
. O
Patient(s O
) O
A O
total O
of O
147 O
MRKH O
probands O
and O
available O
family O
members O
. O
Interventions(s O
) O
DNA O
sequencing O
of O
WNT4 O
, O
HNF1B B-LOC
, O
and O
LHX1 O
in O
100 O
MRKH O
patients O
, O
chromosomal O
microarray O
analysis O
in O
31 O
North O
American O
MRKH O
patients O
, O
and O
characterization O
and O
sample O
collection O
of O
147 O
North O
American O
and O
Turkish O
MRKH O
probands O
and O
their O
families O
. O
Main O
outcome O
measure(s O
) O
DNA O
sequence O
variants O
and O
CNVs O
; O
pedigree O
structural O
analysis O
. O
Result(s O
) O
We O
report O
finding O
CNVs O
in O
6/31 B-STAT
people O
( O
∼19 O
% O
) O
with O
MRKH O
, O
but O
no O
point O
mutations O
or O
small O
indels O
in O
WNT4 O
, O
HNF1B B-LOC
, O
or O
LHX1 O
in O
100 O
MRKH O
patients O
. O
Our O
MRKH O
families O
included O
43 O
quads O
, O
26 O
trios O
, O
and O
30 O
duos O
. O
Of O
our O
MRKH O
probands O
, O
87/147 B-STAT
( O
59 O
% O
) O
had O
MRKH O
type O
1 B-STAT
and I-STAT
60/147 I-STAT
( O
41 O
% O
) O
had O
type O
2 O
with O
additional O
anomalies O
. O
Conclusion(s O
) O
Although O
the O
prevalence B-EPI
of O
WNT4 O
, O
HNF1B B-LOC
, O
and O
LHX1 O
point O
mutations O
is O
low O
in O
people O
with O
MRKH O
, O
the O
prevalence B-EPI
of O
CNVs O
was O
∼19 O
% O
. O
Further O
analysis O
of O
our O
large O
familial O
cohort O
of O
patients O
will O
facilitate O
gene O
discovery O
to O
better O
understand O
the O
complex O
etiology O
of O
MRKH O
. O
A O
novel O
coronavirus O
SARS O
- O
CoV-2 O
causing O
Coronavirus O
disease O
2019 O
( O
COVID-19 O
) O
has O
entered O
the O
human O
population O
and O
has O
spread O
rapidly O
around O
the O
world O
in O
the O
first O
half O
of O
2020 O
causing O
a O
global O
pandemic O
. O
The O
virus O
uses O
its O
spike O
glycoprotein O
receptor O
- O
binding O
domain O
to O
interact O
with O
host O
cell O
angiotensin O
- O
converting O
enzyme O
2 O
( O
ACE2 O
) O
sites O
to O
initiate O
a O
cascade O
of O
events O
that O
culminate O
in O
severe O
acute O
respiratory O
syndrome O
in O
some O
individuals O
. O
In O
efforts O
to O
curtail O
viral O
spread O
, O
authorities O
initiated O
far O
- O
reaching O
lockdowns O
that O
have O
disrupted O
global O
economies O
. O
The O
scientific O
and O
medical O
communities O
are O
mounting O
serious O
efforts O
to O
limit O
this O
pandemic O
and O
subsequent O
waves O
of O
viral O
spread O
by O
developing O
preventative O
vaccines O
and O
repurposing O
existing O
drugs O
as O
potential O
therapies O
. O
In O
this O
review O
, O
we O
focus O
on O
the O
latest O
developments O
in O
COVID-19 O
vaccine O
development O
, O
including O
results O
of O
the O
first O
Phase O
I O
clinical O
trials O
and O
describe O
a O
number O
of O
the O
early O
candidates O
that O
are O
emerging O
in O
the O
field O
. O
We O
seek O
to O
provide O
a O
balanced O
coverage O
of O
the O
seven O
main O
platforms O
used O
in O
vaccine O
development O
that O
will O
lead O
to O
a O
desired O
target O
product O
profile O
for O
the O
O
ideal O
O
vaccine O
. O
Using O
tales O
of O
past O
vaccine O
discovery O
efforts O
that O
have O
taken O
many O
years O
or O
that O
have O
failed O
, O
we O
temper O
over O
exuberant O
enthusiasm O
with O
cautious O
optimism O
that O
the O
global O
medical O
community O
will O
reach O
the O
elusive O
target O
to O
treat O
COVID-19 O
and O
end O
the O
pandemic O
. O
Background O
Many O
epidemiological O
studies O
have O
indicated O
that O
inbreeding O
has O
little O
or O
no O
effect O
on O
the O
incidence B-EPI
of O
cancer O
. O
Due O
to O
the O
high O
prevalence B-EPI
of O
consanguinity O
in O
Qatar B-LOC
( O
54 O
% O
) O
, O
its O
influence O
may O
nevertheless O
be O
of O
special O
importance O
. O
Aim O
The O
aim O
of O
this O
study O
was O
to O
examine O
whether O
parental O
consanguinity O
affects O
the O
risk O
of O
cancer O
in O
a O
local O
Arab O
highly O
inbred O
population O
. O
Design O
Matched O
case O
- O
control O
study O
. O
Setting O
The O
study O
was O
carried O
out O
in O
Al O
- O
Amal O
cancer O
hospital O
and O
primary O
health O
care O
centers O
in O
Qatar B-LOC
over O
a O
period O
from O
August O
2008 O
to O
February O
2009 O
. O
Subjects O
and O
methods O
The O
study O
included O
370 O
Qataris O
and O
other O
Arab O
expatriates O
with O
various O
types O
of O
cancers O
and O
635 O
controls O
matched O
by O
age O
and O
ethnicity O
. O
A O
questionnaire O
that O
included O
socio O
- O
demographic O
information O
, O
type O
of O
consanguinity O
, O
medical O
history O
, O
and O
tumor O
grade O
was O
designed O
to O
collect O
the O
information O
of O
cases O
and O
controls O
. O
Results O
The O
study O
revealed O
that O
the O
rate O
of O
parental O
consanguinity O
was O
similar O
in O
both O
cases O
( O
29.5 O
% O
) O
and O
controls O
( O
29.9 O
% O
) O
with O
a O
higher O
inbreeding O
coefficient O
in O
controls O
( O
0.017-/+0.03 B-STAT
) O
, O
compared O
to O
cancer O
patients O
( O
0.0155-/+0.03 B-STAT
) O
. O
Other O
Arab O
expatriates O
had O
a O
higher O
incidence B-EPI
of O
cancer O
( O
61.1 O
% O
) O
than O
Qataris O
( O
38.9 O
% O
) O
. O
The O
inbreeding O
coefficient O
was O
higher O
in O
male O
cancer O
patients O
( O
0.0189-/+0.03 B-STAT
) O
, O
but O
lower O
in O
female O
cancer O
patients O
( O
0.014-/+0.03 B-STAT
) O
as O
compared O
to O
controls O
. O
Controls O
were O
more O
inbred O
in O
the O
overall O
studied O
subjects O
( O
23.6 O
% O
) O
and O
women O
( O
23.8 O
% O
) O
than O
cases O
. O
The O
coefficient O
of O
inbreeding O
was O
lower O
in O
patients O
with O
breast O
( O
0.014 O
) O
, O
skin O
( O
0.012 O
) O
, O
thyroid O
( O
0.008 O
) O
and O
female O
genital O
( O
0.014 O
) O
cancers O
, O
whereas O
it O
was O
higher O
in O
cases O
for O
leukemia O
and O
lymphoma O
( O
0.018 O
) O
, O
colorectal O
( O
0.025 O
) O
and O
prostate O
( O
0.017 O
) O
, O
with O
no O
significant O
difference O
between O
cases O
and O
controls O
. O
No O
significant O
differences O
were O
observed O
between O
cases O
and O
controls O
in O
the O
parental O
consanguinity O
, O
mean O
coefficient O
of O
inbreeding O
and O
proportion O
of O
more O
inbred O
subjects O
. O
Conclusions O
The O
study O
findings O
revealed O
that O
although O
the O
consanguinity O
rate O
is O
high O
in O
our O
Arab O
population O
, O
it O
has O
no O
effect O
on O
the O
incidence B-EPI
of O
cancers O
overall O
. O
However O
, O
there O
was O
an O
increased O
risk O
found O
for O
leukemia O
and O
lymphoma O
, O
colorectal O
and O
prostate O
cancer O
groups O
, O
but O
a O
reduced O
risk O
in O
breast O
, O
skin O
, O
thyroid O
and O
female O
genital O
cancer O
groups O
. O
Anaphylaxis O
is O
a O
severe O
allergic O
reaction O
, O
rapid O
in O
onset O
, O
and O
can O
lead O
to O
fatal O
consequences O
if O
not O
promptly O
treated O
. O
The O
incidence B-EPI
of O
anaphylaxis O
has O
risen O
at O
an O
alarming O
rate O
in O
past O
decades O
and O
continues O
to O
rise O
. O
Therefore O
, O
there O
is O
a O
general O
interest O
in O
understanding O
the O
molecular O
mechanism O
that O
leads O
to O
an O
exacerbated O
response O
. O
The O
main O
effector O
cells O
are O
mast O
cells O
, O
commonly O
triggered O
by O
stimuli O
that O
involve O
the O
IgE O
- O
dependent O
or O
IgE O
- O
independent O
pathway O
. O
These O
signaling O
pathways O
converge O
in O
the O
release O
of O
proinflammatory O
mediators O
, O
such O
as O
histamine O
, O
tryptases O
, O
prostaglandins O
, O
etc O
. O
, O
in O
minutes O
. O
The O
action O
and O
cell O
targets O
of O
these O
proinflammatory O
mediators O
are O
linked O
to O
the O
pathophysiologic O
consequences O
observed O
in O
this O
severe O
allergic O
reaction O
. O
While O
many O
molecules O
are O
involved O
in O
cellular O
regulation O
, O
the O
expression O
and O
regulation O
of O
transcription O
factors O
involved O
in O
the O
synthesis O
of O
proinflammatory O
mediators O
and O
secretory O
granule O
homeostasis O
are O
of O
special O
interest O
, O
due O
to O
their O
ability O
to O
control O
gene O
expression O
and O
change O
phenotype O
, O
and O
they O
may O
be O
key O
in O
the O
severity O
of O
the O
entire O
reaction O
. O
In O
this O
review O
, O
we O
will O
describe O
our O
current O
understanding O
of O
the O
pathophysiology O
of O
human O
anaphylaxis O
, O
focusing O
on O
the O
transcription O
factors O
' O
contributions O
to O
this O
systemic O
hypersensitivity O
reaction O
. O
Host O
mutation O
in O
transcription O
factor O
expression O
, O
or O
deregulation O
of O
their O
activity O
in O
an O
anaphylaxis O
context O
, O
will O
be O
updated O
. O
So O
far O
, O
the O
risk O
of O
anaphylaxis O
is O
unpredictable O
thus O
, O
increasing O
our O
knowledge O
of O
the O
molecular O
mechanism O
that O
leads O
and O
regulates O
mast O
cell O
activity O
will O
enable O
us O
to O
improve O
our O
understanding O
of O
how O
anaphylaxis O
can O
be O
prevented O
or O
treated O
. O
Background O
Childhood O
alopecia O
areata O
( O
AA O
) O
is O
a O
common O
cause O
of O
dermatologic O
consultation O
; O
however O
, O
data O
is O
scarce O
in O
the O
present O
set O
- O
up O
. O
Objectives O
To O
evaluate O
the O
clinico O
- O
epidemiological O
profile O
of O
childhood O
AA O
along O
with O
dermoscopic O
correlation O
. O
Methods O
We O
conducted O
a O
cross O
- O
sectional O
study O
including O
50 O
new O
cases O
of O
childhood O
AA O
for O
1 O
year O
. O
Dermoscopy O
was O
performed O
in O
each O
child O
and O
findings O
recorded O
. O
Results O
Childhood O
AA O
was O
more O
common O
in O
girls O
( O
M O
: O
F O
1:1.4 O
) O
, O
mean O
age O
being O
11.1 O
± O
3.7 O
years O
. O
Scalp O
was O
commonest O
site O
of O
involvement O
in O
86 O
% O
cases O
, O
while O
32 B-STAT
( O
64 O
% O
) O
children O
had O
mild O
disease O
( O
< O
25 O
% O
involvement O
) O
. O
Localized O
circumscribed O
patch O
was O
the O
commonest O
presentation O
in O
37 B-STAT
( O
74 O
% O
) O
children O
, O
while O
sisaipho O
was O
the O
least O
( O
2 O
% O
) O
. O
A O
positive O
family O
history O
of O
AA O
was O
noted O
in O
5 B-STAT
( O
10 O
% O
) O
children O
. O
Twenty O
- O
four O
children O
( O
48 O
% O
) O
provided O
a O
history O
of O
atopic O
disorders O
, O
while O
30 O
% O
had O
a O
positive O
family O
history O
of O
atopy O
. O
Stress O
was O
the O
commonest O
precipitating O
factor O
in O
13 B-STAT
( O
26 O
% O
) O
subjects O
. O
Nail O
involvement O
was O
observed O
in O
19 B-STAT
( O
38 O
% O
) O
children O
( O
pitting O
> O
thinning O
) O
, O
while O
systemic O
associations O
like O
vitiligo O
and O
thyroid O
dysfunction O
were O
present O
in O
26 O
% O
and O
24 O
% O
cases O
, O
respectively O
. O
Dermoscopy O
revealed O
yellow O
- O
dots O
to O
be O
the O
commonest O
finding O
in O
44 B-STAT
( O
88 O
% O
) O
cases O
, O
followed O
by O
short O
vellus O
hair O
and O
black O
dots O
in O
76 O
% O
and O
28 O
% O
children O
, O
respectively O
, O
while O
exclamation O
- O
mark O
hair O
was O
rare O
. O
Conclusion O
Female O
gender O
, O
younger O
age O
, O
nail O
involvement O
, O
and O
presence O
of O
concomitant O
atopy O
, O
vitiligo O
, O
and O
thyroid O
dysfunction O
were O
associated O
with O
severe O
disease O
, O
but O
not O
statistically O
significant O
( O
p O
> O
0.05 O
) O
. O
Regression O
model O
failed O
to O
detect O
any O
risk O
factors O
for O
severe O
AA O
. O
Dermoscopy O
is O
an O
important O
non O
- O
invasive O
tool O
for O
evaluating O
childhood O
AA O
. O
Friedreich O
ataxia O
( O
FA O
) O
represents O
the O
most O
frequent O
type O
of O
inherited O
ataxia O
. O
Most O
patients O
carry O
homozygous O
GAA O
expansions O
in O
the O
first O
intron O
of O
the O
frataxin O
gene O
on O
chromosome O
9 O
. O
Due O
to O
epigenetic O
alterations O
, O
frataxin O
expression O
is O
significantly O
reduced O
. O
Frataxin O
is O
a O
mitochondrial O
protein O
. O
Its O
deficiency O
leads O
to O
mitochondrial O
iron O
overload O
, O
defective O
energy O
supply O
and O
generation O
of O
reactive O
oxygen O
species O
. O
This O
review O
gives O
an O
overview O
over O
clinical O
and O
genetic O
aspects O
of O
FA O
and O
discusses O
current O
concepts O
of O
frataxin O
biogenesis O
and O
function O
as O
well O
as O
new O
therapeutic O
strategies O
. O
Diastrophic O
dysplasia O
( O
DTD O
) O
is O
a O
rare O
osteochondrodysplasia O
characterized O
by O
short O
- O
limbed O
short O
stature O
and O
joint O
dysplasia O
. O
DTD O
is O
caused O
by O
mutations O
in O
SLC26A2 O
and O
is O
particularly O
common O
in O
the O
Finnish O
population O
. O
However O
, O
the O
disease O
incidence B-EPI
in O
Finland B-LOC
and O
clinical O
features O
in O
affected O
individuals O
have O
not O
been O
recently O
explored O
. O
This O
registry O
- O
based O
study O
aimed O
to O
investigate O
the O
current O
incidence B-EPI
of O
DTD O
in O
Finland B-LOC
, O
characterize O
the O
national O
cohort O
of O
pediatric O
subjects O
with O
DTD O
and O
review O
the O
disease O
- O
related O
literature O
. O
Subjects O
with O
SLC26A2 O
-related O
skeletal O
dysplasia O
, O
born O
between O
2000 O
and O
2020 O
, O
were O
identified O
from O
the O
Skeletal O
dysplasia O
registry O
and O
from O
hospital O
patient O
registry O
and O
their O
clinical O
and O
molecular O
data O
were O
reviewed O
. O
Fourteen O
subjects O
were O
identified O
. O
Twelve O
of O
them O
were O
phenotypically O
classified O
as O
DTD O
and O
two O
, O
as O
recessive O
multiple O
epiphyseal O
dysplasia O
( O
rMED O
) O
. O
From O
the O
subjects O
with O
available O
genetic O
data O
, O
75 O
% O
( O
9/12 O
) O
were O
homozygous O
for O
the O
Finnish O
founder O
mutation O
c.-26 O
+ O
2T O
> O
C. O
Two O
subjects O
with O
rMED O
phenotype O
were O
compound O
heterozygous O
for O
p. O
Arg279Trp O
and O
p. O
Thr512Lys O
variants O
. O
The O
variable O
phenotypes O
in O
our O
cohort O
highlight O
the O
wide O
spectrum O
of O
clinical O
features O
, O
ranging O
from O
a O
very O
severe O
form O
of O
DTD O
to O
milder O
forms O
of O
DTD O
and O
rMED O
. O
The O
incidence B-EPI
of O
DTD O
in O
Finland B-LOC
has O
significantly O
decreased O
over O
the O
past O
decades O
, O
most O
likely O
due O
to O
increased O
prenatal O
diagnostics O
. O
The O
relationship O
between O
autoinflammatory O
and O
autoimmune O
conditions O
has O
been O
demonstrated O
in O
recent O
decades O
. O
Several O
autoimmune O
conditions O
exhibit O
an O
autoinflammatory O
component O
, O
which O
can O
manifest O
in O
various O
ways O
. O
Neutrophilic O
dermatosis O
in O
the O
context O
of O
lupus O
erythematosus O
( O
LE O
) O
is O
one O
example O
. O
Otherwise O
, O
neutrophils O
are O
rare O
in O
LE O
, O
except O
for O
the O
bullous O
variant O
and O
nonbullous O
neutrophilic O
LE O
. O
In O
this O
paper O
, O
we O
describe O
a O
case O
of O
scarring O
alopecia O
due O
to O
LE O
that O
stopped O
responding O
to O
a O
treatment O
that O
had O
been O
effective O
for O
years O
. O
The O
biopsy O
specimen O
demonstrated O
the O
presence O
of O
neutrophils O
in O
the O
inflammatory O
infiltrate O
. O
A O
treatment O
with O
dapsone O
was O
prescribed O
and O
yielded O
rapid O
improvement O
. O
This O
first O
case O
of O
scarring O
alopecia O
in O
the O
context O
of O
nonbullous O
neutrophilic O
LE O
emphasizes O
the O
importance O
of O
the O
infiltrate O
in O
determining O
the O
optimal O
therapeutic O
choice O
. O
Aims O
Medullary O
carcinoma O
is O
an O
uncommon O
colorectal O
tumour O
which O
appears O
poorly O
differentiated O
histologically O
. O
Consequently O
, O
it O
may O
be O
confused O
with O
poorly O
differentiated O
adenocarcinoma O
not O
otherwise O
specified O
( O
NOS O
) O
. O
The O
principal O
aim O
of O
this O
study O
was O
to O
review O
a O
large O
series O
of O
poorly O
differentiated O
colorectal O
cancers O
resected O
at O
a O
large O
National O
Health O
Service O
( O
NHS O
) O
Teaching O
Hospital O
to O
determine O
how O
often O
medullary O
carcinomas O
were O
misclassified O
. O
Secondary O
aims O
were O
to O
investigate O
how O
often O
neuroendocrine O
differentiation O
or O
metastatic O
tumours O
were O
considered O
in O
the O
differential O
diagnosis O
, O
and O
compare O
clinico O
- O
pathological O
features O
between O
medullary O
and O
poorly O
differentiated O
adenocarcinoma O
NOS O
. O
Methods O
and O
results O
Histology O
slides O
from O
302 O
colorectal O
cancer O
resections O
originally O
reported O
as O
poorly O
differentiated O
adenocarcinoma O
were O
reviewed O
and O
cases O
fulfilling O
World O
Health O
Organisation O
( O
WHO O
) O
criteria O
for O
medullary O
carcinoma O
identified O
. O
The O
original O
pathology O
report O
was O
examined O
for O
any O
mention O
of O
medullary O
phenotype O
, O
consideration O
of O
neuroendocrine O
differentiation O
or O
consideration O
of O
metastasis O
from O
another O
site O
. O
Clinico O
- O
pathological O
features O
were O
compared O
to O
poorly O
differentiated O
adenocarcinoma O
NOS O
. O
Only O
one O
- O
third O
of O
medullary O
carcinomas O
were O
correctly O
identified O
between O
1997 O
and O
2018 O
. O
The O
other O
two O
- O
thirds O
were O
reported O
as O
poorly O
differentiated O
adenocarcinoma O
NOS O
. O
The O
possibility O
of O
an O
extracolonic O
origin O
or O
neuroendocrine O
carcinoma O
was O
considered O
in O
21 B-STAT
and O
27 O
% O
of O
reports O
. O
Most O
medullary O
carcinomas O
exhibited O
mismatch O
repair O
deficiency O
, O
were O
located O
in O
ascending O
colon O
and O
caecum O
and O
had O
a O
lower O
rate O
of O
vascular O
channel O
invasion O
and O
lymph O
node O
metastasis O
compared O
to O
poorly O
differentiated O
adenocarcinoma O
. O
Conclusions O
Medullary O
carcinoma O
of O
the O
colon O
is O
often O
mistaken O
for O
poorly O
differentiated O
adenocarcinoma O
NOS O
and O
occasionally O
for O
neuroendocrine O
or O
metastatic O
carcinoma O
. O
Greater O
familiarity O
with O
morphological O
criteria O
and O
use O
of O
mismatch O
repair O
protein O
staining O
should O
improve O
diagnosis O
. O
Sweden B-LOC
has O
one O
neonatal O
screening O
laboratory O
, O
receiving O
115 O
to O
120 O
thousand B-STAT
samples I-STAT
per I-STAT
year I-STAT
. O
Among O
the O
one O
million O
babies O
screened O
by O
tandem O
mass O
spectrometry O
from O
November O
2010 O
until O
July O
2019 O
, O
a O
total O
of O
665 O
babies O
were O
recalled O
and O
311 O
verified O
as O
having O
one O
of O
the O
diseases O
screened O
for O
with O
this O
methodology O
, O
giving O
a O
positive O
predictive O
value O
( O
PPV O
) O
of O
47 O
% O
and O
an O
incidence B-EPI
of O
1:3200 O
. O
The O
PPV O
was O
high O
( O
41 O
% O
) O
already O
in O
the O
first O
year O
after O
start O
of O
screening O
, O
thanks O
to O
the O
availability O
of O
the O
collaborative O
project O
Region O
4 O
Stork O
database O
. O
The O
PPV O
is O
presently O
58 B-STAT
% I-STAT
. O
This O
improvement O
was O
achieved O
by O
the O
implementation O
of O
second O
- O
tier O
analyses O
in O
the O
screening O
for O
methylmalonic O
aciduria O
, O
propionic O
aciduria O
, O
isovaleric O
aciduria O
, O
and O
homocystinuria O
, O
and O
the O
employment O
of O
various O
post O
analytical O
tools O
of O
the O
Region O
4 O
Stork O
, O
and O
its O
successor O
the O
collaborative O
laboratory O
integrated O
reports O
. O
Aims O
To O
review O
and O
present O
the O
current O
knowledge O
of O
incidence B-EPI
, O
signs O
and O
symptoms O
, O
diagnosis O
and O
treatment O
of O
the O
occipital O
encephalocele O
. O
Background O
Encephalocele O
( O
E O
) O
is O
a O
defect O
of O
the O
neural O
tube O
that O
refers O
to O
congenital O
malformations O
featured O
by O
skull O
defect O
and O
dura O
with O
extracranial O
spread O
of O
intracranial O
structures O
. O
Occipital O
encephalocele O
( O
OE O
) O
are O
the O
most O
common O
form O
of O
this O
congenital O
disorder O
and O
are O
manifested O
as O
a O
swelling O
of O
different O
sizes O
over O
the O
occipital O
bone O
in O
the O
midline O
. O
Proper O
diagnosis O
and O
treatment O
is O
highly O
important O
in O
the O
management O
of O
this O
congenital O
malformation O
of O
brain O
. O
Objective O
To O
review O
and O
present O
the O
current O
knowledge O
of O
incidence B-EPI
, O
signs O
and O
symptoms O
, O
diagnosis O
and O
treatment O
of O
the O
occipital O
encephalocele O
. O
Methods O
We O
conducted O
a O
search O
of O
case O
reports O
or O
case O
- O
series O
of O
patients O
by O
the O
use O
of O
electronic O
databases O
: O
Pub O
Med O
, O
Medline O
, O
Index O
Medicus O
, O
Scorpus B-LOC
. O
The O
key O
words O
were O
: O
encephalocele O
, O
occipital O
encephalocele O
, O
neural O
tube O
defect O
, O
congenital O
malformation O
. O
The O
search O
was O
updated O
to O
December O
31 O
, O
2018 O
. O
Papers O
published O
in O
English O
were O
the O
only O
source O
of O
information O
. O
Results O
Occipital O
encephalocelle O
are O
more O
frequent O
in O
females O
than O
in O
males O
. O
The O
incidence B-EPI
is O
between O
1 B-STAT
in I-STAT
3000 I-STAT
to O
1 O
in O
10,000 O
live O
births O
; O
approximately O
90 O
% O
of O
them O
involve O
the O
midline O
. O
Magnetic O
resonance O
imaging O
is O
the O
method O
of O
choice O
in O
diagnosis O
and O
surgery O
is O
the O
best O
option O
for O
the O
treatment O
of O
OE O
. O
Overall O
morbidity O
and O
mortality O
is O
still O
high O
in O
spite O
of O
advenced O
surgical O
management O
, O
but O
have O
been O
significantly O
improved O
in O
recent O
years O
thanks O
to O
sophisticated O
highresolution O
imaging O
, O
adequate O
and O
proper O
surgical O
treatment O
and O
decent O
post O
- O
operative O
care O
. O
Conclusion O
Occipital O
encephalocele O
is O
the O
most O
common O
form O
of O
encephalocele O
. O
The O
diagnosis O
is O
mostly O
based O
by O
the O
use O
of O
neuroimaging O
techniques O
. O
Operation O
is O
the O
best O
option O
for O
treatment O
. O
Overall O
morbidity O
and O
mortality O
is O
still O
high O
, O
but O
have O
been O
significantly O
improved O
in O
recent O
years O
thanks O
to O
sophisticated O
high O
- O
resolution O
imaging O
, O
adequate O
and O
proper O
surgical O
treatment O
and O
decent O
post O
- O
operative O
care O
. O
This O
article O
reports O
the O
intent O
to O
receive O
a O
SARS O
- O
COV-2 O
vaccine O
, O
its O
predictors O
and O
willingness O
to O
pay O
in O
Bangladesh B-LOC
. O
We O
carried O
out O
an O
online O
cross O
- O
sectional O
survey O
of O
697 O
adults O
from O
the O
general O
population O
of O
Bangladesh B-LOC
in O
January O
2021 O
. O
A O
structured O
questionnaire O
was O
used O
to O
assess O
vaccination O
intent O
. O
The O
questionnaire O
included O
sociodemographic O
variables O
and O
health O
belief O
model O
constructs O
which O
may O
predict O
vaccination O
intent O
. O
Among O
the O
participants O
, O
26 O
% O
demonstrated O
a O
definite O
intent O
, O
43 O
% O
probable O
intent O
, O
24 O
% O
probable O
negative O
, O
and O
7 O
% O
a O
definite O
negative O
intention O
. O
Multivariable O
logistic O
regression O
analyses O
suggest O
an O
association O
between O
definite O
intent O
and O
previous O
COVID-19 O
infection O
( O
OR O
: O
2.86 O
; O
95 O
% O
CI O
: O
1.71 O
- O
4.78 O
) O
, O
perceiving O
COVID-19 O
as O
serious O
( O
OR O
: O
1.93 O
; O
1.04 O
- O
3.59 O
) O
, O
the O
belief O
that O
vaccination O
would O
make O
them O
feel O
less O
worried O
about O
catching O
COVID-19 O
( O
OR O
: O
4.42 O
; O
2.25 O
- O
8.68 O
) O
, O
and O
concerns O
about O
vaccine O
affordability O
( O
OR O
: O
1.51 O
; O
1.01 O
- O
2.25 O
) O
. O
Individuals O
afraid O
of O
the O
side O
effects O
( O
OR O
: O
0.34 O
; O
0.21 O
- O
0.53 O
) O
and O
those O
who O
would O
take O
the O
vaccine O
if O
the O
vaccine O
were O
taken O
by O
many O
others O
( O
OR O
: O
0.44 O
; O
0.29 O
- O
0.67 O
) O
are O
less O
likely O
to O
have O
a O
definite O
intent O
. O
A O
definite O
negative O
intent O
is O
associated O
with O
the O
concern O
that O
the O
vaccine O
may O
not O
be O
halal O
( O
OR O
: O
2.03 O
; O
1.04 O
- O
3.96 O
) O
. O
Furthermore O
, O
68.4 O
% O
are O
willing O
to O
pay O
for O
the O
vaccine O
. O
The O
median O
amount O
that O
they O
are O
willing O
to O
pay O
is O
USD O
7.08 O
. O
The O
study O
findings O
reveal O
that O
the O
definite O
intent O
to O
receive O
the O
SARS O
- O
CoV-2 O
vaccination O
among O
the O
general O
population O
varies O
depending O
on O
their O
COVID-19 O
- O
related O
health O
beliefs O
and O
no O
significant O
association O
was O
found O
with O
sociodemographic O
variables O
. O
Overlapping O
syndromes O
such O
as O
Noonan O
, O
Cardio O
- O
Facio O
- O
Cutaneous O
, O
Noonan O
syndrome O
( O
NS O
) O
with O
multiple O
lentigines O
and O
Costello O
syndromes O
are O
genetically O
heterogeneous O
conditions O
sharing O
a O
dysregulation O
of O
the O
RAS O
/ O
mitogen O
- O
activated O
protein O
kinase O
( O
MAPK O
) O
pathway O
and O
are O
known O
collectively O
as O
the O
RASopathies O
. O
PTPN11 O
was O
the O
first O
disease O
- O
causing O
gene O
identified O
in O
NS O
and O
remains O
the O
more O
prevalent B-EPI
. O
We O
report O
seven O
patients O
from O
three O
families O
presenting O
heterozygous O
missense O
variants O
in O
PTPN11 O
probably O
responsible O
for O
a O
disease O
phenotype O
distinct O
from O
the O
classical O
Noonan O
syndrome O
. O
The O
clinical O
presentation O
and O
common O
features O
of O
these O
seven O
cases O
overlap O
with O
the O
SHORT O
syndrome O
. O
The O
latter O
is O
the O
consequence O
of O
PI3K B-LOC
/ O
AKT O
signaling O
deregulation O
with O
the O
predominant O
disease O
- O
causing O
gene O
being O
PIK3R1 O
. O
Our O
data O
suggest O
that O
the O
phenotypic O
spectrum O
associated O
with O
pathogenic O
variants O
of O
PTPN11 O
could O
be O
wider O
than O
previously O
described O
, O
and O
this O
could O
be O
due O
to O
the O
dual O
activity O
of O
SHP2 O
( O
ie O
, O
PTPN11 O
gene O
product O
) O
on O
the O
RAS O
/ O
MAPK O
and O
PI3K B-LOC
/ O
AKT O
signaling O
. O
Background O
Consanguineous O
marriages O
are O
common O
in O
the B-LOC
Middle I-LOC
East I-LOC
including O
the O
Gulf B-LOC
countries O
. O
The O
rate O
of O
consanguinity O
in O
Qatar B-LOC
is O
approximately O
54 O
% O
, O
which O
are O
mainly O
first O
cousins O
' O
marriages O
. O
Previous O
studies O
showed O
that O
consanguinity O
increases O
the O
prevalence B-EPI
of O
birth O
defects O
and O
other O
genetic O
disorders O
. O
Thus O
, O
we O
studied O
the O
effects O
of O
consanguinity O
in O
a O
cohort O
of O
subjects O
with O
certain O
genetic O
disorders O
in O
Qatar B-LOC
. O
Methods O
This O
cross O
- O
sectional O
study O
was O
conducted O
at O
two O
centers O
in O
Qatar B-LOC
( O
Hamad O
Medical O
Corporation O
O
HMC O
O
and O
Shafallah O
O
SC O
O
) O
including O
599 O
Qatari O
families O
with O
certain O
types O
of O
genetic O
and O
nongenetic O
anomalies O
. O
Results O
Consanguineous O
marriages O
were O
seen O
in O
397 O
of O
599 B-STAT
( O
66.2 O
% O
) O
Qatari O
families O
and O
first O
cousin O
group O
counts O
for O
65 O
% O
in O
Qatari O
population O
. O
In O
the O
total O
cohort O
and O
at O
HMC O
, O
all O
consanguineous O
marriages O
had O
a O
significantly O
higher O
risk O
of O
Autosomal O
Recessive O
disorders O
than O
nonconsanguineous O
marriages O
( O
total O
cohort O
: O
odds O
ratio O
( O
OR O
) O
= O
1.72 O
; O
95 O
% O
CI O
: O
1.10 O
, O
2.71 O
; O
p O
= O
.02 O
; O
HMC O
: O
OR O
= O
2.98 O
; O
95 O
% O
CI O
: O
1.37 O
, O
6.09 O
; O
p O
= O
.005 O
) O
. O
On O
the O
other O
hand O
, O
at O
HMC O
, O
nonconsanguinity O
was O
significantly O
related O
to O
chromosomal O
abnormality O
( O
OR O
= O
6.36 O
; O
95 O
% O
CI O
: O
1.13 O
, O
35.85 O
; O
p O
= O
.036 O
) O
. O
Conclusion O
Our O
data O
suggest O
a O
significant O
role O
of O
parental O
consanguinity O
in O
increasing O
the O
prevalence B-EPI
of O
genetic O
disorders O
; O
mainly O
Autosomal O
Recessive O
disorders O
. O
Chromosomal O
abnormality O
disorders O
were O
significantly O
higher O
among O
nonconsanguineous O
marriages O
. O
These O
results O
help O
better O
inform O
policy O
makers O
on O
social O
, O
educational O
, O
and O
public O
health O
initiatives O
that O
might O
mitigate O
the O
impact O
of O
genetic O
disease O
in O
the O
Qatari O
society O
. O
Loss O
- O
of O
- O
function O
( O
LoF O
) O
mutations O
in O
KCNQ1 B-LOC
, O
encoding O
the O
voltage O
- O
gated O
K O
+ O
channel O
K O
v O
7.1 O
, O
lead O
to O
long O
QT O
syndrome O
1 O
( O
LQT1 O
) O
. O
LQT1 O
patients O
also O
present O
with O
post O
- O
prandial O
hyperinsulinemia O
and O
hypoglycaemia O
. O
In O
contrast O
, O
KCNQ1 O
polymorphisms O
are O
associated O
with O
diabetes O
, O
and O
LQTS O
patients O
have O
a O
higher O
prevalence B-EPI
of O
diabetes O
. O
We O
developed O
a O
mouse O
model O
with O
a O
LoF O
Kcnq1 O
mutation O
using O
CRISPR O
- O
Cas9 O
and O
hypothesized O
that O
this O
mouse O
model O
would O
display O
QT O
prolongation O
, O
increased O
glucose O
- O
stimulated O
insulin O
secretion O
and O
allow O
for O
interrogation O
of O
K O
v O
7.1 O
function O
in O
islets O
. O
Mice O
were O
characterized O
by O
electrocardiography O
and O
oral O
glucose O
tolerance O
tests O
. O
Ex O
vivo O
, O
islet O
glucose O
- O
induced O
insulin O
release O
was O
measured O
, O
and O
beta O
- O
cell O
area O
quantified O
by O
immunohistochemistry O
. O
Homozygous O
mice O
had O
QT O
prolongation O
. O
Ex O
vivo O
, O
glucose O
- O
stimulated O
insulin O
release O
was O
increased O
in O
islets O
from O
homozygous O
mice O
at O
12 O
- O
14 O
weeks O
, O
while O
beta O
- O
cell O
area O
was O
reduced O
. O
Non O
- O
fasting O
blood O
glucose O
levels O
were O
decreased O
at O
this O
age O
. O
In O
follow O
- O
up O
studies O
8 O
- O
10 O
weeks O
later O
, O
beta O
- O
cell O
area O
was O
similar O
in O
all O
groups O
, O
while O
glucose O
- O
stimulated O
insulin O
secretion O
was O
now O
reduced O
in O
islets O
from O
hetero- O
and O
homozygous O
mice O
. O
Non O
- O
fasting O
blood O
glucose O
levels O
had O
normalized O
. O
These O
data O
suggest O
that O
K O
v O
7.1 O
dysfunction O
is O
involved O
in O
a O
transition O
from O
hyper- O
to O
hyposecretion O
of O
insulin O
, O
potentially O
explaining O
the O
association O
with O
both O
hypoglycemia O
and O
hyperglycemia O
in O
LQT1 O
patients O
. O
Girls O
with O
Fragile O
- O
X O
- O
Syndrome O
( O
FXS O
) O
present O
high O
levels O
of O
social O
anxiety O
, O
social O
avoidance O
, O
extreme O
shyness O
, O
tendency O
to O
social O
isolation O
, O
poor O
eye O
contact O
, O
learning O
difficulties O
, O
and O
depression O
. O
The O
aims O
of O
the O
present O
study O
, O
which O
is O
based O
on O
a O
group O
of O
young O
females O
with O
FXS O
are O
: O
1 O
) O
to O
analyze O
the O
possible O
associations O
between O
emotion O
recognition O
, O
theory O
of O
mind O
, O
and O
social O
anxiety O
, O
and O
adaptive O
behavior O
, O
and O
emotional O
state O
; O
2 O
) O
to O
study O
the O
relationship O
between O
intelligence O
quotient O
( O
IQ O
) O
and O
adaptive O
behavior O
; O
and O
3 O
) O
to O
assess O
whether O
social O
anxiety O
is O
more O
prevalent B-EPI
in O
girls O
with O
FXS O
. O
The O
study O
has O
40 O
female O
participants O
aged O
between O
7 O
and O
16 O
years O
( O
26 O
positive O
full O
mutation O
FXS O
and O
14 O
as O
a O
control O
group O
) O
. O
A O
neuropsychological O
assessment O
was O
conducted O
using O
the O
following O
tests O
: O
WISC O
- O
V O
, O
NEPSY O
- O
II O
, O
SENA O
, O
ADHD O
Rating O
Scale O
, O
BAS O
, O
and O
ABAS O
- O
II O
. O
In O
comparison O
with O
the O
control O
group O
, O
the O
group O
with O
FXS O
presented O
a O
greater O
association O
between O
IQ O
and O
self O
- O
direction O
ability O
, O
and O
between O
emotion O
recognition O
and O
leadership O
. O
The O
FXS O
group O
presented O
higher O
levels O
of O
social O
anxiety O
and O
shyness O
. O
In O
the O
group O
of O
girls O
with O
FXS O
, O
IQ O
may O
have O
prognostic O
value O
for O
both O
self O
- O
direction O
ability O
and O
social O
adaptation O
level O
. O
Purpose O
We O
observed O
four O
individuals O
in O
two O
unrelated O
but O
consanguineous O
families O
from O
Portugal B-LOC
and O
Brazil B-LOC
affected O
by O
early O
- O
onset O
retinal O
degeneration O
, O
sensorineural O
hearing O
loss O
, O
microcephaly O
, O
intellectual O
disability O
, O
and O
skeletal O
dysplasia O
with O
scoliosis O
and O
short O
stature O
. O
The O
phenotype O
precisely O
matched O
that O
of O
an O
individual O
of O
Azorean O
descent O
published O
in O
1986 O
by O
Liberfarb B-LOC
and O
coworkers O
. O
Methods O
Patients O
underwent O
specialized O
clinical O
examinations O
( O
including O
ophthalmological O
, O
audiological O
, O
orthopedic O
, O
radiological O
, O
and O
developmental O
assessment O
) O
. O
Exome O
and O
targeted O
sequencing O
was O
performed O
on O
selected O
individuals O
. O
Minigene O
constructs O
were O
assessed O
by O
quantitative O
polymerase O
chain O
reaction O
( O
qPCR O
) O
and O
Sanger O
sequencing O
. O
Results O
Affected O
individuals O
shared O
a O
3.36 O
- O
Mb O
region O
of O
autozygosity O
on O
chromosome O
22q12.2 O
, O
including O
a O
10 O
- O
bp O
deletion O
( O
NM_014338.3 O
: O
c.904 O
- O
12_904 O
- O
3delCTATCACCAC O
) O
, O
immediately O
upstream O
of O
the O
last O
exon O
of O
the O
PISD O
( O
phosphatidylserine O
decarboxylase O
) O
gene O
. O
Sequencing O
of O
PISD O
from O
paraffin O
- O
embedded O
tissue O
from O
the O
1986 O
case O
revealed O
the O
identical O
homozygous O
variant O
. O
In O
HEK293 B-LOC
T O
cells O
, O
this O
variant O
led O
to O
aberrant O
splicing O
of O
PISD O
transcripts O
. O
Conclusion O
We O
have O
identified O
the O
genetic O
etiology O
of O
the O
Liberfarb B-LOC
syndrome O
, O
affecting O
brain O
, O
eye O
, O
ear O
, O
bone O
, O
and O
connective O
tissue O
. O
Our O
work O
documents O
the O
migration O
of O
a O
rare O
Portuguese O
founder O
variant O
to O
two O
continents O
and O
highlights O
the O
link O
between O
phospholipid O
metabolism O
and O
bone O
formation O
, O
sensory O
defects O
, O
and O
cerebral O
development O
, O
while O
raising O
the O
possibility O
of O
therapeutic O
phospholipid O
replacement O
. O
Hemimelia O
is O
a O
rare O
anomaly O
affecting O
the O
distal O
long O
bones O
of O
extremities O
, O
with O
an O
occurrence B-EPI
of O
1 B-STAT
- I-STAT
20 I-STAT
cases I-STAT
per I-STAT
million I-STAT
of I-STAT
live I-STAT
births I-STAT
depending O
on O
the O
affected O
bone O
. O
Hemimelia B-LOC
can O
be O
an O
isolated O
defect O
or O
be O
part O
of O
complex O
syndromes O
that O
affect O
extra O
skeletal O
structures O
. O
Prenatal O
detection O
by O
routine O
ultrasound O
imaging O
is O
difficult O
and O
yields O
low O
detection O
rates O
. O
The O
prenatal O
diagnosis O
of O
hemimelia O
should O
prompt O
a O
complete O
and O
detailed O
study O
of O
the O
fetal O
anatomy O
, O
since O
it O
can O
be O
associated O
with O
defects O
in O
other O
structures O
and O
systems O
, O
as O
the O
reported O
in O
this O
case O
. O
The O
prognosis O
depends O
upon O
the O
associated O
anomalies O
. O
Objective O
To O
evaluate O
the O
safety O
and O
efficacy O
of O
radiofrequency O
ablation O
( O
RFA O
) O
for O
metastatic O
lymph O
nodes O
( O
LNs O
) O
in O
children O
and O
adolescents O
with O
papillary O
Thyroid O
Carcinoma O
( O
PTC O
) O
. O
Materials O
and O
methods O
From O
December O
2014 O
to O
March O
2018 O
, O
10 O
metastatic O
LNs(mean B-LOC
volume O
0.30 O
± O
0.38 O
ml O
, O
range O
0.06 O
- O
1.23ml O
) O
in O
5 O
children O
and O
adolescents O
( O
3 O
females O
, O
2 O
males O
; O
mean O
age O
15.60 O
± O
2.97 O
years O
, O
range O
12 O
- O
19 O
years O
) O
with O
PTC O
treated O
by O
RFA O
were O
evaluated O
in O
this O
study O
. O
The O
mean O
number O
of O
surgical O
procedures O
performed O
before O
RFA O
was O
1.2 O
( O
range O
1 B-STAT
- I-STAT
2 I-STAT
) O
and O
the O
mean O
number O
of O
treated O
metastatic O
LNs O
per O
patient O
was O
2 O
( O
rang O
1 B-STAT
- I-STAT
3 I-STAT
) O
. O
RFA O
was O
performed O
with O
an O
18 O
- O
gauge O
bipolar O
RF O
applicator O
under O
local O
anesthesia O
. O
Follow O
- O
up O
consisted O
of O
US B-LOC
and O
serum O
thyroglobulin O
( O
Tg O
) O
level O
at O
1 B-STAT
, I-STAT
3 I-STAT
, O
6 O
, O
12 O
months O
and O
every O
12 O
months O
thereafter O
. O
Results O
All O
the O
patients O
were O
well O
tolerant O
to O
RFA O
procedure O
and O
no O
procedure O
- O
related O
complications O
occurred O
. O
During O
a O
mean O
follow O
- O
up O
time O
of O
52.00 O
± O
21.44 O
months O
, O
the O
initial O
volume O
of O
LNs O
was O
0.30 O
± O
0.38 O
ml O
, O
which O
significantly O
decreased O
to O
0.01 O
± O
0.03 O
ml O
( O
P O
= O
0.005 O
) O
with O
a O
mean O
VRR O
of O
99.28 O
± O
2.27 O
% O
. O
A O
total O
of O
9 O
metastatic O
LNs O
( O
90.00 O
% O
) O
completely O
disappeared O
. O
After O
RFA O
, O
2 O
patients O
developed O
newly O
metastases O
. O
One O
patient O
had O
additional O
RFA O
. O
The O
other O
one O
with O
multiple O
LN O
metastases O
underwent O
total O
thyroidectomy O
with O
central O
neck O
dissection O
. O
Conclusion O
As O
a O
less O
invasive O
and O
effective O
technique O
, O
RFA O
may O
provide O
another O
alternative O
to O
the O
existing O
therapeutic O
modalities O
for O
cervical O
metastatic O
LNs O
in O
children O
and O
adolescents O
with O
PTC O
. O
Background O
The O
prevalence B-EPI
of O
Multiple O
Sclerosis O
( O
MS O
) O
has O
been O
increasing O
worldwide B-LOC
and O
the O
highest O
prevalence B-EPI
ratio O
among O
Asian O
countries O
was O
reported O
in O
Iran B-LOC
. O
This O
study O
aims O
to O
estimate O
the O
increase O
in O
MS O
occurrence B-EPI
during O
more O
than O
three O
decades O
in O
Tehran B-LOC
and O
forecast O
the O
future O
condition O
of O
the O
disease O
using O
time O
series O
approaches O
for O
the O
next O
ten O
years O
. O
Methods O
The O
cross O
- O
sectional O
study O
was O
conducted O
from O
1999 O
to O
2019 O
based O
on O
records O
of O
MS O
cases O
from O
Iranian O
MS O
Society O
( O
IMSS O
) O
registry O
system O
. O
The O
prevalence B-EPI
was O
estimated O
using O
population O
data O
presented O
by O
the O
Statistical O
Centre O
of O
Iran O
. O
Through O
Bayesian O
Structural O
Time O
Series O
( O
BSTS O
) O
model O
, O
we O
want O
to O
predict O
the O
prevalence B-EPI
of O
familial O
and O
sporadic O
MS O
in O
the O
next O
ten O
years O
. O
. O
Results O
Among O
22,421 O
cases O
with O
MS O
, O
16,831 O
( O
75.1 O
% O
) O
were O
female O
and O
5589 O
( O
24.9 O
% O
) O
were O
male O
. O
Female O
to O
male O
ratio O
was O
3.0:1 O
and O
the O
number O
of O
familial O
MS O
cases O
were O
2982 O
( O
13.3 O
% O
) O
of O
subjects O
. O
Female O
gender O
was O
less O
responsible O
for O
higher O
rate O
of O
MS O
in O
familial O
definition O
( O
beta O
= O
0.020 O
) O
in O
comparison O
to O
sporadic O
cases O
( O
beta O
= O
0.034 O
) O
. O
Forecasting O
by O
BSTS O
revealed O
an O
increase O
in O
MS O
prevalence B-EPI
for O
the O
next O
ten O
years O
so O
that O
the O
prevalence B-EPI
rate O
for O
total O
, O
familial O
and O
sporadic O
MS B-LOC
respectively O
begins O
with O
189.50 O
( O
183.94 O
- O
195.14 O
) O
, O
25.69 O
( O
24.97 O
- O
26.45 O
) O
and O
163.74(159.06 O
- O
168.57 O
) O
in O
2020 O
and O
ends O
with O
220.84 O
( O
171.48 O
- O
266.92 O
) O
, O
30.79 O
( O
24.16 O
- O
37.15 O
) O
, O
and O
189.33(146.97 O
- O
230.19 O
) O
in O
2029 O
. O
Conclusions O
According O
to O
the O
findings O
, O
MS O
prevalence B-EPI
increased O
during O
three O
decades O
and O
it O
will O
increase O
over O
the O
next O
ten O
years O
. O
Tehran B-LOC
province O
is O
one O
of O
the O
regions O
with O
highest O
MS O
prevalence B-EPI
in O
Asia B-LOC
. O
The O
results O
of O
present O
study O
indicated O
that O
females O
are O
at O
higher O
risk O
for O
MS O
than O
males O
in O
both O
sporadic O
and O
familial O
MS O
. O
Background O
and O
aim O
This O
study O
aimed O
to O
describe O
the O
clinical O
, O
genetic O
, O
and O
epidemiological O
features O
of O
Charcot O
- O
Marie O
- O
Tooth O
disease O
( O
CMT O
) O
in O
Brazilian O
patients O
from O
a O
tertiary O
center O
, O
and O
to O
compare O
our O
data O
with O
previously O
published O
findings O
. O
Methods O
This O
retrospective O
observational O
study O
conducted O
between O
February O
2015 O
and O
July O
2020 O
evaluated O
503 O
patients O
( O
94 O
families O
and O
192 O
unrelated O
individuals O
) O
, O
diagnosed O
with O
CMT O
. O
Clinical O
and O
neurophysiological O
data O
were O
obtained O
from O
electronic O
medical O
records O
and O
blood O
samples O
were O
used O
for O
genetic O
analyses O
. O
Multiplex O
ligation O
- O
dependent O
probe O
amplification O
was O
used O
to O
assess O
duplications O
/ O
deletions O
in O
PMP22 O
. O
Sanger O
sequencing O
of O
GJB1 O
was O
performed O
in O
cases O
of O
suspected O
demyelinating O
CMT O
. O
Targeted O
gene O
panel O
sequencing O
was O
used O
for O
the O
remaining O
negative O
demyelinating O
cases O
and O
all O
axonal O
CMT O
cases O
. O
Results O
The O
first O
decade O
of O
life O
was O
the O
most O
common O
period O
of O
disease O
onset O
. O
In O
all O
, O
353 O
patients O
had O
demyelinating O
CMT O
, O
39 O
had O
intermediate O
CMT O
, O
and O
111 O
had O
axonal O
CMT O
. O
Pathogenic O
or O
likely O
pathogenic O
variants O
were O
identified O
in O
197 O
index O
cases O
. O
The O
most O
common O
causative O
genes O
among O
probands O
were O
PMP22 O
( O
duplication O
) O
( O
n=116 O
, O
58.88 O
% O
) O
, O
GJB1 O
( O
n=23 O
, O
11.67 O
% O
) O
, O
MFN2 O
( O
n=12 O
, O
6.09 O
% O
) O
, O
GDAP1 O
( O
n=7 O
, O
3.55 O
% O
) O
, O
MPZ O
( O
n=6 O
, O
3.05 O
% O
) O
, O
PMP22 O
( O
point O
mutation O
) O
( O
n=6 O
, O
3.05 O
% O
) O
, O
NEFL O
( O
n=3 O
, O
1.52 O
% O
) O
, O
SBF2 O
( O
n=3 O
, O
1.52 O
% O
) O
, O
and O
SH3TC2 O
( O
n=3 O
, O
1.52 O
% O
) O
. O
Other O
identified O
variants O
were O
≤1 O
% O
of O
index O
cases O
. O
Interpretation O
This O
study O
provides O
further O
data O
on O
the O
frequency O
of O
CMT O
subtypes O
in O
a O
Brazilian O
clinical O
- O
based O
population O
and O
highlights O
the O
importance O
of O
rarer O
and O
previously O
undiagnosed O
variants O
in O
clinical O
practice O
. O
This O
article O
is O
protected O
by O
copyright O
. O
All O
rights O
reserved O
. O
Aim O
To O
assess O
a O
total O
population O
of O
school O
- O
age O
children O
with O
cerebral O
palsy O
( O
CP O
) O
for O
autism O
and O
attention O
- O
deficit O
/ O
hyperactivity O
disorder O
( O
ADHD O
) O
with O
a O
view O
to O
determining O
their O
prevalence B-EPI
and O
to O
relate O
findings O
to O
motor O
function O
, O
intellectual O
disability O
, O
and O
other O
associated O
impairments O
. O
Method O
Of O
264 O
children O
, O
born O
between O
1999 O
and O
2006 O
, O
from O
the O
CP O
register O
of O
western O
Sweden B-LOC
, O
200 O
children O
( O
109 O
males O
, O
91 O
females O
, O
median O
age O
at O
assessment O
14y O
, O
range O
7 O
- O
18y O
) O
completed O
comprehensive O
screening O
and O
further O
neuropsychiatric O
clinical O
assessments O
. O
Results O
Ninety O
children O
( O
45 O
% O
) O
were O
diagnosed O
with O
autism O
, O
ADHD O
, O
or O
both O
, O
59 B-STAT
( O
30 O
% O
) O
were O
diagnosed O
with O
autism O
, O
and O
60 B-STAT
( O
30 O
% O
) O
were O
diagnosed O
with O
ADHD O
. O
Intellectual O
disability O
was O
present O
in O
51 B-STAT
% I-STAT
. O
Two O
- O
thirds O
had O
autism O
, O
ADHD O
, O
and/or O
intellectual O
disability O
. O
In O
regression O
models O
, O
autism O
was O
mainly O
predicted O
by O
intellectual O
disability O
( O
odds O
ratio O
[ O
OR]=4.1 O
) O
and O
ADHD O
( O
OR=3.2 O
) O
, O
and O
ADHD O
was O
predicted O
by O
intellectual O
disability O
( O
OR=2.3 O
) O
and O
autism O
( O
OR=3.0 O
) O
. O
Autism O
was O
more O
common O
in O
children O
born O
preterm O
( O
OR=2.0 O
) O
. O
Gross O
motor O
function O
was O
not O
associated O
with O
autism O
. O
ADHD O
prevalence B-EPI
was O
low O
in O
children O
with O
severe O
motor O
impairment O
, O
possibly O
due O
to O
diagnostic O
limitations O
. O
Interpretation O
Autism O
and O
ADHD O
were O
common O
in O
this O
population O
of O
children O
with O
CP O
and O
were O
mainlyindependent O
of O
motor O
severity O
and O
CP O
type O
. O
The O
strongest O
predictor O
of O
autism O
/ O
ADHD O
was O
intellectual O
disability O
. O
Assessment O
for O
autism O
and O
ADHD O
is O
warranted O
as O
part O
of O
the O
evaluation O
in O
CP O
. O
What O
this O
paper O
adds O
Forty B-STAT
- O
five O
percent O
of O
the O
children O
with O
cerebral O
palsy O
also O
had O
autism O
, O
attention O
- O
deficit O
/ O
hyperactivity O
disorder O
( O
ADHD O
) O
, O
or O
both O
. O
Autism O
and O
ADHD O
were O
predicted O
mainly O
by O
intellectual O
disability O
. O
Established O
diagnostic O
instruments O
worked O
well O
for O
all O
but O
the O
most O
disabled O
group O
of O
children O
. O
Background O
The O
VACTERL O
association O
( O
VACTERL O
) O
is O
the O
nonrandom O
occurrence B-EPI
of O
at O
least O
three O
of O
these O
congenital O
anomalies O
: O
vertebral O
, O
anal O
, O
cardiac O
, O
tracheoesophageal O
, O
renal O
, O
and O
limb O
anomalies O
. O
Despite O
suggestions O
for O
involvement O
of O
several O
genes O
and O
nongenetic O
risk O
factors O
from O
small O
studies O
, O
the O
etiology O
of O
VACTERL O
remains O
largely O
unknown O
. O
Objective O
To O
identify O
maternal O
risk O
factors O
for O
VACTERL O
in O
offspring O
in O
a O
large O
European O
study O
. O
Methods O
A O
case O
- O
control O
study O
was O
performed O
using O
data O
from O
28 O
EUROCAT O
registries O
over O
the O
period O
1997 O
- O
2015 O
with O
case O
and O
control O
ascertainment O
through O
hospital O
records O
, O
birth O
and O
death O
certificates O
, O
questionnaires O
, O
and/or O
postmortem O
examinations O
. O
Cases O
were O
diagnosed O
with O
VACTERL O
, O
while O
controls O
had O
a O
genetic O
syndrome O
and/or O
chromosomal O
abnormality O
. O
Data O
collected O
included O
type O
of O
birth O
defect O
and O
maternal O
characteristics O
, O
such O
as O
age O
, O
use O
of O
assisted O
reproductive O
techniques O
( O
ART O
) O
, O
and O
chronic O
illnesses O
. O
Multivariable O
logistic O
regression O
analyses O
were O
performed O
to O
estimate O
confounder O
adjusted O
odds O
ratios O
( O
aOR O
) O
with O
95 O
% O
confidence O
intervals O
( O
95 O
% O
CI O
) O
. O
Results O
The O
study O
population O
consisted O
of O
329 O
VACTERL O
cases O
and O
49,724 O
controls O
with O
recognized O
syndromes O
or O
chromosomal O
abnormality O
. O
For O
couples O
who O
conceived O
through O
ART O
, O
we O
found O
an O
increased O
risk O
of O
VACTERL O
( O
aOR O
2.3 B-STAT
[ O
95 O
% O
CI O
1.3 O
, O
3.9 O
] O
) O
in O
offspring O
. O
Pregestational O
diabetes O
( O
aOR O
3.1 O
[ O
95 O
% O
CI O
1.1 O
, O
8.6 O
] O
) O
and O
chronic O
lower O
obstructive O
pulmonary O
diseases O
( O
aOR O
3.9 O
[ O
95 O
% O
CI O
2.2 O
, O
6.7 O
] O
) O
also O
increased O
the O
risk O
of O
having O
a O
child O
with O
VACTERL O
. O
Twin O
pregnancies O
were O
not O
associated O
with O
VACTERL O
( O
aOR O
0.6 O
[ O
95 O
% O
CI O
0.3 O
, O
1.4 O
] O
) O
. O
Conclusion O
We O
identified O
several O
maternal O
risk O
factors O
for O
VACTERL O
in O
offspring O
befitting O
a O
multifactorial O
etiology O
. O
Limb O
deficiency O
disorders O
are O
rare O
, O
etiologically O
heterogeneous O
skeletal O
dysplasias O
that O
occur O
as O
an O
isolated O
anomaly O
or O
as O
a O
part O
of O
a O
syndrome O
. O
The O
term O
limb O
deficiency O
incorporates O
both O
absence O
and O
size O
reduction O
of O
any O
of O
the O
120 O
human O
limb O
bones O
, O
with O
around O
205 O
identified O
abnormalities O
. O
Congenital O
absence O
of O
tibia O
is O
a O
rare O
and O
severe O
lower O
limb O
malformation O
with O
an O
incidence B-EPI
of O
approximately B-STAT
1:1,000,000 I-STAT
live I-STAT
births I-STAT
. O
Absence O
of O
tibia O
with O
ectrodactyly O
( O
lobster O
claw O
deformity O
) O
or O
tibial O
hemimelia O
with O
split O
hand O
/ O
foot O
malformation O
( O
TH O
- O
SHFM O
) O
or O
Gollop O
- O
Wolfgang O
complex O
is O
a O
rarer O
malformation O
with O
highly O
variable O
manifestations O
. O
Background O
Craniosynostosis O
, O
defined O
as O
premature O
fusion O
of O
one O
or O
more O
cranial O
sutures O
, O
affects O
approximately O
1 B-STAT
in I-STAT
every I-STAT
2000 I-STAT
- O
2500 O
live O
births O
. O
Sagittal O
craniosynostosis O
( O
CS O
) O
, O
the O
most O
prevalent B-EPI
form O
of O
isolated O
craniosynostosis O
, O
is O
caused O
by O
interplay O
between O
genetic O
and O
perinatal O
environmental O
insults O
. O
However O
, O
the O
underlying O
details O
remain O
largely O
unknown O
. O
Methods O
The O
proband O
( O
a O
female O
monochorionic O
twin O
diagnosed O
with O
CS O
) O
, O
her O
healthy O
co O
- O
twin O
sister O
and O
parents O
were O
enrolled O
. O
Obstetric O
history O
was O
extracted O
from O
medical O
records O
. O
Genetic O
screening O
was O
performed O
by O
whole O
exome O
sequencing O
( O
WES O
) O
and O
confirmed O
by O
Sanger O
sequencing O
. O
Functional O
annotation O
, O
conservation O
and O
structural O
analysis O
were O
predicted O
in O
public O
database O
. O
Phenotype O
data O
of O
Axin2 O
knockout O
mice O
was O
downloaded O
from O
The O
International O
Mouse O
Phenotyping O
Consortium O
( O
IMPC O
, O
http://www.mousephenotype.org O
) O
. O
Results O
Obstetric O
medical O
records O
showed O
that O
, O
except O
for O
the O
shared O
perinatal O
risk O
factors O
by O
the O
twins O
, O
the O
proband O
suffered O
additional O
persistent O
breech O
presentation O
and O
intrauterine O
growth O
restriction O
. O
We O
identified O
a O
heterozygous O
mutation O
of O
Axin2 O
( O
c.1181 O
G O
> O
A O
, O
p. O
R394H O
, O
rs200899695 O
) O
in O
monochorionic O
twins O
and O
their O
father O
, O
but O
not O
in O
the O
mother O
. O
This O
mutation O
is O
not O
reported O
in O
Asian O
population O
and O
results O
in O
replacement O
of O
Arg O
at O
residue O
394 O
by O
His O
( O
p. O
R394H O
) O
. O
Arg O
394 O
is O
located O
at O
the O
GSK3β O
binding O
domain O
of O
Axin2 O
protein O
, O
which O
is O
highly O
conserved O
across O
species O
. O
The O
mutation O
was O
predicted O
to O
be O
potentially O
deleterious O
by O
in O
silico O
analysis O
. O
Incomplete O
penetrance O
of O
Axin2 O
haploinsufficiency O
was O
found O
in O
female O
mice O
. O
Conclusions O
Axin2 O
( O
c.1181 O
G O
> O
A O
, O
p. O
R394H O
, O
rs200899695 O
) O
mutation O
confers O
susceptibility O
and O
perinatal O
risk O
factors O
trigger O
the O
occurrence B-EPI
of O
sagittal O
craniosynostosis O
. O
Our O
findings O
provide O
a O
new O
evidence O
for O
the O
gene O
- O
environment O
interplay O
in O
understanding O
pathogenesis O
of O
craniosynostosis O
in O
Chinese O
population O
. O
Background O
The O
Global O
Anticoagulant O
Registry O
in O
the O
FIELD O
- O
Atrial O
Fibrillation O
( O
GARFIELD O
- O
AF O
) O
is O
an O
ongoing O
prospective O
noninterventional O
registry O
, O
which O
is O
providing O
important O
information O
on O
the O
baseline O
characteristics O
, O
treatment O
patterns O
, O
and O
1 O
- O
year O
outcomes O
in O
patients O
with O
newly O
diagnosed O
non O
- O
valvular O
atrial O
fibrillation O
( O
NVAF O
) O
. O
This O
report O
describes O
data O
from O
Indian O
patients O
recruited O
in O
this O
registry O
. O
Methods O
and O
results O
A O
total O
of O
52,014 O
patients O
with O
newly O
diagnosed O
AF O
were O
enrolled O
globally O
; O
of O
these O
, O
1388 O
patients O
were O
recruited O
from O
26 O
sites O
within O
India B-LOC
( O
2012 O
- O
2016 O
) O
. O
In O
India B-LOC
, O
the O
mean O
age O
was O
65.8 O
years O
at O
diagnosis O
of O
NVAF O
. O
Hypertension O
was O
the O
most O
prevalent B-EPI
risk O
factor O
for O
AF O
, O
present O
in O
68.5 O
% O
of O
patients O
from O
India B-LOC
and O
in O
76.3 O
% O
of O
patients O
globally O
( O
P O
< O
0.001 O
) O
. O
Diabetes O
and O
coronary O
artery O
disease O
( O
CAD O
) O
were O
prevalent B-EPI
in O
36.2 O
% O
and O
28.1 O
% O
of O
patients O
as O
compared O
with O
global B-LOC
prevalence B-EPI
of O
22.2 O
% O
and O
21.6 O
% O
, O
respectively O
( O
P O
< O
0.001 O
for O
both O
) O
. O
Antiplatelet O
therapy O
was O
the O
most O
common O
antithrombotic O
treatment O
in O
India B-LOC
. O
With O
increasing O
stroke O
risk O
, O
however O
, O
patients O
were O
more O
likely O
to O
receive O
oral O
anticoagulant O
therapy O
[ O
mainly O
vitamin O
K O
antagonist O
( O
VKA O
) O
] O
, O
but O
average O
international O
normalized O
ratio O
( O
INR O
) O
was O
lower O
among O
Indian O
patients O
[ O
median O
INR O
value O
1.6 O
( O
interquartile O
range O
{ O
IQR O
} O
: O
1.3 O
- O
2.3 O
) O
versus O
2.3 O
( O
IQR O
1.8 O
- O
2.8 O
) O
( O
P O
< O
0.001 O
) O
] O
. O
Compared O
with O
other O
countries O
, O
patients O
from O
India B-LOC
had O
markedly O
higher O
rates O
of O
all O
- O
cause O
mortality O
[ O
7.68 B-STAT
per I-STAT
100 I-STAT
person I-STAT
- O
years O
( O
95 O
% O
confidence O
interval O
6.32 O
- O
9.35 O
) O
vs O
4.34 O
( O
4.16 O
- O
4.53 O
) O
, O
P O
< O
0.0001 O
] O
, O
while O
rates O
of O
stroke O
/ O
systemic O
embolism O
and O
major O
bleeding O
were O
lower O
after O
1 B-STAT
year I-STAT
of I-STAT
follow O
- O
up O
. O
Conclusion O
Compared O
to O
previously O
published O
registries O
from O
India B-LOC
, O
the O
GARFIELD O
- O
AF O
registry O
describes O
clinical O
profiles O
and O
outcomes O
in O
Indian O
patients O
with O
AF O
of O
a O
different O
etiology O
. O
The O
registry O
data O
show O
that O
compared O
to O
the O
rest O
of O
the O
world O
, O
Indian O
AF O
patients O
are O
younger O
in O
age O
and O
have O
more O
diabetes O
and O
CAD O
. O
Patients O
with O
a O
higher O
stroke O
risk O
are O
more O
likely O
to O
receive O
anticoagulation O
therapy O
with O
VKA O
but O
are O
underdosed O
compared O
with O
the O
global O
average O
in O
the O
GARFIELD O
- O
AF O
. O
CLINICAL O
TRIAL O
REGISTRATION O
- O
URL O
: O
http://www.clinicaltrials.gov O
. O
Unique O
identifier O
: O
NCT01090362 O
. O
Takotsubo O
cardiomyopathy O
( O
TCM O
) O
, O
also O
known O
as O
broken O
heart O
syndrome O
or O
stress O
- O
induced O
cardiomyopathy O
, O
is O
a O
rare O
condition O
with O
an O
estimated B-EPI
incidence I-EPI
of O
0.02 B-STAT
% I-STAT
of O
all O
hospitalizations O
in O
United B-LOC
States I-LOC
and O
2 O
% O
of O
all O
acute O
coronary O
syndrome O
presentations O
. O
TCM O
predominately O
presents O
as O
a O
transient O
wall O
motion O
abnormality O
of O
the O
left O
ventricular O
apex O
due O
to O
emotional O
or O
physical O
stress O
. O
Cardiac O
rupture O
in O
the O
setting O
of O
TCM O
is O
an O
extremely O
rare O
phenomenon O
with O
limited O
published O
case O
reports O
. O
We O
present O
a O
case O
of O
a O
75 O
- O
year O
- O
old O
female O
who O
had O
cardiac O
rupture O
secondary O
to O
TCM O
and O
performed O
a O
literature O
review O
using O
Ovid O
MEDLINE O
for O
published O
cases O
showing O
this O
association O
. O
After O
the O
literature O
review O
, O
we O
found O
20 O
cases O
showing O
this O
association O
, O
which O
are O
listed O
in O
a O
tabular O
fashion O
. O
Although O
West B-LOC
Nile I-LOC
virus O
( O
WNV O
) O
is O
endemic O
to O
South B-LOC
Africa I-LOC
( O
RSA O
) O
, O
it O
has O
only O
become O
recognized O
as O
a O
significant O
cause O
of O
neurological O
disease O
in O
humans O
and O
horses O
locally O
in O
the O
past O
2 O
decades O
, O
as O
it O
emerged O
globally O
. O
This O
article O
describes O
the O
epidemiological O
and O
clinical O
presentation O
of O
WNV O
in O
horses O
across O
RSA O
during O
2016 O
- O
2017 O
. O
In O
total O
, O
54 O
WNV O
- O
positive O
cases O
were O
identified O
by O
passive O
surveillance O
in O
horses O
with O
febrile O
and/or O
neurological O
signs O
at O
the O
Centre O
for O
Viral O
Zoonoses O
, O
University O
of O
Pretoria O
. O
They O
were O
followed O
up O
and O
compared O
to O
120 O
randomly O
selected O
WNV O
- O
negative O
controls O
with O
the O
same O
case O
definition O
and O
during O
the O
same O
time O
period O
. O
Of O
the O
WNV O
- O
positive O
cases O
, O
52 O
% O
had O
fever O
, O
92 O
% O
displayed O
neurological O
signs O
, O
and O
39 O
% O
experienced O
mortality O
. O
Cases O
occurred O
mostly O
in O
WNV O
- O
unvaccinated O
horses O
< O
5 O
years O
old O
, O
during O
late O
summer O
and O
autumn O
after O
heavy O
rain O
, O
in O
the O
temperate O
to O
warm O
eastern O
parts O
of O
RSA O
. O
WNV O
- O
positive O
cases O
that O
had O
only O
neurological O
signs O
without O
fever O
were O
more O
likely O
to O
die O
. O
In O
the O
multivariable O
analysis O
, O
the O
odds O
of O
WNV O
infection O
were O
associated O
with O
season O
( O
late O
summer O
) O
, O
higher O
altitude O
, O
more O
highly O
purebred O
animals O
, O
younger O
age O
, O
and O
failure O
to O
vaccinate O
against O
WNV O
. O
Vaccination O
is O
currently O
the O
most O
effective O
prophylactic O
measure O
to O
reduce O
WNV O
morbidity O
and O
mortality O
in O
horses O
. O
Objective O
To O
determine O
the O
prevalence B-EPI
, O
profile O
and O
predictors O
of O
infections O
in O
an O
Indian O
cohort O
of O
IIM O
. O
Methods O
We O
reviewed O
the O
records O
of O
a O
retrospective O
cohort O
of O
IIM O
enrolled O
from O
consecutive O
patients O
following O
up O
in O
the O
clinic O
as O
the O
observation O
cohort O
( O
OC O
) O
. O
A O
newly O
diagnosed O
inception O
cohort O
of O
IIM O
were O
followed O
prospectively O
as O
the O
validation O
cohort O
( O
VC O
) O
to O
confirm O
observations O
and O
compare O
with O
the O
OC O
. O
Results O
Among O
68 O
patients O
in O
the O
OC O
( O
age O
33.4 O
years O
, O
F O
: O
M O
4.2:1 O
) O
, O
37(54.4 O
% O
) O
experienced O
54 O
infections O
, O
of O
which O
21(38.8 O
% O
) O
were O
major O
and O
recurrent O
infections O
in O
11 O
patients(16.17 O
% O
) O
over O
3.08 O
years O
. O
Tuberculosis O
was O
the O
most O
common O
infection(12 O
, O
22.2 O
% O
) O
, O
with O
predominance O
of O
extra O
- O
pulmonary O
forms O
. O
Serum O
protein(OR O
0.44 O
) O
, O
platelets(0.44 O
) O
at O
disease O
onset O
and O
daily O
steroid O
dose(1.04 O
) O
predicted O
major O
infections O
on O
multivariate O
analysis O
. O
A O
higher O
daily O
dose O
of O
steroids O
at O
first O
infection O
correlated O
with O
number O
of O
recurrent O
infections O
. O
Infection O
free O
one O
- O
year O
survival O
was O
73.8%.Of O
70 O
patients O
in O
VC O
( O
35.7 O
years O
, O
F O
: O
M O
3.7:1 O
) O
, O
three O
had O
myositis O
attributed O
to O
an O
infection O
. O
Similar O
proportion O
of O
total(22 O
, O
33.3 O
% O
) O
, O
major(10 O
, O
45.4 O
% O
) O
and O
recurrent(4,18 O
% O
) O
infections O
were O
recorded O
. O
Most O
common O
infection O
was O
community O
acquired O
pneumonia O
, O
followed O
by O
Tuberculosis O
with O
serum O
albumin(OR O
0.25 O
) O
at O
disease O
onset O
being O
the O
only O
predictor O
. O
One O
- O
year O
infection O
free O
survival O
was O
64.7 B-STAT
% I-STAT
. O
Those O
who O
had O
a O
major O
infection O
had O
increased O
mortality O
at O
1 O
year O
with O
survival O
of O
60 O
% O
compared O
with O
89.09 O
% O
in O
those O
without O
. O
In O
both O
cohorts O
, O
a O
daily O
prednisone O
dose O
> O
6.25 O
mg O
predisposed O
to O
major O
infections O
. O
Conclusion O
Major O
and O
recurrent O
infections O
are O
common O
in O
Indian O
IIM O
patients O
and O
confer O
higher O
risk O
for O
future O
infections O
and O
lower O
survival O
. O
Respiratory O
and O
atypical O
bacterial O
infections O
such O
as O
Tuberculosis O
occur O
throughout O
the O
disease O
course O
. O
Over O
the O
last O
50 O
years O
, O
significant O
muskrat O
( O
Ondatra O
zibethicus O
) O
harvest O
declines O
have O
been O
observed O
throughout O
North B-LOC
America I-LOC
. O
Several O
theories O
for O
the O
decline O
have O
been O
proposed O
, O
including O
increased O
parasite O
infections O
and O
disease O
within O
muskrat O
populations O
. O
No O
existing O
wholistic O
review O
of O
muskrat O
exposure O
to O
pathogens O
, O
contaminants O
, O
and O
diseases O
exists O
. O
To O
address O
this O
knowledge O
gap O
, O
we O
conducted O
a O
thorough O
review O
of O
existing O
literature O
on O
muskrat O
pathogens O
, O
contaminants O
, O
and O
diseases O
across O
their O
natural O
range O
. O
This O
review O
is O
comprised O
of O
131 O
articles O
from O
1915 O
to O
2019 O
and O
from O
27 O
U.S. B-LOC
states O
and O
9 O
Canadian O
provinces O
. O
A O
wide O
diversity O
of O
contaminants O
, O
toxins O
, O
and O
pathogens O
were O
reported O
in O
muskrats O
, O
with O
the O
most O
common O
diseases O
being O
cysticercosis O
, O
tularemia O
, O
Tyzzer O
's O
disease O
, O
and O
biotoxin O
poisoning O
from O
cyanobacteria O
. O
This O
review O
provides O
a O
summary O
of O
muskrat O
pathogens O
, O
contaminants O
, O
and O
diseases O
over O
a O
century O
that O
has O
observed O
significant O
population O
declines O
throughout O
the O
species O
' O
range O
in O
North B-LOC
America I-LOC
. O
Such O
data O
provide O
a O
baseline O
for O
understanding O
the O
potential O
role O
of O
disease O
in O
these O
declines O
. O
In O
addition O
, O
these O
data O
highlight O
critical O
knowledge O
gaps O
that O
warrant O
future O
research O
efforts O
. O
Pulmonary O
agenesis O
is O
a O
rarely O
encountered O
congenital O
anomaly O
, O
and O
its O
average B-EPI
prevalence I-EPI
is O
about O
1 O
in O
100,000 O
births O
. O
Anomalies O
of O
the O
cardiovascular O
, O
musculoskeletal O
, O
gastrointestinal O
, O
or O
genitourinary O
systems O
may O
accompany O
in O
nearly O
half O
of O
the O
cases O
. O
The O
diagnosis O
of O
pulmonary O
agenesis O
is O
usually O
made O
during O
childhood O
, O
but O
the O
diagnosis O
may O
be O
delayed O
until O
adulthood O
in O
case O
of O
an O
absence O
of O
comorbid O
anomalies O
. O
Herein O
, O
we O
present O
a O
case O
of O
pulmonary O
agenesis O
that O
was O
diagnosed O
during O
adulthood O
. O
CT O
- O
based O
quantitative O
analysis O
of O
any O
ossification O
center O
in O
the O
cranium O
has O
not O
previously O
been O
carried O
out O
due O
to O
the O
limited O
availability O
of O
human O
fetal O
material O
. O
Detailed O
morphometric O
data O
on O
the O
development O
of O
ossification O
centers O
in O
the O
human O
fetus O
may O
be O
useful O
in O
the O
early O
detection O
of O
congenital O
defects O
. O
Ossification O
disorders O
in O
the O
cranium O
are O
associated O
with O
either O
a O
delayed O
development O
of O
ossification O
centers O
or O
their O
mineralization O
. O
These O
aberrations O
may O
result O
in O
the O
formation O
of O
accessory O
skull O
bones O
that O
differ O
in O
shape O
and O
size O
, O
and O
the O
incidence B-EPI
of O
which O
may O
be O
misdiagnosed O
as O
, O
e.g. O
, O
skull O
fractures O
. O
The O
study O
material O
comprised O
37 O
human O
fetuses O
of O
both O
sexes O
( O
16 O
♂ O
, O
21 B-STAT
♀ I-STAT
) O
aged O
18 O
- O
30 O
weeks O
. O
Using O
CT O
, O
digital O
image O
analysis O
software O
, O
3D O
reconstruction O
and O
statistical O
methods O
, O
the O
linear O
, O
planar O
and O
spatial O
dimensions O
of O
the O
occipital O
squama O
ossification O
center O
were O
measured O
. O
The O
morphometric O
characteristics O
of O
the O
fused O
ossification O
center O
of O
the O
occipital O
squama O
show O
no O
right O
- O
left O
differences O
. O
In O
relation O
to O
gestational O
age O
, O
the O
ossification O
center O
of O
the O
occipital O
squama O
grows O
linearly O
in O
its O
right O
and O
left O
vertical O
diameters O
, O
logarithmically O
in O
its O
transverse O
diameters O
of O
both O
the O
interparietal O
and O
supraoccipital O
parts O
and O
projection O
surface O
area O
, O
and O
according O
to O
a O
quadratic O
function O
in O
its O
volume O
. O
The O
obtained O
numerical O
findings O
of O
the O
occipital O
squama O
ossification O
center O
may O
be O
considered O
age O
- O
specific O
references O
of O
relevance O
in O
both O
the O
estimation O
of O
gestational O
age O
and O
the O
diagnostic O
process O
of O
congenital O
defects O
. O
The O
congenital O
long O
QT O
syndrome O
( O
LQTS O
) O
is O
an O
inherited O
cardiac O
disorder O
characterized O
by O
increased O
QT O
intervals O
and O
a O
tendency O
to O
experience O
ventricular O
tachycardia O
, O
which O
can O
cause O
fainting O
, O
heart O
failure O
, O
or O
sudden O
death O
. O
A O
4 O
- O
year O
- O
old O
female O
patient O
undergoing O
velopharyngeal O
correction O
surgery O
under O
general O
anesthesia O
suddenly O
developed O
Torsades O
de O
pointes O
. O
Although O
the O
patient O
spontaneously O
resolved O
to O
sinus O
rhythm O
without O
treatment O
, O
subsequent O
QT O
prolongation O
persisted O
. O
Here O
, O
we O
report O
a O
case O
of O
concealed O
LQTS O
with O
a O
literature O
review O
. O
Context O
: O
Gestational O
trophoblastic O
disease O
( O
GTD O
) O
is O
a O
rare O
complication O
of O
pregnancy O
, O
ranging O
from O
molar O
pregnancy O
to O
choriocarcinoma O
. O
Twin O
pregnancies O
with O
GTD O
and O
coexisting O
normal O
fetus O
are O
extremely O
rare O
with O
an O
estimated B-EPI
incidence I-EPI
of O
1 B-STAT
case I-STAT
per I-STAT
22,000 I-STAT
- I-STAT
100,000 I-STAT
pregnancies O
. O
Molecular O
mimicry O
between O
human O
chorionic O
gonadotrophin O
( O
hCG O
) O
and O
thyroid O
- O
stimulating O
hormone O
( O
TSH O
) O
leads O
to O
gestational O
trophoblastic O
hyperthyroidism O
( O
GTH O
) O
which O
is O
further O
associated O
with O
increased O
maternal O
and O
fetal O
complications O
. O
This O
is O
the O
first O
reported O
case O
in O
literature O
describing O
the O
delivery O
of O
a O
baby O
with O
biochemical O
euthyroid O
status O
following O
a O
twin O
pregnancy O
with O
hydatidiform O
mole O
( O
HM O
) O
associated O
with O
gestational O
trophoblastic O
hyperthyroidism O
( O
GTH O
) O
. O
Case O
Description O
: O
A O
24 O
- O
year O
- O
old O
G4 O
P3 O
Caucasian O
female O
with O
twin O
gestation O
was O
admitted O
to O
hospital O
for O
gestation O
trophoblastic O
hyperthyroidism O
. O
She O
was O
later O
diagnosed O
to O
have O
twin O
pregnancy O
with O
complete O
mole O
and O
coexisting O
normal O
fetus O
complicated O
by O
gestational O
trophoblastic O
hyperthyroidism O
( O
GTH O
) O
. O
Despite O
the O
risk O
associated O
with O
the O
continuation O
of O
molar O
pregnancy O
, O
per O
patient O
request O
, O
pregnancy O
was O
continued O
till O
viability O
of O
the O
fetus O
. O
The O
patient O
underwent O
cesarean O
section O
due O
to O
worsening O
preeclampsia O
and O
delivered O
a O
euthyroid O
baby O
at O
the O
24th O
week O
of O
gestation O
. O
Conclusions O
: O
Twin O
pregnancy O
with O
gestational O
trophoblastic O
disease O
and O
coexisting O
normal O
fetus O
is O
associated O
with O
high O
risk O
of O
hyperthyroidism O
, O
and O
careful O
monitoring O
of O
the O
thyroid O
function O
test O
along O
with O
dose O
titration O
of O
thionamides O
is O
of O
utmost O
importance O
throughout O
the O
gestation O
. O
If O
normal O
thyroid O
hormone O
levels O
are O
maintained O
during O
the O
pregnancy O
, O
euthyroidism O
could O
be O
successfully O
achieved O
in O
the O
baby O
. O
Background O
Nonalcoholic O
steatohepatitis O
( O
NASH O
) O
is O
a O
subtype O
of O
non O
- O
alcoholic O
fatty O
liver O
disease O
( O
NAFLD O
) O
with O
a O
potentially O
progressive O
course O
to O
liver O
fibrosis O
, O
cirrhosis O
with O
its O
complications O
, O
or O
even O
hepatocellular O
carcinoma O
. O
NAFLD O
is O
a O
rapidly O
growing O
chronic O
liver O
disease O
, O
with O
a O
global B-LOC
prevalence B-EPI
of O
about O
25 O
% O
, O
with O
a O
significant O
increase O
in O
the O
last O
2 O
decades O
, O
changing O
the O
landscape O
of O
hepatology O
. O
This O
study O
aimed O
to O
undertake O
a O
bibliometric O
global O
analysis O
of O
research O
literature O
focusing O
on O
NASH O
. O
Methods O
We O
searched O
the O
Scopus O
database O
to O
identify O
all O
articles O
pertaining O
to O
O
non O
- O
alcoholic O
steatohepatitis O
O
or O
O
NASH O
O
- O
the O
2 O
keywords O
used O
to O
search O
in O
the O
title O
or O
abstract O
within O
the O
time O
period O
1980 O
to O
2018 O
. O
The O
collected O
data O
included O
document O
type O
, O
author O
, O
journal O
, O
publication O
year O
, O
citation O
reports O
, O
country O
, O
and O
were O
analyzed O
using O
Microsoft O
Excel O
and O
Microsoft O
Word O
. O
Results O
A O
total O
number O
of O
6632 O
articles O
published O
in O
1355 O
journals O
were O
retrieved O
. O
English O
was O
the O
predominant O
language O
of O
publication O
, O
USA B-LOC
being O
the O
most O
productive O
with O
1937 O
articles O
published O
( O
29.2 O
% O
of O
the O
total O
number O
of O
publications O
) O
, O
followed O
by O
Japan B-LOC
with O
909 O
, O
representing O
13.7 O
% O
of O
publications O
. O
Hepatology O
, O
Journal O
of O
Hepatology O
and O
World O
Journal O
of O
Gastroenterology O
were O
the O
most O
active O
journals O
. O
Research O
articles O
were O
the O
most O
common O
type O
of O
publications O
( O
4524 B-STAT
; O
68.22 O
% O
) O
, O
followed O
by O
review O
articles O
( O
1359 O
; O
20.49 O
% O
) O
. O
The O
total O
number O
of O
citations O
received O
by O
all O
publications O
was O
274,041 O
, O
with O
an O
average O
of O
41.32 B-STAT
per I-STAT
article I-STAT
( I-STAT
range O
: O
0 O
- O
4384 O
) O
. O
The O
average O
number O
of O
authors O
per O
article O
has O
increased O
in O
the O
last O
2 O
decades O
, O
whereas O
the O
trend O
of O
single- O
( O
or O
few O
) O
authored O
publications O
has O
decreased O
. O
Conclusion O
This O
study O
indicates O
that O
NASH O
is O
a O
significant O
topic O
in O
the O
hepatology O
research O
, O
as O
proved O
by O
the O
huge O
number O
of O
publications O
, O
recording O
an O
exponential O
growth O
in O
the O
last O
2 O
decades O
. O
The O
USA B-LOC
stands O
out O
as O
by O
far O
the O
most O
productive O
country O
. O
Aim O
Heart O
failure O
is O
increasing O
in O
Japan B-LOC
, O
in O
particular O
that O
with O
preserved O
ejection O
fraction O
( O
HFpEF O
) O
prevalent B-EPI
in O
older O
- O
aged O
patients O
. O
The O
purpose O
of O
this O
study O
was O
to O
investigate O
the O
pathophysiology O
during O
the O
early O
stage O
of O
left O
ventricular O
( O
LV O
) O
diastolic O
dysfunction O
by O
the O
quantitative O
proteome O
analysis O
of O
human O
myocardium O
. O
Methods O
Among O
331 O
post O
- O
mortem O
autopsy O
patients O
, O
we O
selected O
23 O
patients O
( O
aged O
79 O
± O
9.6 O
years O
) O
with O
echocardiographic O
data O
and O
without O
major O
comorbidities O
, O
except O
hypertension O
. O
Cryopreserved O
autopsy O
tissue O
of O
the O
LV O
myocardium O
was O
subjected O
to O
proteome O
analysis O
. O
LV O
diastolic O
function O
was O
evaluated O
by O
echocardiographic O
data O
. O
Thirteen O
patients O
were O
classified O
into O
the O
impaired O
diastolic O
function O
( O
IDF O
) O
group O
, O
and O
10 O
the O
normal O
cardiac O
function O
group O
. O
We O
performed O
comparative O
proteome O
analysis O
between O
the O
IDF O
and O
normal O
groups O
by O
isobaric O
tags O
for O
relative O
and O
absolute O
quantitation O
( O
iTRAQ O
) O
using O
nano O
- O
liquid O
chromatography O
- O
tandem O
mass O
spectrometry O
. O
Results O
The O
iTRAQ O
- O
based O
proteome O
analysis O
revealed O
57 O
differentially O
expressed O
proteins O
in O
the O
IDF O
group O
. O
Molecular O
network O
analysis O
of O
differentially O
expressed O
proteins O
indicated O
that O
endoplasmic O
reticulum O
( O
ER O
) O
stress O
was O
a O
potentially O
important O
event O
. O
Furthermore O
, O
the O
expressions O
of O
proteins O
associated O
with O
the O
ER O
stress O
response O
, O
such O
as O
glucose O
- O
regulated O
protein O
78 O
kDa O
, O
inositol O
- O
requiring O
kinase O
1α O
and O
spliced O
X O
- O
box O
binding O
protein O
1 B-STAT
, I-STAT
were O
significantly O
decreased O
in O
the O
IDF O
group O
. O
Conclusions O
This O
study O
suggested O
that O
reduced O
ER O
stress O
responses O
were O
involved O
during O
the O
early O
stage O
of O
LV O
diastolic O
dysfunction O
. O
Geriatr O
Gerontol O
Int O
•• O
; O
•• O
: O
••-•• O
Geriatr O
Gerontol O
Int O
2021 O
; O
•• O
: O
••-••. O
Although O
benzothiazole O
and O
its O
derivatives O
( O
BTHs O
) O
are O
considered O
emerging O
contaminants O
in O
diverse O
environments O
and O
organisms O
, O
little O
information O
is O
available O
about O
their O
contamination O
profiles O
and O
health O
impact O
in O
ambient O
particles O
. O
In O
this O
study O
, O
an O
optimized O
method O
of O
ultrasound O
- O
assisted O
extraction O
coupled O
with O
the O
selected O
reaction O
monitoring O
( O
SRM O
) O
mode O
of O
GC O
- O
EI O
- O
MS O
/ O
MS O
was O
applied O
to O
characterize O
and O
analyze O
PM O
2.5 O
-bound O
BTHs O
from O
three O
cities O
of O
China B-LOC
( O
Guangzhou B-LOC
, O
Shanghai B-LOC
, O
and O
Taiyuan B-LOC
) O
during O
the O
winter O
of O
2018 O
. O
The O
total O
BTH O
concentration O
( O
ΣBTHs O
) O
in O
PM O
2.5 O
samples O
from O
the O
three O
cities O
decreased O
in O
the O
order O
of O
Guangzhou B-LOC
> O
Shanghai O
> O
Taiyuan O
, O
independently O
of O
the O
PM O
2.5 O
concentration O
. O
Despite O
the O
large O
variation O
in O
concentration O
of O
ΣBTHs O
in O
PM O
2.5 O
, O
2 O
- O
hydroxybenzothiazole O
( O
OTH O
) O
was O
always O
the O
predominant O
compound O
among O
the O
PM O
2.5 O
-bound O
BTHs O
and O
accounted O
for O
50 B-STAT
- O
80 O
% O
of O
total O
BTHs O
in O
the O
three O
regions O
. O
Results O
from O
human O
exposure O
assessment O
and O
toxicity O
screening O
indicated O
that O
the O
outdoor O
exposure O
risk O
of O
PM O
2.5 O
-bound O
BTHs O
in O
toddlers O
was O
much O
higher O
than O
in O
adults O
, O
especially O
for O
OTH O
. O
The O
developmental O
and O
reproduction O
toxicity O
of O
OTH O
was O
further O
explored O
in O
vivo O
and O
in O
vitro O
. O
Exposure O
of O
mouse O
embryonic O
stem O
cells O
( O
mESCs O
) O
to O
OTH O
for O
48 O
h O
significantly O
increased O
the O
intracellular O
reactive O
oxygen O
species O
( O
ROS O
) O
and O
induced O
DNA O
damage O
and O
apoptosis O
via O
the O
functionally O
activating O
p53 O
expression O
. O
In O
addition O
, O
the O
growth O
and O
development O
of O
zebrafish O
embryos O
were O
found O
to O
be O
severely O
affected O
after O
OTH O
treatment O
. O
An O
overall O
metabolomics O
study O
was O
conducted O
on O
the O
exposed O
zebrafish O
larvae O
. O
The O
results O
indicated O
that O
exposure O
to O
OTH O
inhibited O
the O
phenylalanine O
hydroxylation O
reaction O
, O
which O
further O
increased O
the O
accumulation O
of O
toxic O
phenylpyruvate O
and O
acetylphenylalanine O
in O
zebrafish O
. O
These O
findings O
provide O
important O
insights O
into O
the O
contamination O
profiles O
of O
PM O
2.5 O
-bound O
BTHs O
and O
emphasize O
the O
health O
risk O
of O
OTH O
. O
Barth O
syndrome O
( O
BTHS O
) O
is O
a O
rare O
, O
X O
- O
linked O
recessive O
, O
infantile O
- O
onset O
debilitating O
disorder O
characterized O
by O
early O
- O
onset O
cardiomyopathy O
, O
skeletal O
muscle O
myopathy O
, O
growth O
delay O
, O
and O
neutropenia O
, O
with O
a O
worldwide B-LOC
incidence B-EPI
of O
1/300,000 B-STAT
- O
400,000 O
live O
births O
. O
The O
high O
mortality O
rate O
throughout O
infancy O
in O
BTHS O
patients O
is O
related O
primarily O
to O
progressive O
cardiomyopathy O
and O
a O
weakened O
immune O
system O
. O
BTHS O
is O
caused O
by O
defects O
in O
the O
TAZ O
gene O
that O
encodes O
tafazzin O
, O
a O
transacylase O
responsible O
for O
the O
remodeling O
and O
maturation O
of O
the O
mitochondrial O
phospholipid O
cardiolipin O
( O
CL O
) O
, O
which O
is O
critical O
to O
normal O
mitochondrial O
structure O
and O
function O
( O
i.e. O
, O
ATP O
generation O
) O
. O
A O
deficiency O
in O
tafazzin O
results O
in O
up O
to O
a O
95 O
% O
reduction O
in O
levels O
of O
structurally O
mature O
CL O
. O
Because O
the O
heart O
is O
the O
most O
metabolically O
active O
organ O
in O
the O
body O
, O
with O
the O
highest O
mitochondrial O
content O
of O
any O
tissue O
, O
mitochondrial O
dysfunction O
plays O
a O
key O
role O
in O
the O
development O
of O
heart O
failure O
in O
patients O
with O
BTHS O
. O
Changes O
in O
mitochondrial O
oxidative O
phosphorylation O
reduce O
the O
ability O
of O
mitochondria O
to O
meet O
the O
ATP O
demands O
of O
the O
human O
heart O
as O
well O
as O
skeletal O
muscle O
, O
namely O
ATP O
synthesis O
does O
not O
match O
the O
rate O
of O
ATP O
consumption O
. O
The O
presence O
of O
several O
cardiomyopathic O
phenotypes O
have O
been O
described O
in O
BTHS O
, O
including O
dilated O
cardiomyopathy O
, O
left O
ventricular O
noncompaction O
, O
either O
alone O
or O
in O
conjunction O
with O
other O
cardiomyopathic O
phenotypes O
, O
endocardial O
fibroelastosis O
, O
hypertrophic O
cardiomyopathy O
, O
and O
an O
apical O
form O
of O
hypertrophic O
cardiomyopathy O
, O
among O
others O
, O
all O
of O
which O
can O
be O
directly O
attributed O
to O
the O
lack O
of O
CL O
synthesis O
, O
remodeling O
, O
and O
maturation O
with O
subsequent O
mitochondrial O
dysfunction O
. O
Several O
mechanisms O
by O
which O
these O
cardiomyopathic O
phenotypes O
exist O
have O
been O
proposed O
, O
thereby O
identifying O
potential O
targets O
for O
treatment O
. O
Dysfunction O
of O
the O
sarcoplasmic O
reticulum O
Ca O
2 O
+ O
-ATPase O
pump O
and O
inflammation O
potentially O
triggered O
by O
circulating O
mitochondrial O
components O
have O
been O
identified O
. O
Currently O
, O
treatment O
modalities O
are O
aimed O
at O
addressing O
symptomatology O
of O
HF O
in O
BTHS O
, O
but O
do O
not O
address O
the O
underlying O
pathology O
. O
One O
novel O
therapeutic O
approach O
includes O
elamipretide O
, O
which O
crosses O
the O
mitochondrial O
outer O
membrane O
to O
localize O
to O
the O
inner O
membrane O
where O
it O
associates O
with O
cardiolipin O
to O
enhance O
ATP O
synthesis O
in O
several O
organs O
, O
including O
the O
heart O
. O
Encouraging O
clinical O
results O
of O
the O
use O
of O
elamipretide O
in O
treating O
patients O
with O
BTHS O
support O
the O
potential O
use O
of O
this O
drug O
for O
management O
of O
this O
rare O
disease O
. O
In O
1978 O
, O
Sohar O
et O
al O
. O
described O
a O
strikingly O
peculiar O
syndrome O
in O
two O
Israeli O
sisters O
. O
These O
young O
women O
responded O
to O
environmental O
temperatures O
of O
18 O
degrees O
C-7 O
degrees O
C O
with O
profuse O
sweating O
on O
large O
segments O
on O
their O
back O
and O
chest O
. O
Both O
had O
additional O
abnormalities O
, O
including O
a O
high O
- O
arched O
palate O
, O
nasal O
voice O
, O
depressed O
nasal O
bridge O
, O
inability O
to O
fully O
extend O
their O
elbows O
, O
and O
kyphoscoliosis O
. O
We O
have O
observed O
this O
disorder O
in O
two O
Norwegian O
brothers O
. O
Genome O
- O
wide O
screening O
in O
the O
two O
families O
, O
followed O
by O
saturation O
marker O
studies O
and O
linkage O
analysis O
, O
identified O
a O
1.4 O
- O
Mb O
homozygous O
candidate O
region O
on O
chromosome O
19p12 O
. O
The O
maximum O
multipoint O
LOD O
score O
was O
4.22 O
. O
In O
both O
families O
, O
DNA O
sequencing O
of O
25 O
genes O
within O
the O
candidate O
region O
identified O
potentially O
deleterious O
CRLF1 O
sequence O
variants O
that O
were O
not O
found O
in O
unaffected O
control O
individuals O
. O
Our O
findings O
confirm O
that O
the O
cold O
- O
induced O
sweating O
syndrome O
is O
an O
autosomal O
recessive O
disorder O
that O
is O
probably O
caused O
by O
impaired O
function O
of O
the O
CRLF1 O
gene O
, O
and O
they O
suggest O
important O
developmental O
functions O
for O
human O
CRLF1 O
. O
Clinical O
/ O
methodological O
issue O
Brain O
tumors O
are O
the O
most O
common O
solid O
tumors O
in O
childhood O
and O
the O
most O
frequent O
cancer O
after O
leukemia O
. O
The O
incidence B-EPI
is O
continuously O
increasing O
. O
The O
WHO O
classification O
of O
brain O
tumors O
, O
valid O
since O
2016 O
, O
is O
now O
based O
on O
the O
combination O
of O
histological O
and O
molecular O
genetic O
diagnostics O
. O
Standard O
radiological O
methods O
Diagnostics O
are O
mainly O
performed O
with O
magnetic O
resonance O
imaging O
( O
MRI O
) O
; O
only O
in O
emergencies O
with O
computed O
tomography O
( O
CT O
) O
. O
Methodological O
innovations O
Diffusion O
and O
susceptibility O
weighted O
and O
dynamic O
contrast O
- O
enhanced O
imaging O
and O
spectroscopy O
are O
used O
. O
Performance O
Improved O
diagnosis O
regarding O
dignity O
, O
size O
determination O
, O
adjacency O
assessment O
, O
and O
morphological O
description O
of O
tumor O
composition O
. O
Achievements O
Modern O
MRI O
with O
functional O
techniques O
is O
now O
the O
gold O
standard O
for O
differential O
diagnosis O
and O
staging O
of O
central O
nervous O
system O
( O
CNS O
) O
tumors O
in O
pediatrics O
. O
The O
prevalence B-EPI
of O
diabetes O
continues O
to O
rise O
worldwide B-LOC
. O
In O
addition O
to O
rising O
rates O
of O
diabetic O
kidney O
disease O
, O
we O
are O
also O
seeing O
a O
parallel O
rise O
in O
nondiabetic O
kidney O
disease O
among O
patients O
with O
diabetes O
. O
These O
nondiabetic O
lesions O
include O
focal O
segmental O
glomerulosclerosis O
, O
IgA O
nephropathy O
, O
membranous O
nephropathy O
, O
and O
other O
glomerular O
diseases O
. O
The O
management O
of O
diabetic O
kidney O
disease O
is O
rapidly O
evolving O
to O
include O
, O
beyond O
glycemic O
control O
and O
renin O
angiotensin O
inhibition O
, O
the O
use O
of O
sodium O
- O
glucose O
cotransporter O
2 O
( O
SGLT2 O
) O
inhibitors O
and O
mineralocorticoid O
receptor O
antagonists O
. O
These O
and O
other O
new O
treatment O
strategies O
should O
be O
applicable O
to O
managing O
glomerular O
disease O
in O
diabetic O
patients O
to O
reduce O
toxicities O
associated O
with O
immunosuppression O
and O
, O
in O
particular O
, O
corticosteroids O
. O
The O
prevalence B-EPI
of O
glomerular O
disease O
in O
diabetic O
patients O
is O
underappreciated O
. O
Diagnosis O
and O
appropriately O
treating O
these O
diseases O
remain O
an O
important O
avenue O
to O
modify O
kidney O
outcomes O
in O
diabetic O
patients O
. O
Rationale O
A O
growing O
body O
of O
literature O
has O
identified O
a O
robust O
relationship O
between O
the O
experience O
of O
racial O
discrimination O
and O
negative O
self O
- O
reported O
physical O
and O
mental O
health O
outcomes O
. O
Objective O
The O
current O
study O
seeks O
to O
identify O
which O
factors O
-at O
the O
community O
level- O
predict O
racial O
disparities O
in O
actual O
disease O
manifestation O
. O
This O
study O
focuses O
on O
the O
extent O
to O
which O
regional O
demographics O
and O
racial O
attitudes O
, O
both O
implicit O
and O
explicit O
, O
are O
associated O
with O
prevalence B-EPI
rates O
of O
several O
diseases O
for O
Black O
and O
White O
patients O
in O
the B-LOC
United I-LOC
States I-LOC
. O
Methods O
Implicit O
and O
explicit O
racial O
attitudes O
obtained O
from O
Project O
Implicit O
( O
Xu O
et O
al O
. O
, O
2017 O
) O
were O
aggregated O
at O
the O
county O
level O
to O
predict O
variation O
in O
the O
prevalence B-EPI
rates O
of O
several O
chronic O
illnesses O
among O
Medicare O
recipients O
. O
Results O
When O
controlling O
for O
economic O
indicators O
, O
Black O
and O
White O
patients O
who O
live O
in O
areas O
with O
high O
implicit O
and O
explicit O
racial O
bias O
tend O
to O
exhibit O
a O
higher O
incidence B-EPI
of O
chronic O
health O
problems O
, O
including O
cancer O
, O
stroke O
, O
asthma O
, O
diabetes O
, O
and O
heart O
failure O
. O
These O
relationships O
tended O
to O
be O
stronger O
for O
Black O
patients O
. O
Additionally O
, O
patients O
in O
racially O
diverse O
and O
racially O
segregated O
regions O
also O
tended O
to O
exhibit O
a O
higher O
incidence B-EPI
of O
chronic O
health O
problems O
. O
Conclusion O
Findings O
from O
the O
study O
highlight O
the O
reliable O
relationship O
between O
both O
racial O
biases O
and O
regional O
demographics O
and O
the O
incidence B-EPI
rates O
of O
several O
chronic O
diseases O
, O
particularly O
in O
Black O
patients O
. O
The O
deficiency O
of O
21 O
- O
hydroxylase O
due O
to O
CYP21A2 O
pathogenic O
variants O
is O
a O
rather O
frequent O
disease O
with O
serious O
consequences O
, O
going O
from O
a O
real O
mortality O
risk O
to O
infertility O
and O
to O
milder O
symptoms O
, O
nevertheless O
important O
for O
affecting O
the O
patients O
' O
self O
- O
esteem O
. O
In O
the O
most O
severe O
cases O
life O
- O
threatening O
adrenal O
salt O
wasting O
crises O
may O
occur O
. O
Significant O
morbidity O
including O
the O
possibility O
of O
mistaken O
gender O
determination O
, O
precocious O
puberty O
, O
infertility O
and O
growth O
arrest O
with O
consequent O
short O
stature O
may O
also O
affect O
these O
patients O
. O
In O
the O
less O
severe O
cases O
milder O
symptoms O
like O
hirsutism O
will O
likely O
affect O
the O
image O
of O
the O
self O
with O
strong O
psychological O
consequences O
. O
Its O
diagnosis O
is O
confirmed O
by O
17OH O
- O
progesterone O
dosages O
exceeding O
the O
cut O
- O
off O
value O
of O
10/15 B-STAT
ng O
/ O
ml O
but O
genotyping O
is O
progressively O
assuming O
an O
essential O
role O
in O
the O
study O
of O
these O
patients O
particularly O
in O
confirming O
difficult O
cases O
, O
determining O
some O
aspects O
of O
the O
prognosis O
and O
allowing O
a O
correct O
genetic O
counseling O
. O
Genotyping O
is O
a O
difficult O
process O
due O
to O
the O
occurrence B-EPI
of O
both O
a O
gene O
and O
a O
highly O
homologous O
pseudo O
gene O
. O
However O
, O
new O
tools O
are O
opening O
new O
possibilities O
to O
this O
analysis O
and O
improving O
the O
chances O
of O
a O
correct O
diagnosis O
and O
better O
understanding O
of O
the O
underlying O
mechanisms O
of O
the O
disease O
. O
Beyond O
the O
10 O
classic O
pathogenic O
variants O
usually O
searched O
for O
in O
most O
laboratories O
, O
a O
correct O
analysis O
of O
21OH O
- O
deficiency O
cases O
implies O
completely O
sequencing O
of O
the O
entire O
gene O
and O
the O
determination O
of O
gene O
duplications O
. O
These O
are O
now O
recognized O
to O
occur O
frequently O
and O
can O
be O
responsible O
for O
some O
false O
positive O
cases O
. O
And O
finally O
, O
because O
gene O
conversions O
can O
include O
several O
pathogenic O
variants O
one O
can O
not O
be O
certain O
of O
identifying O
that O
both O
alleles O
are O
affected O
without O
studying O
parental O
DNA O
samples O
. O
A O
complete O
genotype O
characterization O
should O
be O
considered O
essential O
in O
the O
preparation O
for O
pregnancy O
, O
even O
in O
the O
case O
of O
parents O
with O
milder O
forms O
of O
the O
disease O
, O
or O
even O
just O
carriers O
, O
since O
it O
has O
been O
reported O
that O
giving O
birth O
to O
progeny O
with O
the O
severe O
classic O
forms O
occurs B-EPI
with O
a O
much O
higher O
frequency O
than O
expected O
. O
Background O
The O
degenerative O
cerebellar O
ataxias O
comprise O
a O
large O
and O
heterogeneous O
group O
of O
neurological O
diseases O
whose O
hallmark O
clinical O
feature O
is O
ataxia O
, O
and O
which O
are O
accompanied O
, O
to O
variable O
degrees O
, O
by O
other O
features O
that O
are O
attributable O
to O
cerebellar O
dysfunction O
. O
Essential O
tremor O
( O
ET O
) O
is O
an O
exceptionally O
common O
neurological O
disease O
whose O
primary O
motor O
feature O
is O
action O
tremor O
, O
although O
patients O
often O
manifest O
intention O
tremor O
, O
mild O
gait O
ataxia O
and O
several O
other O
features O
of O
cerebellar O
dysfunction O
. O
Main O
body O
In O
this O
paper O
, O
we O
review O
the O
abundant O
evidence O
derived O
from O
clinical O
, O
neuroimaging O
and O
postmortem O
studies O
, O
linking O
ET O
to O
cerebellar O
dysfunction O
. O
Furthermore O
, O
we O
review O
the O
combination O
of O
clinical O
, O
natural O
history O
and O
postmortem O
features O
suggesting O
that O
ET O
is O
neurodegenerative O
. O
We O
then O
compare O
the O
prevalence B-EPI
of O
ET O
( O
400 B-STAT
- I-STAT
900 I-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
) I-STAT
to O
that O
of O
the O
other O
cerebellar O
degenerations O
( O
ranging O
from O
< O
0.5 B-STAT
- I-STAT
9 I-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
, I-STAT
and O
in O
composite O
likely O
to O
be O
on O
the O
order O
of O
20 B-STAT
cases I-STAT
per I-STAT
100,000 I-STAT
) I-STAT
and O
conclude O
that O
ET O
is O
20 O
to O
45 O
times O
more O
prevalent B-EPI
than O
all O
other O
forms O
of O
cerebellar O
degeneration O
combined O
. O
Conclusion O
Given O
the O
data O
we O
present O
, O
it O
is O
logical O
to O
conclude O
that O
ET O
is O
, O
by O
far O
, O
the O
most O
common O
form O
of O
cerebellar O
degeneration O
. O
Background O
Cardiac O
rupture O
( O
CR O
) O
is O
a O
fatal O
complication O
of O
ST B-LOC
- O
elevation O
myocardial O
infarction O
( O
STEMI O
) O
with O
its O
incidence B-EPI
markedly O
declined O
in O
the O
recent O
decades O
. O
However O
, O
clinical O
features O
of O
CR O
patients O
now O
and O
the O
effect O
of O
reperfusion O
therapy O
to O
CR O
remain O
unclear O
. O
We O
investigated O
the O
clinical O
features O
of O
CR O
in O
STEMI O
patients O
and O
the O
effect O
of O
reperfusion O
therapy O
to O
CR O
in O
mice O
. O
Methods O
Two O
studies O
were O
conducted O
. O
In O
clinical O
study O
, O
data O
of O
1456 O
STEMI O
patients O
admitted O
to O
the O
First O
Hospital O
, O
Xi'an O
Jiaotong O
University O
during O
2015.12 O
. O
~ O
2018.12 O
. O
were O
analyzed O
. O
In O
experimental O
study O
, O
83 O
male O
C57BL/6 O
mice O
were O
operated O
to O
induce O
MI O
. O
Of O
them O
, O
39 O
mice O
were O
permanent O
MI O
( O
group-1 O
) O
, O
and O
remaining O
mice O
received O
reperfusion O
after O
1 O
h O
ischemia O
( O
21 O
mice O
, O
group-2 O
) O
or O
4 O
h O
ischemia O
( O
23 O
mice O
, O
group-3 O
) O
. O
All O
operated O
mice O
were O
monitored O
up O
to O
day-10 O
. O
Animals O
were O
inspected O
three O
times O
daily O
for O
the O
incidence B-EPI
of O
death O
and O
autopsy O
was O
done O
for O
all O
mice O
found O
died O
to O
determine O
the O
cause O
of O
death O
. O
Results O
CR O
was O
diagnosed O
in O
40 O
patients O
: O
free O
- O
wall O
rupture O
in O
17 O
, O
ventricular O
septal O
rupture O
in O
20 O
, O
and O
combined O
locations O
in O
3 O
cases O
. O
CR O
presented O
in O
19 O
patients O
at O
admission O
and O
diagnosed O
in O
another O
21 O
patients O
during O
1 O
~ O
14 O
days O
post O
- O
STEMI O
, O
giving O
an O
in O
- O
hospital O
incidence B-EPI
of O
1.4 B-STAT
% I-STAT
. O
The O
mortality O
of O
CR O
patients O
was O
high O
during O
hospitalization O
accounting O
for O
39 O
% O
of O
total O
in O
- O
hospital O
death O
. O
By O
multivariate O
logistic O
regression O
analysis O
, O
older O
age O
, O
peak O
CK O
- O
MB O
and O
peak O
hs O
- O
CRP O
were O
independent O
predictors O
of O
CR O
post O
- O
STEMI O
. O
In O
mice O
with O
non O
- O
reperfused O
MI O
, O
17 O
animals O
( O
43.6 O
% O
) O
died O
of O
CR O
that O
occurred O
during O
3 O
- O
6 O
days O
post O
- O
MI O
. O
In O
MI O
mice O
received O
early O
or O
delayed O
reperfusion O
, O
all O
mice O
survived O
to O
the O
end O
of O
experiment O
except O
one O
mouse O
died O
of O
acute O
heart O
failure O
. O
Conclusion O
CR O
remains O
as O
a O
major O
cause O
of O
in O
- O
hospital O
death O
in O
STEMI O
patients O
. O
CR O
patients O
are O
characterized O
of O
being O
elderly O
, O
having O
larger O
infarct O
and O
more O
server O
inflammation O
. O
Experimentally O
, O
reperfusion O
post O
- O
MI O
prevented O
CR O
. O
Purpose O
We O
evaluated O
the O
various O
accompanied O
malformations O
in O
patients O
with O
anal O
atresia O
or O
tracheoesophageal O
fistula O
( O
TEF O
) O
. O
Furthermore O
, O
we O
determined O
the O
prevalence B-EPI
of O
VACTERL O
association O
and O
compared O
the O
clinical O
findings O
with O
those O
of O
patients O
without O
VACTERL O
association O
. O
Methods O
We O
enrolled O
the O
patients O
with O
anal O
atresia O
or O
TEF O
with O
/ O
without O
esophageal O
atresia O
. O
We O
collected O
the O
patient O
data O
pertaining O
to O
accompanied O
vertebral O
, O
cardiovascular O
, O
renal O
or O
limb O
anomalies O
, O
single O
umbilical O
artery O
, O
maternal O
diabetes O
mellitus O
or O
drug O
history O
, O
and O
gene O
research O
. O
Results O
A O
total O
155 O
patients O
( O
65 O
boys O
and O
90 O
girls O
) O
were O
enrolled O
with O
147 O
cases O
of O
anal O
atresia O
, O
3 O
cases O
of O
TEF O
, O
and O
5 O
cases O
of O
anal O
atresia O
with O
TEF O
. O
The O
prevalence B-EPI
of O
accompanied O
anomalies O
was O
67.1 O
% O
in O
cardiovascular O
, O
27.1 O
% O
in O
renal O
, O
9.7 O
% O
in O
vertebral O
, O
2.6 O
% O
in O
limb O
anomalies O
, O
and O
3.9 O
% O
in O
single O
umbilical O
artery O
. O
Thirty O
- O
six O
( O
23.2 O
% O
) O
patients O
were O
diagnosed O
with O
VACTERL O
association O
. O
The O
patients O
with O
VACTERL O
association O
had O
a O
significantly O
higher O
number O
of O
male O
patients O
( O
58.3 O
vs. O
37.0 O
% O
, O
p O
= O
.033 O
) O
and O
single O
umbilical O
artery O
( O
11.1 O
vs. O
1.7 O
% O
, O
p O
= O
.026 O
) O
, O
and O
had O
a O
significantly O
lower O
birth O
weight O
( O
2.8 O
vs. O
3.1 O
kg O
, O
p O
= O
.033 O
) O
than O
the O
patients O
without O
VACTERL O
association O
. O
Genetic O
studies O
were O
performed O
in O
111 O
patients O
, O
and O
8 B-STAT
( O
7.2 O
% O
) O
had O
chromosomal O
abnormalities-3 O
in O
VACTERL O
and O
5 O
in O
no O
VACTERL O
group O
. O
Conclusion O
We O
recommend O
a O
careful O
evaluation O
for O
VACTERL O
association O
in O
patients O
with O
anal O
atresia O
or O
TEF O
. O
It O
is O
particularly O
important O
to O
screen O
for O
a O
single O
umbilical O
artery O
for O
features O
of O
VACTERL O
association O
as O
well O
as O
for O
other O
congenital O
anomalies O
. O
Nonalcoholic O
fatty O
liver O
disease O
( O
NAFLD O
) O
is O
the O
most O
prevalent B-EPI
liver O
disease O
worldwide B-LOC
, O
with O
potential O
causes O
stemming O
from O
obesity O
, O
metabolic O
syndrome O
, O
genetic O
disorders O
, O
and O
drug O
toxicity O
. O
We O
report O
a O
42 O
- O
year O
- O
old O
woman O
with O
lipodystrophy O
and O
NAFLD O
due O
to O
a O
pathogenic O
variant O
in O
the O
LMNA O
( O
D300N O
) O
gene O
. O
This O
case O
report O
attempts O
to O
encourage O
clinicians O
to O
consider O
genetic O
diseases O
, O
specifically O
lipodystrophies O
, O
when O
working O
up O
uncommon O
causes O
of O
NAFLD O
. O
Aim O
Psychogenic O
nonepileptic O
seizures O
( O
PNES O
) O
or O
functional O
seizures O
are O
universal O
phenomena O
. O
However O
, O
data O
on O
their O
epidemiology O
is O
limited O
. O
The O
aim O
of O
the O
current O
study O
was O
to O
review O
the O
literature O
on O
the O
epidemiology O
of O
PNES O
and O
to O
provide O
analytical O
estimates O
of O
its O
incidence B-EPI
and O
prevalence B-EPI
based O
on O
the O
direct O
data O
that O
are O
available O
from O
previous O
studies O
on O
PNES O
. O
Methods O
The O
methods O
of O
this O
work O
had O
two O
parts O
: O
( O
1 O
) O
MEDLINE O
, O
PsycINFO O
, O
and O
Scopus O
from O
inception O
to O
19 O
October O
2019 O
were O
systematically O
searched O
. O
( O
2 O
) O
The O
analytical O
study O
of O
the O
incidence B-EPI
and O
prevalence B-EPI
of O
PNES O
was O
performed O
, O
based O
on O
the O
following O
data O
from O
previous O
studies O
: O
incidence B-EPI
of O
PNES O
, O
duration O
of O
PNES O
before O
making O
a O
diagnosis O
, O
outcome O
and O
mortality O
of O
PNES O
. O
Results O
The O
search O
strategy O
yielded O
five O
articles O
; O
three O
were O
on O
the O
incidence B-EPI
and O
two O
on O
the O
prevalence B-EPI
. O
In O
the O
analytical O
part O
of O
the O
study O
, O
the O
incidence B-EPI
of O
PNES O
was O
calculated O
to O
be O
3.1 O
( O
95 O
% O
Confidence O
Interval O
: O
1.1 B-STAT
- I-STAT
5.1 I-STAT
) I-STAT
per I-STAT
100,000 B-STAT
population I-STAT
per I-STAT
year I-STAT
. O
The O
calculated O
prevalence B-EPI
rate O
of O
PNES O
in O
2019 O
was O
108.5 O
( O
95 O
% O
Confidence O
Interval O
: O
39.2 B-STAT
- I-STAT
177.8 I-STAT
) I-STAT
per I-STAT
100,000 I-STAT
population I-STAT
, O
in O
the O
USA B-LOC
. O
Conclusion O
While O
, O
the O
generalizability O
of O
these O
calculated O
incidence B-EPI
and O
prevalence B-EPI
rates O
to O
other O
places O
in O
the O
world O
is O
limited O
, O
they O
give O
us O
a O
reasonable O
hint O
that O
PNES O
is O
a O
common O
condition O
and O
the O
prevalence B-EPI
is O
much O
more O
than O
that O
it O
was O
thought O
before O
. O
Supplemental O
data O
for O
this O
article O
is O
available O
online O
at O
https://doi.org/10.1080/00207454.2021.1942870 B-LOC
. O
Background O
Studies O
have O
shown O
that O
the O
human O
T O
- O
lymphotropic O
virus O
2 O
( O
HTLV-2 O
) O
is O
endemic O
in O
several O
indigenous O
populations O
of O
the O
Brazilian O
Amazon O
and O
molecular O
analyses O
have O
shown O
the O
exclusive O
presence O
of O
HTLV-2 O
subtype O
2c O
among O
the O
indigenous O
groups O
of O
this O
geographical O
region O
. O
Methods O
The O
present O
study O
characterizes O
the O
prevalence B-EPI
of O
HTLV-2 O
infection O
in O
three O
new O
villages O
of O
the O
Xikrin O
tribe O
, O
in O
the O
Kayapo O
group O
, O
according O
to O
their O
distribution O
by O
sex O
and O
age O
. O
The O
study O
included O
263 O
samples O
from O
individuals O
from O
the O
Kateté O
, O
Djujeko O
and O
Oodjã O
villages O
. O
Plasma O
samples O
were O
tested O
for O
the O
presence O
of O
anti O
- O
HTLV-1/2 O
antibodies O
using O
enzyme O
- O
linked O
immunosorbent O
assays O
( O
ELISA O
) O
. O
Seropositive O
samples O
were O
confirmed O
using O
real O
- O
time O
PCR O
, O
nested O
PCR O
and O
sequencing O
. O
Results O
The O
serological O
and O
molecular O
results O
confirmed O
the O
sole O
presence O
of O
HTLV-2 O
in O
77 B-STAT
( O
29 O
% O
) O
samples O
, O
with O
a O
prevalence B-EPI
of O
38 O
% O
among O
women O
and O
18 O
% O
among O
men O
. O
In O
these O
communities O
, O
it O
was O
found O
that O
the O
prevalence B-EPI
of O
HTLV-2 O
infection O
increased O
with O
age O
. O
Nucleotide O
sequences O
( O
642 O
bp O
, O
5'LTR O
) O
from O
eight O
samples O
were O
subjected O
to O
phylogenetic O
analysis O
by O
the O
neighbor O
- O
joining O
method O
to O
determine O
the O
viral O
subtype O
, O
which O
confirmed O
the O
presence O
of O
HTLV-2c O
. O
Conclusions O
The O
results O
of O
the O
present O
study O
establish O
the O
presence O
of O
HTLV-2 O
infection O
in O
three O
new O
villages O
of O
the O
Xikrin O
tribe O
and O
confirm O
the O
high O
endemicity O
of O
the O
infection O
in O
the O
Kayapo O
indigenous O
group O
of O
the O
Brazilian O
Amazon O
. O
Objective O
To O
assess O
the O
prevalence B-EPI
and O
patterns O
of O
hypodontia O
in O
nonsyndromic O
Pierre O
Robin O
sequence O
( O
PRS O
) O
and O
compare O
it O
with O
hypodontia O
in O
nonsyndromic O
isolated O
cleft O
palates O
and O
isolated O
cleft O
lips O
. O
Design O
Retrospective O
cohort O
study O
. O
Setting O
Alder O
Hey O
Children O
's O
Hospital O
, O
United B-LOC
Kingdom I-LOC
. O
Patients O
Patients O
with O
nonsyndromic O
PRS O
( O
group O
1 O
) O
, O
isolated O
cleft O
palate O
( O
group O
2 O
) O
, O
and O
isolated O
cleft O
lip O
( O
group O
3 O
) O
. O
Main O
outcome O
measures O
Hypodontia O
in O
the O
permanent O
dentition O
assessed O
from O
orthopantomographs O
. O
Results O
A O
total O
of O
154 O
patients O
were O
included O
. O
Group O
1 O
had O
the O
highest O
incidence B-EPI
of O
hypodontia O
with O
47 O
% O
having O
at O
least O
one O
tooth O
congenitally O
absent O
. O
Groups O
2 O
and O
3 O
had O
reduced O
rates O
of O
hypodontia O
with O
27 O
% O
and O
19 O
% O
of O
the O
groups O
missing O
teeth O
, O
respectively O
; O
93 O
% O
of O
cases O
of O
hypodontia O
in O
group O
1 O
involved O
the O
absence O
of O
at O
least O
one O
second O
premolar O
. O
Of O
these O
patients O
, O
there O
was O
found O
to O
be O
bilateral O
agenesis O
of O
second O
premolars O
in O
50 O
% O
of O
cases O
. O
Conclusions O
Patients O
with O
PRS O
and O
cleft O
palates O
are O
more O
likely O
to O
have O
hypodontia O
than O
those O
with O
isolated O
cleft O
palates O
or O
unilateral O
cleft O
lips O
. O
Patients O
with O
PRS O
have O
more O
severe O
hypodontia O
than O
those O
with O
isolated O
cleft O
palates O
or O
unilateral O
cleft O
lips O
. O
Bilateral O
agenesis O
of O
lower O
second O
premolars O
is O
a O
commonly O
seen O
pattern O
among O
patients O
with O
PRS O
. O
In O
this O
large O
UK B-LOC
study O
, O
a O
similar O
prevalence B-EPI
and O
pattern O
of O
hypodontia O
to O
other O
nonsyndromic O
PRS O
populations O
worldwide B-LOC
has O
been O
demonstrated O
. O
Objective O
To O
estimate O
pooled B-EPI
prevalence I-EPI
of O
cognitive O
impairment O
in O
neuromyelitis O
opticaspectrum O
disorders O
( O
NMOSD O
) O
cases O
. O
Methods O
We O
searched O
PubMed O
, O
Scopus O
, O
EMBASE O
, O
Web O
of O
Science O
, O
and O
google O
scholar O
. O
We O
also O
searched O
the O
gray O
literature O
including O
references O
of O
the O
included O
studies O
, O
and O
conference O
abstracts O
which O
were O
published O
up O
to O
20th O
October O
2020 O
. O
The O
search O
strategy O
included O
the O
MeSH O
and O
text O
words O
as O
( O
( O
( O
Cognitive O
Dysfunctions O
) O
OR O
Cognitive O
Impairment O
) O
OR O
Cognitive O
Declines O
) O
OR O
Mild O
Cognitive O
Impairment O
) O
OR O
Mental O
Deterioration O
) O
AND O
( O
Neuromyelitis O
Optica O
spectrum O
disorder O
OR O
NMOSD O
OR O
Devic O
syndrome O
OR O
Neuromyelitis O
Optica O
spectrum O
disorders O
) O
. O
Results O
The O
literature O
search O
revealed O
1830 O
articles O
, O
after O
deleting O
duplicates O
1434 O
remained O
. O
For O
the O
meta O
- O
analysis O
, O
25 O
studies O
were O
included O
. O
Totally O
, O
761 O
NMOSD O
patients O
were O
evaluated O
and O
329 O
patients O
had O
cognitive O
impairment O
. O
Mean O
age O
ranged O
from O
34 O
- O
53 O
years O
. O
The O
prevalence B-EPI
of O
cognitive O
impairment O
ranged O
from O
3 O
% O
to O
75%.The O
pooled B-EPI
prevalence I-EPI
of O
cognitive O
impairment O
was O
44 O
% O
, O
95%CI(35%-54 O
% O
) O
, O
( O
I O
2 B-STAT
= O
89.1 O
% O
, O
P<0.001 O
) O
which O
shows O
a O
high O
statistical O
heterogeneity O
. O
By O
excluding O
the O
abstract O
of O
Jung O
et O
al O
which O
was O
published O
in O
2009 O
, O
we O
found O
that O
the O
pooled B-EPI
prevalence I-EPI
was O
34 O
% O
( O
95 O
% O
CI:31 O
- O
37 O
% O
) O
( O
I O
2 O
= O
0 O
) O
CONCLUSION O
: O
Cognitive O
impairment O
should O
be O
considered O
in O
NMOSD O
patients O
as O
its O
pooled B-EPI
prevalence I-EPI
is O
estimated O
as O
44 B-STAT
% I-STAT
. O
Varicella O
- O
zoster O
virus O
( O
VZV O
) O
is O
a O
teratogen O
that O
can O
cross O
the O
placenta O
and O
cause O
the O
congenital O
varicella O
syndrome O
( O
CVS O
) O
, O
which O
is O
characterised O
by O
multi O
- O
system O
anomalies O
. O
There O
have O
been O
130 O
reported O
cases O
of O
CVS O
from O
1947 O
to O
2013 O
. O
The O
estimated B-EPI
incidence I-EPI
of O
CVS O
was O
0.59 B-STAT
% I-STAT
and O
0.84 B-STAT
% I-STAT
for O
women O
infected O
with O
VZV O
during O
the O
entire O
pregnancy O
and O
for O
those O
infected O
the O
first O
20 O
weeks O
of O
pregnancy O
, O
respectively O
. O
Nine O
cases O
were O
reported O
at O
21 O
- O
27 O
weeks O
of O
gestation O
and O
one O
case O
was O
identified O
at O
36 O
weeks O
. O
Herpes O
zoster O
caused O
CVS O
in O
two O
cases O
. O
Regarding O
treatment O
, O
varicella O
zoster O
immunoglobulin O
treatment O
, O
irrespective O
of O
gestational O
age O
, O
should O
be O
considered O
in O
addition O
to O
antiviral O
drugs O
for O
women O
who O
have O
been O
exposed O
to O
or O
infected O
with O
virus O
. O
Transient O
global O
amnesia O
( O
TGA O
) O
is O
a O
benign O
memory O
disorder O
with O
etiologies O
that O
have O
been O
debated O
for O
a O
long O
time O
. O
The O
prevalence B-EPI
of O
stressful O
events O
before O
a O
TGA O
attack O
makes O
it O
hard O
to O
overlook O
these O
precipitating O
factors O
, O
given O
that O
stress O
has O
the O
potential O
to O
organically O
effect O
the O
brain O
. O
Cortical O
spreading O
depression O
( O
CSD O
) O
was O
proposed O
as O
a O
possible O
cause O
decades O
ago O
. O
Being O
a O
regional O
phenomenon O
, O
CSD O
seems O
to O
affect O
every O
aspect O
of O
the O
micro O
- O
mechanism O
in O
maintaining O
the O
homeostasis O
of O
the O
central O
nervous O
system O
( O
CNS O
) O
. O
Corresponding O
evidence O
regarding O
hemodynamic O
and O
morphological O
changes O
from O
TGA O
and O
CSD O
have O
been O
accumulated O
separately O
, O
but O
the O
resemblance O
between O
the O
two O
has O
not O
been O
systematically O
explored O
so O
far O
, O
which O
is O
surprising O
especially O
considering O
that O
CSD O
had O
been O
confirmed O
to O
cause O
secondary O
damage O
in O
the O
human O
brain O
. O
Thus O
, O
by O
deeply O
delving O
into O
the O
anatomic O
and O
electrophysiological O
properties O
of O
the O
CNS O
, O
the O
CSD O
- O
TGA O
model O
may O
render O
insights O
into O
the O
basic O
pathophysiology O
behind O
the O
façade O
of O
the O
enigmatic O
clinical O
presentation O
. O
Antiretroviral O
therapy O
( O
ART O
) O
has O
significantly O
improved O
life O
expectancy O
of O
infected O
subjects O
, O
generating O
a O
new O
epidemiological O
setting O
of O
people O
aging O
withHuman O
Immunodeficiency O
Virus O
( O
HIV O
) O
. O
People O
living O
with O
HIV O
( O
PLWH O
) O
, O
having O
longer O
life O
expectancy O
, O
now O
face O
several O
age O
- O
related O
conditions O
as O
well O
as O
side O
effects O
of O
long O
- O
term O
exposure O
of O
ART O
. O
Chronic O
kidney O
disease O
( O
CKD O
) O
is O
a O
common O
comorbidity O
in O
this O
population O
. O
CKD O
is O
a O
relentlessly O
progressive O
disease O
that O
may O
evolve O
toward O
end O
- O
stage O
renal O
disease O
( O
ESRD O
) O
and O
significantly O
affect O
quality O
of O
life O
and O
risk O
of O
death O
. O
Herein O
, O
we O
review O
current O
understanding O
of O
renal O
involvement O
in O
PLWH O
, O
mechanisms O
and O
risk O
factors O
for O
CKD O
as O
well O
as O
strategies O
for O
early O
recognition O
of O
renal O
dysfunction O
and O
best O
care O
of O
CKD O
. O
Epilepsy O
is O
common O
in O
early O
childhood O
. O
In O
this O
age O
group O
it O
is O
associated O
with O
high O
rates O
of O
therapy O
- O
resistance O
, O
and O
with O
cognitive O
, O
motor O
, O
and O
behavioural O
comorbidity O
. O
A O
large O
number O
of O
genes O
, O
with O
wide O
ranging O
functions O
, O
are O
implicated O
in O
its O
aetiology O
, O
especially O
in O
those O
with O
therapy O
- O
resistant O
seizures O
. O
Identifying O
the O
more O
common O
single O
- O
gene O
epilepsies O
will O
aid O
in O
targeting O
resources O
, O
the O
prioritization O
of O
diagnostic O
testing O
and O
development O
of O
precision O
therapy O
. O
Previous O
studies O
of O
genetic O
testing O
in O
epilepsy O
have O
not O
been O
prospective O
and O
population O
- O
based O
. O
Therefore O
, O
the O
population O
- O
incidence B-EPI
of O
common O
genetic O
epilepsies O
remains O
unknown O
. O
The O
objective O
of O
this O
study O
was O
to O
describe O
the O
incidence B-EPI
and O
phenotypic O
spectrum O
of O
the O
most O
common O
single O
- O
gene O
epilepsies O
in O
young O
children O
, O
and O
to O
calculate O
what O
proportion O
are O
amenable O
to O
precision O
therapy O
. O
This O
was O
a O
prospective O
national O
epidemiological O
cohort O
study O
. O
All O
children O
presenting O
with O
epilepsy O
before O
36 O
months O
of O
age O
were O
eligible O
. O
Children O
presenting O
with O
recurrent O
prolonged O
( O
> O
10 O
min O
) O
febrile O
seizures O
; O
febrile O
or O
afebrile O
status O
epilepticus O
( O
> O
30 O
min O
) O
; O
or O
with O
clusters O
of O
two O
or O
more O
febrile O
or O
afebrile O
seizures O
within O
a O
24 O
- O
h O
period O
were O
also O
eligible O
. O
Participants O
were O
recruited O
from O
all O
20 O
regional O
paediatric O
departments O
and O
four O
tertiary O
children O
's O
hospitals O
in O
Scotland B-LOC
over O
a O
3 O
- O
year O
period O
. O
DNA O
samples O
were O
tested O
on O
a O
custom O
- O
designed O
104 O
- O
gene O
epilepsy O
panel O
. O
Detailed O
clinical O
information O
was O
systematically O
gathered O
at O
initial O
presentation O
and O
during O
follow O
- O
up O
. O
Clinical O
and O
genetic O
data O
were O
reviewed O
by O
a O
multidisciplinary O
team O
of O
clinicians O
and O
genetic O
scientists O
. O
The O
pathogenic O
significance O
of O
the O
genetic O
variants O
was O
assessed O
in O
accordance O
with O
the O
guidelines O
of O
UK O
Association O
of O
Clinical O
Genetic O
Science O
( O
ACGS O
) O
. O
Of O
the O
343 O
patients O
who O
met O
inclusion O
criteria O
, O
333 O
completed O
genetic O
testing O
, O
and O
80/333 B-STAT
( O
24 O
% O
) O
had O
a O
diagnostic O
genetic O
finding O
. O
The O
overall O
estimated O
annual B-EPI
incidence I-EPI
of O
single O
- O
gene O
epilepsies O
in O
this O
well O
- O
defined O
population O
was O
1 B-STAT
per I-STAT
2120 I-STAT
live I-STAT
births I-STAT
( O
47.2/100 B-STAT
000 O
; O
95 O
% O
confidence O
interval O
36.9 O
- O
57.5 O
) O
. O
PRRT2 O
was O
the O
most O
common O
single O
- O
gene O
epilepsy O
with O
an O
incidence B-EPI
of O
1 B-STAT
per I-STAT
9970 I-STAT
live I-STAT
births I-STAT
( O
10.0/100 B-STAT
000 O
; O
95 O
% O
confidence O
interval O
5.26 O
- O
14.8 O
) O
followed O
by O
SCN1A O
: O
1 B-STAT
per I-STAT
12 I-STAT
200 B-STAT
( I-STAT
8.26/100 I-STAT
000 I-STAT
; O
95 O
% O
confidence O
interval O
3.93 O
- O
12.6 O
) O
; O
KCNQ2 O
: O
1 B-STAT
per I-STAT
17 I-STAT
000 B-STAT
( I-STAT
5.89/100 I-STAT
000 I-STAT
; O
95 O
% O
confidence O
interval O
2.24 O
- O
9.56 O
) O
and O
SLC2A1 O
: O
1 B-STAT
per I-STAT
24 I-STAT
300 B-STAT
( I-STAT
4.13/100 I-STAT
000 I-STAT
; O
95 O
% O
confidence O
interval O
1.07 O
- O
7.19 O
) O
. O
Presentation O
before O
the O
age O
of O
6 O
months O
, O
and O
presentation O
with O
afebrile O
focal O
seizures O
were O
significantly O
associated O
with O
genetic O
diagnosis O
. O
Single O
- O
gene O
disorders O
accounted O
for O
a O
quarter O
of O
the O
seizure O
disorders O
in O
this O
cohort O
. O
Genetic O
testing O
is O
recommended O
to O
identify O
children O
who O
may O
benefit O
from O
precision O
treatment O
and O
should O
be O
mainstream O
practice O
in O
early O
childhood O
onset O
epilepsy O
. O
Methods O
: O
We O
analyzed O
high O
- O
resolution O
CT O
( O
HRCT O
) O
findings O
from O
six O
male O
patients O
( O
mean O
age O
, O
22.6 O
years O
) O
with O
confirmed O
diagnoses O
of O
acute O
Q O
fever O
. O
Two O
chest O
radiologists O
analyzed O
the O
images O
and O
reached O
decisions O
by O
consensus O
. O
All O
patients O
presented O
fever O
, O
myalgia O
, O
prostation O
, O
headache O
, O
and O
dry O
cough O
. O
They O
also O
had O
common O
epidemiologic O
factors O
( O
recent O
travel O
for O
military O
service O
, O
where O
they O
had O
contact O
with O
sheep O
and O
capybara O
) O
. O
Diagnoses O
were O
confirmed O
by O
the O
detection O
of O
C. O
burnetii O
DNA O
in O
clinical O
samples O
by O
polymerase O
chain O
reaction O
. O
Results O
: O
The O
predominant O
HRCT O
findings O
were O
areas O
of O
consolidation O
( O
100 O
% O
) O
and O
nodules O
( O
66.6 O
% O
) O
with O
halos O
of O
ground O
- O
glass O
opacity O
, O
predominantly O
with O
segmental O
and O
peripheral O
distributions O
. O
Lesions O
affected O
all O
lobes O
, O
and O
predominated O
in O
the O
left O
upper O
and O
lower O
lobes O
. O
Involvement O
of O
more O
than O
one O
lobe O
was O
observed O
in O
four O
patients O
. O
No O
pleural O
effusion O
or O
lymph O
node O
enlargement O
was O
found O
. O
Conclusion O
: O
The O
predominant O
HRCT O
findings O
in O
patients O
with O
acute O
Q O
fever O
pneumonia O
were O
bilateral O
, O
peripheral O
areas O
of O
consolidation O
and O
nodules O
with O
irregular O
contours O
and O
halos O
of O
ground O
- O
glass O
opacity O
. O
Advances O
in O
knowledge O
: O
Acute O
Q O
fever O
should O
be O
included O
in O
the O
differential O
diagnosis O
of O
lesions O
with O
the O
halo O
sign O
on O
HRCT O
. O
Although O
AOA1 O
( O
ataxia O
oculomotor O
apraxia1 O
) O
is O
one O
of O
the O
most O
common O
causes O
of O
autosomal O
recessive O
cerebellar O
ataxias O
in O
Japanese O
population O
, O
it O
is O
reported O
from O
all O
over O
the O
world O
. O
The O
clinical O
manifestations O
are O
similar O
to O
ataxia O
telangiectasia O
in O
which O
non O
- O
neurological O
manifestations O
are O
absent O
and O
include O
almost O
10 O
% O
of O
autosomal O
recessive O
cerebellar O
ataxias O
. O
Dysarthria O
and O
gait O
disorder O
are O
the O
most O
two O
common O
and O
typical O
manifestations O
. O
Oculomotor O
apraxia O
is O
usually O
seen O
a O
few O
years O
after O
the O
manifestations O
start O
. O
APTX O
gene O
on O
9p13.3 O
chromosome O
is O
expressed O
in O
the O
cells O
of O
all O
human O
body O
tissues O
and O
different O
mutations O
had O
been O
discovered O
. O
Here O
we O
report O
two O
siblings O
( O
a O
girl O
and O
a O
boy O
) O
of O
consanguineous O
parents O
visited O
at O
Mofid O
Pediatrics O
Hospital O
in O
2015 O
, O
with O
history O
of O
gait O
ataxia O
, O
titubation O
, O
tremor O
, O
and O
oculomotor O
apraxia O
around O
five O
yr O
old O
and O
after O
that O
. O
The O
brother O
showed O
symptoms O
of O
disease O
earlier O
and O
more O
severe O
than O
his O
sister O
did O
. O
After O
ruling O
out O
the O
common O
etiologies O
of O
progressive O
ataxia O
, O
we O
did O
genetic O
study O
for O
AOA1 O
that O
showed O
a O
homozygous O
frameshift O
mutation O
as O
c.418_418 O
del O
was O
found O
. O
This O
mutation O
was O
not O
reported O
before O
so O
this O
was O
a O
new O
mutation O
in O
APTX O
gene O
. O
In O
this O
study O
analysis O
of O
soil O
, O
water O
and O
plant O
residue O
samples O
is O
presented O
to O
evaluate O
the O
contamination O
levels O
and O
possible O
health O
risks O
. O
Hexachlorocyclohexane O
( O
HCH O
) O
is O
a O
persistent O
organic O
pollutant O
used O
as O
a O
pesticide O
in O
agricultural O
sector O
for O
pest O
control O
in O
order O
to O
obtain O
higher O
productivity O
. O
For O
analysis O
soil O
, O
water O
and O
crop O
residue O
samples O
were O
collected O
from O
different O
agricultural O
areas O
of O
the O
northern O
Punjab B-LOC
region O
of O
Pakistan B-LOC
. O
The O
investigation O
of O
the O
samples O
shows O
significant O
levels O
of O
HCH O
residues O
in O
all O
types O
of O
samples O
. O
Gas O
chromatography O
- O
mass O
spectrometry O
analysis O
was O
used O
to O
assess O
the O
higher O
residue O
levels O
of O
HCH O
in O
the O
samples O
. O
The O
concentration O
of O
HCH O
residues O
detected O
in O
samples O
ranged O
from O
2.43 O
to O
8.88 O
µg O
/ O
g O
in O
soil O
, O
nd O
-5.87 O
µg O
/ O
l O
in O
water O
and O
nd O
- O
4.87 O
µg O
/ O
g O
in O
plants O
. O
The O
presence O
of O
HCH O
residues O
in O
soil O
, O
water O
and O
plant O
samples O
was O
beyond O
the O
recommended O
quality O
guidelines O
. O
Human O
health O
risk O
was O
evaluated O
for O
cancer O
and O
non O
- O
cancer O
risks O
through O
dietary O
and O
non O
- O
dietary O
exposure O
routes O
. O
The O
hazard O
index O
was O
HI O
> B-STAT
1 I-STAT
in I-STAT
children I-STAT
and O
HI O
< O
1 O
in O
adults O
, O
while O
the O
non O
- O
dietary O
incremental O
lifetime O
cancer O
risks O
( O
ILCR O
) O
were O
beyond O
the O
internationally O
acceptable O
limit O
of O
1 O
× O
10 O
-5 O
. O
Hence O
, O
results O
of O
the O
present O
investigation O
concluded O
the O
presence O
of O
high O
levels O
of O
HCH O
residues O
in O
samples O
and O
pose O
high O
health O
risk O
to O
the O
inhabitants O
. O
These O
findings O
are O
alarming O
and O
apprise O
the O
concerned O
departments O
for O
the O
remediation O
of O
contamination O
and O
proper O
implementation O
of O
environmental O
laws O
in O
the O
area O
. O
The O
sexually O
transmitted O
enteric O
infections O
topic O
is O
one O
of O
the O
chapters O
of O
the O
Clinical O
Protocol O
and O
Therapeutic O
Guidelines O
for O
Comprehensive O
Care O
for O
People O
with O
Sexually O
Transmitted O
Infections O
, O
published O
by O
the O
Brazilian O
Ministry O
of O
Health O
in O
2020 O
. O
The O
document O
was O
developed O
based O
on O
scientific O
evidence O
and O
validated O
in O
discussions O
with O
specialists O
. O
This O
article O
presents O
epidemiological O
and O
clinical O
aspects O
of O
these O
infections O
and O
guidance O
for O
service O
managers O
on O
their O
programmatic O
and O
operational O
management O
. O
The O
aim O
is O
to O
assist O
health O
professionals O
with O
screening O
, O
diagnosis O
, O
and O
treatment O
of O
people O
with O
sexually O
transmitted O
enteric O
infections O
and O
their O
sexual O
partners O
, O
in O
addition O
to O
supporting O
strategies O
for O
their O
surveillance O
, O
prevention O
, O
and O
control O
. O
The O
incidence B-EPI
of O
anorectal O
sexually O
transmitted O
infections O
has O
increased O
over O
the O
last O
years O
, O
mainly O
due O
to O
the O
increase O
in O
the O
practice O
of O
unprotected O
receptive O
anal O
sexual O
intercourse O
. O
Bernard O
- O
Soulier O
syndrome O
is O
a O
rare O
autosomal O
recessive O
bleeding O
disorder O
and O
has O
a O
low O
incidence B-EPI
. O
Bernard O
- O
Soulier O
syndrome O
is O
caused O
by O
the O
deficiency O
of O
glycoprotein O
GPIb O
- O
V O
- O
IX O
complex O
, O
a O
receptor O
for O
von O
Willebrand O
factor O
and O
is O
characterized O
by O
thrombocytopenia O
, O
giant O
platelets O
and O
bleeding O
tendency O
. O
We O
are O
reporting O
three O
members O
of O
a O
same O
family O
with O
variable O
phenotypic O
clinical O
presentation O
. O
The O
index O
case O
is O
a O
20 O
- O
year O
- O
old O
boy O
who O
has O
a O
frequent O
presentation O
with O
epistaxis O
, O
and O
low O
platelet O
counts O
( O
25 O
× O
109 O
/ O
l O
) O
. O
He O
had O
been O
hospitalized O
multiple O
times O
and O
received O
platelet O
transfusions O
. O
His O
brother O
and O
cousin O
reported O
bleeding O
symptoms O
with O
less O
frequent O
medical O
intervention O
. O
Genetic O
analysis O
by O
next O
- O
generation O
sequencing O
identified O
a O
homozygous O
GP1BB O
variant O
( O
c.423C O
> O
A O
:p O
. O
Cys141Ter O
) O
, O
which O
segregated O
amongst O
the O
family O
members O
. O
The O
results O
led O
us O
to O
an O
improved O
insight O
into O
the O
disease O
for O
this O
family O
with O
variable O
phenotypic O
expression O
, O
in O
addition O
to O
the O
identification O
of O
a O
variant O
for O
further O
structural O
and O
functional O
characterization O
. O
Background O
: O
Thyroid O
cancer O
is O
a O
common O
malignancy O
whose O
detection O
has O
increased O
significantly O
in O
past O
decades O
. O
Most O
of O
the O
increased O
incidence B-EPI
is O
due O
to O
detection O
of O
early O
well O
- O
differentiated O
thyroid O
cancer O
, O
but O
the O
incidence B-EPI
of O
more O
advanced O
thyroid O
cancers O
has O
increased O
as O
well O
. O
Recent O
methodological O
advancements O
have O
allowed O
for O
a O
deep O
understanding O
of O
the O
molecular O
underpinnings O
of O
the O
various O
types O
of O
thyroid O
cancer O
. O
Summary O
: O
Thyroid O
cancers O
harbor O
a O
high O
frequency O
of O
potential O
druggable O
molecular O
alterations O
, O
including O
the O
highest O
frequency O
of O
oncogenic O
driver O
kinase O
fusions O
seen O
across O
all O
solid O
tumors O
. O
Analyses O
of O
poorly O
differentiated O
and O
anaplastic O
thyroid O
carcinoma O
confirmed O
that O
these O
tumors O
develop O
from O
more O
well O
- O
differentiated O
follicular O
- O
derived O
thyroid O
cancers O
through O
acquired O
additional O
mutations O
. O
The O
recognition O
of O
driver O
genomic O
alterations O
in O
thyroid O
cancers O
not O
only O
predicts O
tumor O
phenotype O
but O
also O
now O
can O
inform O
treatment O
approaches O
. O
Conclusions O
: O
Major O
progress O
in O
understanding O
the O
oncogenic O
molecular O
underpinnings O
across O
the O
array O
of O
thyroid O
cancers O
has O
led O
to O
considerable O
gains O
in O
gene O
- O
specific O
systemic O
therapies O
for O
many O
cancers O
. O
This O
article O
focuses O
on O
the O
molecular O
characteristics O
of O
aggressive O
follicular O
- O
derived O
thyroid O
cancers O
and O
medullary O
thyroid O
cancer O
and O
highlights O
advancements O
in O
treating O
thyroid O
cancer O
in O
the O
era O
of O
targeted O
therapy O
. O
Objective O
Renal O
tubular O
acidosis O
( O
RTA O
) O
is O
a O
clinical O
manifestation O
that O
occurs B-EPI
with O
insufficiency O
in O
restoring O
bicarbonate O
or O
disruption O
in O
hydrogen O
ion O
elimination O
as O
a O
result O
of O
a O
disruption O
in O
tubulus O
functions O
, O
causing O
normal O
anion O
gap O
- O
opening O
metabolic O
acidosis O
. O
In O
the O
present O
study O
, O
we O
aimed O
to O
investigate O
the O
prevalence B-EPI
of O
RTA O
in O
the O
largest O
systemic O
lupus O
erythematosus O
( O
SLE O
) O
patient O
population O
to O
date O
. O
Materials O
and O
methods O
SLE O
patients O
, O
who O
were O
followed O
up O
in O
2 O
different O
healthcare O
centers O
, O
were O
included O
. O
Patients O
with O
metabolic O
acidosis O
( O
pH O
< O
7.35 O
and O
HCO3 O
< O
22 O
mEq O
/ O
L O
) O
in O
venous O
blood O
gas O
analysis O
were O
determined O
. O
The O
serum O
and O
urine O
anion O
GAP O
of O
these O
patients O
were O
estimated O
, O
and O
the O
urine O
pH O
was O
assessed O
. O
RTA O
presence O
was O
evaluated O
as O
metabolic O
acidosis O
with O
a O
normal O
serum O
anion O
gap O
and O
a O
positive O
urine O
anion O
GAP O
. O
Results O
A O
total O
of O
108 O
patients O
were O
included O
in O
the O
present O
study O
. O
The O
mean O
age O
of O
the O
patients O
was O
41.5 O
± O
1.2 O
and O
87 O
% O
were O
female O
. O
The O
SLE O
diagnosis O
duration O
was O
75 O
± O
5 O
months O
. O
The O
mean O
creatinine O
value O
was O
0.6 O
± O
0.1 O
mg O
/ O
dL O
and O
the O
mean O
eGFR O
was O
111 O
± O
2 O
mL O
/ O
min O
. O
According O
to O
the O
blood O
gas O
analysis O
, O
18 O
patients O
( O
16.7 O
% O
of O
the O
total O
) O
had O
RTA O
. O
Sixteen O
of O
these O
patients O
had O
type O
1 B-STAT
RTA I-STAT
and I-STAT
2 I-STAT
had O
type O
2 O
RTA O
; O
type O
4 O
RTA O
was O
not O
determined O
in O
any O
of O
the O
patients O
. O
Conclusion O
RTA O
should O
be O
considered O
in O
SLE O
patients O
even O
if O
they O
have O
normal O
eGFR O
values O
. O
This O
is O
the O
largest O
study O
to O
examine O
the O
prevalence B-EPI
of O
RTA O
in O
SLE O
patients O
in O
the O
literature O
. O
Syndactyly O
and O
polydactyly O
- O
respectively O
characterized O
by O
fused O
and O
supernumerary O
digits O
- O
are O
among O
the O
most O
common O
congenital O
limb O
malformations O
, O
with O
syndactyly O
presenting O
at O
an O
estimated B-EPI
incidence I-EPI
of O
1 O
in O
2,000 O
- O
3,000 O
live O
births O
and O
polydactyly O
at O
a O
frequency O
of O
1 B-STAT
in I-STAT
approximately I-STAT
700 I-STAT
- O
1,000 O
live O
births O
. O
Despite O
their O
relatively O
regular O
manifestation O
in O
the O
clinic O
, O
the O
etiologies O
of O
syndactyly O
and O
polydactyly O
remain O
poorly O
understood O
because O
of O
their O
phenotypic O
and O
genetic O
diversity O
. O
Further O
, O
even O
though O
concrete O
knowledge O
of O
genotypic O
links O
has O
been O
established O
for O
some O
variants O
of O
syndactyly O
and O
polydactyly O
, O
there O
appears O
to O
be O
no O
single O
comprehensive O
published O
summary O
of O
all O
syndromic O
and O
nonsyndromic O
syndactyly O
and O
polydactyly O
presentations O
, O
and O
there O
is O
decidedly O
no O
resource O
that O
maps O
all O
syndromic O
and O
nonsyndromic O
syndactylies O
and O
polydactylies O
to O
their O
genetic O
bases O
. O
This O
gap O
in O
the O
literature O
problematizes O
comprehensive O
carrier O
screening O
and O
prenatal O
diagnosis O
and O
complicates O
novel O
diagnostic O
attempts O
. O
This O
review O
thus O
attempts O
to O
collect O
all O
that O
is O
known O
about O
the O
genetic O
bases O
of O
syndromic O
and O
nonsyndromic O
syndactylies O
and O
polydactylies O
, O
as O
well O
as O
to O
highlight O
the O
dactyly O
manifestations O
for O
which O
no O
genetic O
bases O
are O
as O
yet O
known O
. O
Then O
, O
having O
established O
a O
summation O
of O
existing O
and O
missing O
knowledge O
, O
this O
work O
briefly O
outlines O
the O
diagnostic O
techniques O
that O
a O
genetics O
- O
reinforced O
understanding O
of O
syndactyly O
and O
polydactyly O
could O
inform O
. O
Little O
information O
is O
available O
on O
the O
prevalences B-EPI
of O
birth O
defects O
in O
Korea B-LOC
. O
The O
aims O
of O
this O
study O
were O
to O
estimate O
recent O
prevalences B-EPI
of O
selected O
birth O
defects O
and O
to O
analyze O
the O
prevalence B-EPI
trends O
of O
these O
defects O
during O
the O
period O
from O
2008 O
to O
2014 O
. O
Prevalences B-EPI
were O
calculated O
for O
69 O
major O
birth O
defects O
using O
health O
insurance O
claim O
data O
obtained O
from O
the O
Korea O
National O
Health O
Insurance O
Service O
( O
NHIS O
) O
. O
Prevalence B-EPI
rate O
ratios O
were O
calculated O
using O
Poisson O
regression O
to O
analyze O
trends O
over O
the O
7 O
- O
year O
study O
period O
. O
The O
overall B-EPI
prevalence I-EPI
of O
a O
major O
birth O
defect O
was O
446.3 B-STAT
per I-STAT
10,000 I-STAT
births I-STAT
( O
95 O
% O
CI O
: O
444.0⁻448.6 O
) O
; O
470.9 B-STAT
per I-STAT
10,000 I-STAT
births I-STAT
( O
95 O
% O
CI O
: O
467.6⁻474.2 O
) O
for O
males O
and O
420.2 B-STAT
per I-STAT
10,000 I-STAT
births I-STAT
( O
95 O
% O
CI O
: O
417⁻423.4 O
) O
for O
females O
. O
The O
prevalence B-EPI
rates O
of O
the O
most O
common O
birth O
defects O
over O
the O
study O
period O
were O
; O
septal O
defect O
( O
138.2 B-STAT
per I-STAT
10,000 I-STAT
; O
95 O
% O
CI O
: O
136.9⁻139.5 O
) O
, O
congenital O
hip O
dislocation O
( O
652 B-STAT
per I-STAT
10,000 I-STAT
; O
95 O
% O
CI O
: O
64.1⁻65.9 O
) O
, O
and O
ventricular O
septal O
defect O
( O
62.62 B-STAT
per I-STAT
10,000 I-STAT
; O
95 O
% O
CI O
: O
61.7⁻63.5 O
) O
. O
During O
the O
study O
period O
, O
a O
significant O
increase O
in O
the O
prevalence B-EPI
of O
a O
major O
birth O
defect O
was O
observed O
with O
a O
prevalence B-EPI
rate O
ratio O
( O
PRR O
) O
of O
1.091 O
. O
The O
strongest O
trend O
was O
observed O
for O
renal O
dysplasia O
, O
which O
had O
a O
PRR O
of O
1.275 O
( O
95 O
% O
CI O
: O
1.211⁻1.343 O
) O
, O
and O
upward O
trends O
were O
observed O
for O
urogenital O
anomalies O
, O
such O
as O
, O
renal O
agenesis O
( O
PRR O
1.102 O
, O
95 O
% O
CI O
: O
1.067⁻1.138 O
) O
, O
undescended O
testis O
( O
PRR O
1.082 O
, O
95 O
% O
CI O
: O
1.072⁻1.093 O
) O
and O
hypospadias O
( O
PRR O
1.067 O
, O
95 O
% O
CI O
: O
1.044⁻1.090 O
) O
. O
This O
study O
shows O
an O
overall O
increase O
in O
the O
prevalences B-EPI
of O
birth O
defects O
, O
including O
hypospadias O
and O
undescended O
testis O
, O
which O
are O
known O
to O
be O
associated O
with O
endocrine O
factors O
. O
In O
the O
future O
, O
standardized O
birth O
defect O
registries O
should O
be O
established O
to O
enable O
these O
trends O
to O
be O
monitored O
. O
Holoprosencephaly O
is O
a O
rare O
spectrum O
of O
congenital O
malformation O
associated O
with O
midline O
facial O
defects O
and O
absence O
of O
olfactory O
tract O
. O
Sequence O
occurs B-EPI
at O
4th O
to O
8th O
week O
of O
gestational O
age O
due O
to O
failure O
or O
incomplete O
diverticulation O
and O
cleavage O
of O
primitive O
prosencephalon O
. O
It O
is O
most O
common O
brain O
malformation O
with O
an O
incidence B-EPI
1:250 O
in O
conceptuses O
and O
associated O
with O
a O
high O
rate O
of O
spontaneous O
abortion O
, O
and O
prevalence B-EPI
of O
1:16000 B-STAT
in O
live O
borns O
. O
The O
etiopathogenesis O
of O
holoprosencephaly O
is O
heterogeneous O
and O
multifactorial O
, O
may O
be O
environmental O
, O
metabolic O
factors O
or O
teratogenic O
including O
insulin O
- O
dependent O
maternal O
diabetes O
, O
alcohol O
consumption O
. O
In O
this O
study O
, O
we O
described O
a O
case O
of O
holoprosencephaly O
neonate O
with O
34 O
weeks O
gestational O
age O
and O
antenatal O
ultrasonography O
diagnosed O
as O
congenital O
defects O
in O
the O
central O
nervous O
system O
, O
asymmetric O
growth O
of O
head O
. O
After O
birth O
the O
infant O
was O
presented O
with O
multiple O
congenital O
anomalies O
( O
cleft O
lip O
, O
cleft O
palate O
, O
microphthalmia O
, O
absent O
philtrum O
, O
absent O
nasal O
septum O
with O
single O
naris O
) O
similar O
to O
holoprosencephaly O
sequence O
. O
Objectives O
Neonatal O
herpes O
simplex O
virus O
( O
HSV O
) O
infections O
are O
associated O
with O
high O
mortality O
and O
long O
- O
term O
morbidity O
. O
However O
, O
incidence B-EPI
is O
low O
and O
acyclovir O
, O
the O
treatment O
of O
choice O
, O
carries O
risk O
of O
toxicity O
. O
We O
aimed O
to O
increase O
the O
percentage O
of O
patients O
0 O
to O
60 O
days O
of O
age O
who O
are O
tested O
and O
treated O
for O
HSV O
in O
accordance O
with O
local O
guideline O
recommendations O
from O
40 O
% O
to O
80 O
% I-STAT
. O
Methods O
This O
quality O
improvement O
project O
took O
place O
at O
1 O
freestanding O
children O
's O
hospital O
. O
Multiple O
plan O
- O
do O
- O
study O
- O
act O
cycles O
were O
focused O
on O
interventions O
aimed O
at O
key O
drivers O
including O
provider O
buy O
- O
in O
, O
guideline O
availability O
, O
and O
accurate O
identification O
of O
high O
- O
risk O
patients O
. O
A O
run O
chart O
was O
used O
to O
track O
the O
effect O
of O
interventions O
on O
the O
percentage O
managed O
per O
guideline O
recommendations O
over O
time O
by O
using O
established O
rules O
for O
determining O
special O
cause O
. O
Pre- O
and O
postimplementation O
acyclovir O
use O
was O
compared O
by O
using O
a O
χ O
2 O
test O
. O
In O
HSV O
- O
positive O
cases O
, O
delayed O
acyclovir O
initiation O
, O
defined O
as O
> O
1 O
day O
from O
presentation O
, O
was O
tracked O
as O
a O
balancing O
measure O
. O
Results O
The O
median O
percentage O
of O
patients O
managed O
according O
to O
guideline O
recommendations O
increased O
from O
40 O
% O
to O
80 O
% O
within O
8 O
months O
. O
Acyclovir O
use O
decreased O
from O
26 O
% O
to O
7.9 O
% O
( O
P O
< O
.001 O
) O
in O
non O
- O
high O
- O
risk O
patients O
but O
did O
not O
change O
significantly O
in O
high O
- O
risk O
patients O
( O
73%-83 O
% O
; O
P O
= O
.15 O
) O
. O
There O
were O
no O
cases O
of O
delayed O
acyclovir O
initiation O
in O
HSV O
- O
positive O
cases O
. O
Conclusions O
Point O
- O
of O
- O
care O
availability O
of O
an O
evidence O
- O
based O
guideline O
and O
interventions O
targeted O
at O
provider O
engagement O
improved O
adherence O
to O
a O
new O
guideline O
for O
neonatal O
HSV O
management O
and O
decreased O
acyclovir O
use O
in O
non O
- O
high O
- O
risk O
infants O
. O
Further O
study O
is O
necessary O
to O
confirm O
the O
safety O
of O
these O
recommendations O
in O
other O
settings O
. O
Deficiency O
of O
hypoxanthine O
- O
guanine O
phosphoribosyltransferase O
( O
HPRT O
) O
activity O
is O
an O
inborn O
error O
of O
purine O
metabolism O
associated O
with O
uric O
acid O
overproduction O
and O
a O
continuum O
spectrum O
of O
neurological O
manifestations O
depending O
on O
the O
degree O
of O
the O
enzymatic O
deficiency O
. O
The O
prevalence B-EPI
is O
estimated O
at O
1/380,000 B-STAT
live I-STAT
births I-STAT
in O
Canada B-LOC
, O
and O
1/235,000 B-STAT
live I-STAT
births I-STAT
in O
Spain B-LOC
. O
Uric O
acid O
overproduction O
is O
present O
inall O
HPRT O
- O
deficient O
patients O
and O
is O
associated O
with O
lithiasis O
and O
gout O
. O
Neurological O
manifestations O
include O
severe O
action O
dystonia O
, O
choreoathetosis O
, O
ballismus O
, O
cognitive O
and O
attention O
deficit O
, O
and O
self O
- O
injurious O
behaviour O
. O
The O
most O
severe O
forms O
are O
known O
as O
Lesch O
- O
Nyhan O
syndrome O
( O
patients O
are O
normal O
at O
birth O
and O
diagnosis O
can O
be O
accomplished O
when O
psychomotor O
delay O
becomes O
apparent O
) O
. O
Partial O
HPRT O
- O
deficient O
patients O
present O
these O
symptoms O
with O
a O
different O
intensity O
, O
and O
in O
the O
least O
severe O
forms O
symptoms O
may O
be O
unapparent O
. O
Megaloblastic O
anaemia O
is O
also O
associated O
with O
the O
disease O
. O
Inheritance O
of O
HPRT O
deficiency O
is O
X O
- O
linked O
recessive O
, O
thus O
males O
are O
generally O
affected O
and O
heterozygous O
female O
are O
carriers O
( O
usually O
asymptomatic O
) O
. O
Human O
HPRT O
is O
encoded O
by O
a O
single O
structural O
gene O
on O
the O
long O
arm O
of O
the O
X O
chromosome O
at O
Xq26 O
. O
To O
date O
, O
more O
than O
300 O
disease O
- O
associated O
mutations O
in O
the O
HPRT1 O
gene O
have O
been O
identified O
. O
The O
diagnosis O
is O
based O
on O
clinical O
and O
biochemical O
findings O
( O
hyperuricemia O
and O
hyperuricosuria O
associated O
with O
psychomotor O
delay O
) O
, O
and O
enzymatic O
( O
HPRT O
activity O
determination O
in O
haemolysate O
, O
intact O
erythrocytes O
or O
fibroblasts O
) O
and O
molecular O
tests O
. O
Molecular O
diagnosis O
allows O
faster O
and O
more O
accurate O
carrier O
and O
prenatal O
diagnosis O
. O
Prenatal O
diagnosis O
can O
be O
performed O
with O
amniotic O
cells O
obtained O
by O
amniocentesis O
at O
about O
15 O
- O
18 O
weeks O
' O
gestation O
, O
or O
chorionic O
villus O
cells O
obtained O
at O
about O
10 O
- O
12 O
weeks O
' O
gestation O
. O
Uric O
acid O
overproduction O
can O
be O
managed O
by O
allopurinol O
treatment O
. O
Doses O
must O
be O
carefully O
adjusted O
to O
avoid O
xanthine O
lithiasis O
. O
The O
lack O
of O
precise O
understanding O
of O
the O
neurological O
dysfunction O
has O
precluded O
development O
of O
useful O
therapies O
. O
Spasticity B-LOC
, O
when O
present O
, O
and O
dystonia O
can O
be O
managed O
with O
benzodiazepines O
and O
gamma O
- O
aminobutyric O
acid O
inhibitors O
such O
as O
baclofen O
. O
Physical O
rehabilitation O
, O
including O
management O
of O
dysarthria O
and O
dysphagia O
, O
special O
devices O
to O
enable O
hand O
control O
, O
appropriate O
walking O
aids O
, O
and O
a O
programme O
of O
posture O
management O
to O
prevent O
deformities O
are O
recommended O
. O
Self O
- O
injurious O
behaviour O
must O
be O
managed O
by O
a O
combination O
of O
physical O
restraints O
, O
behavioural O
and O
pharmaceutical O
treatments O
. O
Background O
The O
state O
of O
newborn O
screening O
( O
NBS O
) O
programmes O
for O
organic O
acidurias O
in O
Europe B-LOC
was O
assessed O
by O
a O
web O
- O
based O
questionnaire O
in O
the O
EU O
programme O
of O
Community O
Action O
in O
Public O
Health O
2010/2011 O
among O
the O
- O
at O
that O
time O
- O
27 O
EU O
member O
states O
, O
candidate O
countries O
, O
potential O
candidates O
and O
three O
EFTA O
countries O
. O
Results O
Thirty O
- O
seven O
data O
sets O
from O
39 O
target O
countries O
were O
analysed O
. O
Newborn O
screening O
for O
glutaric O
aciduria O
type O
I O
( O
GA O
- O
I O
) O
was O
performed O
in O
ten O
, O
for O
isovaleric O
aciduria O
( O
IVA O
) O
in O
nine O
and O
for O
methylmalonic O
aciduria O
including O
cblA O
, O
cblB O
, O
cblC O
and O
cblD O
( O
MMACBL O
) O
as O
well O
as O
for O
propionic O
aciduria O
( O
PA O
) O
in O
seven O
countries O
. O
Samples O
were O
obtained O
at O
a O
median O
age O
of O
2.5 O
days O
and O
laboratory O
analysis O
began O
at O
median O
age O
of O
4.5 O
days O
. O
Positive O
screening O
results O
were O
mostly O
confirmed O
in O
specialised O
centres O
by O
analysis O
of O
organic O
acids O
in O
urine O
. O
Confirmation O
of O
a O
positive O
screening O
result O
usually O
did O
not O
start O
before O
the O
second O
week O
of O
life O
( O
median O
ages O
: O
9.5 O
days O
[ O
IVA O
] O
, O
9 O
days O
[ O
GA O
- O
I O
] O
, O
8.5 O
days O
[ O
PA O
, O
MMACBL O
] O
) O
and O
was O
completed O
early O
in O
the O
third O
week O
of O
life O
( O
median O
ages O
: O
15 O
days O
[ O
IVA O
, O
PA O
, O
MMA O
] O
, O
14.5 O
days O
[ O
GA O
- O
I O
] O
) O
. O
Treatment O
was O
initiated O
in O
GA O
- O
I O
and O
IVA O
at O
a O
median O
age O
of O
14 O
days O
and O
in O
MMACBL B-LOC
and O
PA O
at O
a O
median O
age O
of O
15 O
days O
. O
Conclusion O
NBS O
for O
organic O
acidurias O
in O
Europe B-LOC
is O
variable O
and O
less O
often O
established O
than O
for O
amino O
acid O
disorders O
. O
While O
for O
GA O
- O
I O
its O
benefit O
has O
already O
been O
demonstrated O
, O
there O
is O
room O
for O
debate O
of O
NBS O
for O
IVA O
and O
especially O
PA O
and O
MMACBL O
. O
Background O
IgA O
nephropathy O
( O
IgAN O
) O
is O
the O
most O
common O
primary O
glomerulonephritis O
worldwide B-LOC
. O
Although O
most O
IgAN O
cases O
are O
sporadic O
, O
few O
show O
a O
familial O
aggregation O
. O
However O
, O
the O
prevalence B-EPI
and O
prognosis O
of O
IgAN O
individuals O
with O
positive O
familial O
history O
( O
FH O
) O
of O
renal O
disorders O
remains O
uncertain O
. O
To O
address O
these O
issues O
, O
we O
conducted O
a O
longitudinal O
observational O
study O
on O
a O
single O
- O
institution O
cohort O
of O
patients O
with O
biopsy O
- O
proven O
IgAN O
. O
Methods O
A O
total O
of O
467 O
IgAN O
patients O
who O
underwent O
renal O
biopsy O
during O
1994 O
to O
2019 O
were O
ascertained O
to O
have O
positive- O
or O
negative O
- O
FH O
by O
history O
taking O
and O
were O
followed O
for O
an O
average O
of O
8.9 O
years O
. O
We O
compared O
the O
clinical O
and O
pathological O
features O
of O
the O
two O
subgroups O
. O
The O
primary O
outcome O
, O
a O
composite O
of O
a O
hard O
endpoint O
( O
end O
- O
stage O
renal O
disease O
[ O
ESRD O
] O
) O
and O
surrogate O
endpoint O
( O
a O
50 O
% O
or O
more O
reduction O
in O
the O
estimated O
glomerular O
filtration O
rate O
[ O
eGFR O
] O
from O
baseline O
) O
, O
was O
evaluated O
. O
To O
estimate O
the O
risk O
for O
progression O
to O
ESRD O
, O
a O
Cox O
proportional O
hazards O
analysis O
was O
performed O
for O
a O
subset O
of O
patients O
who O
underwent O
follow O
- O
up O
for O
> O
2 O
years O
and O
had O
an O
eGFR O
> O
30 O
mL O
/ O
min/1.73 O
m O
2 O
at O
baseline O
( O
n O
= O
389 O
; O
observation O
, O
8.7 O
years O
) O
. O
Results O
Positive O
- O
FH O
subtype O
accounted O
for O
11.6 O
% O
( O
n O
= O
54 O
) O
of O
all O
IgAN O
patients O
. O
At O
baseline O
, O
there O
were O
no O
significant O
differences O
between O
the O
positive- O
and O
negative O
- O
FH O
subgroups O
regarding O
age O
, O
sex O
, O
comorbid O
disease O
, O
MEST O
- O
C O
score O
, O
observation O
period O
, O
and O
therapeutic O
interventions O
. O
However O
, O
the O
eGFR O
value O
at O
baselines O
was O
significantly O
lower O
in O
the O
positive O
- O
FH O
subgroup O
than O
in O
the O
negative O
- O
FH O
subgroup O
( O
P O
< O
0.01 O
) O
. O
On O
multivariate O
analysis O
, O
positive O
- O
FH O
emerged O
an O
independent O
determinant O
of O
poorer O
renal O
outcomes O
( O
odds O
ratio O
, O
2.31 O
; O
95 O
% O
confidence O
interval O
, O
1.10 O
- O
4.85 O
; O
P O
= O
0.03 O
) O
, O
after O
adjusting O
for O
confounding O
factors O
. O
eGFR O
at O
follow O
- O
up O
was O
significantly O
lower O
in O
the O
positive O
- O
FH O
subgroup O
than O
in O
the O
negative O
- O
FH O
subgroup O
after O
adjustment O
for O
age O
and O
observation O
period O
. O
Conclusions O
Positive O
- O
FH O
was O
found O
in O
11.6 O
% O
of O
all O
IgAN O
patients O
, O
consistent O
with O
the O
incidence B-EPI
seen O
in O
previous O
literature O
. O
A O
significantly O
lower O
eGFR O
at O
baseline O
and O
last O
follow O
- O
up O
and O
unfavorable O
renal O
outcomes O
in O
the O
positive O
- O
FH O
subgroup O
suggest O
that O
certain O
genetic O
risk O
factors O
predisposing O
to O
renal O
failure O
may O
exist O
in O
a O
fraction O
of O
our O
IgAN O
cohort O
. O
( O
331 O
words O
) O
. O
The O
human O
T O
- O
cell O
leukemia O
virus O
type O
1 O
( O
HTLV-1 O
) O
and O
type O
2 O
( O
HTLV-2 O
) O
are O
two O
pathogenic O
retroviruses O
. O
Although O
both O
viruses O
share O
a O
common O
genome O
organization O
and O
amino O
acid O
homology O
in O
common O
viral O
proteins O
, O
the O
incidence B-EPI
of O
disease O
with O
infection O
is O
distinct O
. O
Infection O
with O
HTLV-1 O
may O
result O
in O
the O
development O
of O
adult O
T O
- O
cell O
leukemia O
/ O
lymphoma O
( O
ATL O
) O
, O
an O
aggressive O
neoplastic O
disease O
, O
or O
a O
variety O
of O
immune O
- O
mediated O
/ O
inflammatory O
disorders O
such O
as O
HTLV-1 O
associated O
myelopathy O
/ O
tropical O
spastic O
paraparesis O
( O
HAM O
/ O
TSP O
) O
, O
whereas O
HTLV-2 O
is O
less O
pathogenic O
. O
Our O
studies O
focused O
on O
the O
open O
reading O
frame O
II O
encoded O
p28 O
protein O
of O
HTLV-2 O
, O
which O
has O
been O
shown O
to O
negatively O
regulate O
viral O
expression O
by O
the O
nuclear O
retention O
of O
the O
tax O
/ O
rex O
mRNA O
. O
A O
similar O
post O
- O
transcriptional O
regulatory O
function O
has O
been O
observed O
with O
HTLV-1 O
ORF O
- O
II O
p30 O
. O
However O
, O
p28 O
contrasts O
p30 O
in O
that O
there O
appears O
to O
be O
no O
significant O
transcriptional O
effects O
. O
In O
Chapter O
2 O
, O
we O
examined O
the O
functional O
significance O
of O
p28 O
in O
HTLV-2 O
infection O
, O
proliferation O
, O
and O
immortalization O
of O
primary O
T O
- O
cells O
in O
culture O
, O
and O
viral O
infection O
and O
survival O
in O
a O
rabbit O
model O
of O
HTLV O
infection O
. O
We O
generated O
a O
novel O
HTLV-2 O
p28 O
termination O
clone O
( O
HTLV2Deltap28 O
) O
in O
which O
a O
stop O
codon O
had O
been O
introduced O
into O
the O
p28 O
sequence O
without O
altering O
the O
amino O
acid O
sequence O
of O
the O
overlapping O
regulatory O
proteins O
, O
Tax O
and O
Rex O
. O
In O
short O
- O
term O
proliferation O
and O
long O
- O
term O
immortalization O
coculture O
assays O
, O
HTLV2Deltap28 O
infected O
and O
immortalized O
primary O
human O
T O
- O
cells O
, O
similar O
to O
wtHTLV-2 O
. O
However O
, O
HTLV2Deltap28 O
had O
a O
lower O
capacity O
to O
establish O
persistent O
infection O
in O
rabbits O
, O
indicating O
the O
in O
vivo O
importance O
of O
HTLV-2 O
p28 O
. O
These O
results O
are O
consistent O
with O
the O
hypothesis O
that O
p28 O
repression O
of O
Tax O
and O
Rex O
- O
mediated O
viral O
gene O
expression O
allows O
infected O
cells O
to O
avoid O
immune O
recognition O
and O
elimination O
, O
or O
acts O
to O
enhance O
early O
viral O
spread O
by O
enhancing O
the O
survival O
of O
HTLV-2 O
infected O
cells O
. O
In O
Chapter O
3 O
, O
we O
generated O
and O
characterized O
various O
dual O
- O
promoter O
and O
single O
- O
promoter O
lentiviral O
expression O
vectors O
. O
Post O
- O
transduction O
, O
p28 O
protein O
was O
readily O
detected O
with O
the O
dual O
- O
promoter O
vectors O
in O
293 O
T O
cells O
but O
not O
in O
Jurkat B-LOC
T O
- O
cells O
. O
The O
differential O
p28 O
protein O
expression O
was O
found O
to O
be O
due O
to O
cell O
- O
type O
specific O
translation O
mechanisms O
. O
To O
circumvent O
this O
problem O
we O
utilized O
a O
single O
- O
promoter O
lentiviral O
vector O
that O
expresses O
p28 O
via O
the O
murine O
stem O
cell O
virus O
( O
MSCV)-promoter O
, O
which O
resulted O
in O
efficient O
p28 O
protein O
expression O
in O
both O
T O
- O
cell O
lines O
and O
primary O
human O
CD8 O
+ O
T O
- O
lymphocytes O
. O
In O
Chapter O
4 O
, O
the O
capacity O
of O
p28 O
to O
modify O
cellular O
gene O
expression O
was O
examined O
. O
In O
transient O
transfection O
studies O
, O
low O
doses O
of O
p28 O
modulated O
CRE- O
and O
NFκB O
- O
driven O
reporter O
constructs O
in O
293 O
T O
cells O
, O
suggesting O
the O
ability O
of O
p28 O
in O
modulating O
cellular O
gene O
expression O
. O
Interestingly O
, O
transduction O
of O
Jurkat O
T O
- O
cells O
with O
the O
lentiviral O
p28 O
expression O
vector O
had O
no O
significant O
effect O
on O
cellular O
proliferation O
. O
Additionally O
, O
initial O
analysis O
of O
global O
cellular O
gene O
expression O
by O
microarray O
analysis O
suggests O
that O
p28 O
results O
in O
nominal O
alterations O
in O
cellular O
gene O
expression O
. O
Collectively O
, O
data O
presented O
in O
this O
thesis O
indicates O
that O
p28 O
is O
critical O
for O
the O
establishment O
and O
survival O
of O
HTLV-2 O
, O
compatible O
with O
the O
conclusion O
that O
the O
regulation O
of O
HTLV O
gene O
expression O
is O
a O
tightly O
controlled O
and O
complex O
process O
. O
Ultimately O
, O
while O
minimal O
, O
the O
impact O
of O
p28 O
upon O
cellular O
genes O
likely O
contributes O
to O
HTLV-2 O
establishment O
of O
infection O
in O
vivo O
. O
Marfan O
syndrome O
( O
MFS O
) O
is O
a O
heritable O
connective O
tissue O
disorder O
( O
HCTD O
) O
caused O
by O
pathogenic O
variants O
in O
FBN1 O
that O
frequently O
occur O
de O
novo O
. O
Although O
individuals O
with O
somatogonadal O
mosaicisms O
have O
been O
reported O
with O
respect O
to O
MFS O
and O
other O
HCTD O
, O
the O
overall O
frequency O
of O
parental O
mosaicism O
in O
this O
pathology O
is O
unknown O
. O
In O
an O
attempt O
to O
estimate O
this O
frequency O
, O
we O
reviewed O
all O
the O
333 O
patients O
with O
a O
disease O
- O
causing O
variant O
in O
FBN1 O
. O
We O
then O
used O
direct O
sequencing O
, O
combined O
with O
High O
Resolution O
Melting O
Analysis O
, O
to O
detect O
mosaicism O
in O
their O
parents O
, O
complemented O
by O
NGS O
when O
a O
mosaicism O
was O
objectivized O
. O
We O
found O
that O
( O
1 O
) O
the O
number O
of O
apparently O
de O
novo O
events O
is O
much O
higher O
than O
the O
classically O
admitted O
number O
( O
around O
50 O
% O
of O
patients O
and O
not O
25 O
% O
as O
expected O
for O
FBN1 O
) O
and O
( O
2 B-STAT
) I-STAT
around O
5 O
% O
of O
the O
FBN1 O
disease O
- O
causing O
variants O
were O
not O
actually O
de O
novo O
as O
anticipated O
, O
but O
inherited O
in O
a O
context O
of O
somatogonadal O
mosaicisms O
revealed O
in O
parents O
from O
three O
families O
. O
High O
Resolution O
Melting O
Analysis O
and O
NGS O
were O
more O
efficient O
at O
detecting O
and O
evaluating O
the O
level O
of O
mosaicism O
compared O
to O
direct O
Sanger O
sequencing O
. O
We O
also O
investigated O
individuals O
with O
a O
causal O
variant O
in O
another O
gene O
identified O
through O
our O
O
aortic O
diseases O
genes O
O
NGS O
panel O
and O
report O
, O
for O
the O
first O
time O
, O
on O
an O
individual O
with O
a O
somatogonadal O
mosaicism O
in O
COL5A1 O
. O
Our O
study O
shows O
that O
parental O
mosaicism O
is O
not O
that O
rare O
in O
Marfan O
syndrome O
and O
should O
be O
investigated O
with O
appropriate O
methods O
given O
its O
implications O
in O
patient O
's O
management O
. O
Background O
The O
high O
incidence B-EPI
of O
aortic O
disease O
in O
subjects O
with O
congenital O
aortic O
valve O
malformations O
suggests O
a O
causative O
relationship O
between O
these O
2 O
conditions O
. O
The O
histological O
observation O
in O
aortic O
dilatation O
/ O
aneurysm O
/ O
dissection O
is O
Erdheim O
cystic O
medial O
necrosis O
( O
CMN O
) O
, O
a O
noninflammatory O
loss O
of O
smooth O
muscle O
cells O
( O
SMCs O
) O
, O
fragmentation O
of O
elastic O
fibers O
, O
and O
mucoid O
degeneration O
. O
Methods O
and O
results O
To O
examine O
whether O
apoptosis O
is O
1 O
of O
the O
mechanisms O
underlying O
CMN O
and O
aortic O
medial O
layer O
SMC O
loss O
, O
ascending O
aortic O
wall O
specimens O
from O
32 O
patients O
were O
collected O
at O
cardiothoracic O
surgery O
and O
examined O
by O
histochemical O
staining O
and O
terminal O
deoxynucleotidyl O
transferase O
- O
mediated O
deoxyuridine O
triphosphate O
nick O
end O
labeling O
. O
From O
echocardiography O
results O
, O
4 O
groups O
of O
patients O
were O
identified O
: O
bicuspid O
valve O
carriers O
with O
( O
bi O
/ O
dil O
) O
or O
without O
( O
bi/0 O
) O
aortic O
dilatation O
and O
tricuspid O
valve O
carriers O
with O
( O
tri O
/ O
dil O
) O
or O
without O
( O
tri/0 O
) O
aortic O
dilatation O
. O
Massive O
focal O
apoptosis O
was O
observed O
in O
the O
medial O
layers O
of O
bi O
/ O
dil O
( O
mean O
apoptotic O
index O
[ O
mAI O
] O
, O
8.1+/-6.0 B-STAT
) O
and O
tri O
/ O
dil O
( O
mAI O
, O
8.1+/-8.3 B-STAT
) O
compared O
with O
tri/0 O
( O
mAI O
, O
0.9+/-1.2 B-STAT
; O
P=0.0079 O
and O
P=0.037 O
) O
. O
In O
bi/0 B-LOC
( O
mAI O
, O
9.1+/-5.7 B-STAT
) O
compared O
with O
tri/0 O
( O
mAI O
, O
0.9+/-1.2 B-STAT
) O
, O
rates O
of O
medial O
SMC O
apoptosis O
were O
increased O
( O
P=0.0025 O
) O
. O
Bi O
/ O
dil O
( O
mean O
age O
, O
40 O
. O
6+/-15.7 B-STAT
years O
) O
were O
significantly O
younger O
than O
tri O
/ O
dil O
( O
mean O
age O
, O
56.4+/-12.8 B-STAT
years O
) O
undergoing O
the O
same O
operation O
( O
P=0.0123 O
) O
. O
Conclusions O
Premature O
medial O
layer O
SMC O
apoptosis O
could O
be O
part O
of O
a O
genetic O
program O
underlying O
aortic O
disease O
in O
patients O
with O
aortic O
valve O
malformations O
. O
Inherited O
epidermolysis O
bullosa O
is O
a O
group O
of O
genetic O
diseases O
characterized O
by O
skin O
fragility O
and O
blistering O
on O
the O
skin O
and O
mucous O
membranes O
in O
response O
to O
minimal O
trauma O
. O
Epidermolysis O
bullosa O
is O
clinically O
and O
genetically O
very O
heterogeneous O
, O
being O
classified O
into O
four O
main O
types O
according O
to O
the O
layer O
of O
skin O
in O
which O
blistering O
occurs B-EPI
: O
epidermolysis O
bullosa O
simplex O
( O
intraepidermal O
) O
, O
junctional O
epidermolysis O
bullosa O
( O
within O
the O
lamina O
lucida O
of O
the O
basement O
membrane O
) O
, O
dystrophic O
epidermolysis O
bullosa O
( O
below O
the O
basement O
membrane O
) O
, O
and O
Kindler O
epidermolysis O
bullosa O
( O
mixed O
skin O
cleavage O
pattern O
) O
. O
Furthermore O
, O
epidermolysis O
bullosa O
is O
stratified O
into O
several O
subtypes O
, O
which O
consider O
the O
clinical O
characteristics O
, O
the O
distribution O
of O
the O
blisters O
, O
and O
the O
severity O
of O
cutaneous O
and O
extracutaneous O
signs O
. O
Pathogenic O
variants O
in O
at O
least O
16 O
genes O
that O
encode O
proteins O
essential O
for O
the O
integrity O
and O
adhesion O
of O
skin O
layers O
have O
already O
been O
associated O
with O
different O
subtypes O
of O
epidermolysis O
bullosa O
. O
The O
marked O
heterogeneity O
of O
the O
disease O
, O
which O
includes O
phenotypes O
with O
a O
broad O
spectrum O
of O
severity O
and O
many O
causal O
genes O
, O
hinders O
its O
classification O
and O
diagnosis O
. O
For O
this O
reason O
, O
dermatologists O
and O
geneticists O
regularly O
review O
and O
update O
the O
classification O
criteria O
. O
This O
review O
aimed O
to O
update O
the O
state O
of O
the O
art O
on O
inherited O
epidermolysis O
bullosa O
, O
with O
a O
special O
focus O
on O
the O
associated O
clinical O
and O
genetic O
aspects O
, O
presenting O
data O
from O
the O
most O
recent O
reclassification O
consensus O
, O
published O
in O
2020 O
. O
The O
aggressive O
lymphoma O
, O
extranodal O
natural O
killer O
/ O
T O
- O
cell O
lymphoma O
- O
nasal O
type O
, O
is O
strongly O
associated O
with O
Epstein O
- O
Barr O
virus O
( O
EBV O
) O
and O
is O
most O
common O
in O
Asia B-LOC
and O
in O
South B-LOC
and O
Central B-LOC
America I-LOC
. O
By O
contrast O
, O
incidence B-EPI
is O
low O
in O
the B-LOC
United I-LOC
States I-LOC
and O
Europe B-LOC
, O
where O
extranodal O
natural O
killer O
/ O
T O
- O
cell O
lymphoma O
represents O
only O
0.2%-0.4 B-STAT
% I-STAT
of O
all O
newly O
diagnosed O
non O
- O
Hodgkin O
lymphomas O
. O
At O
diagnosis O
, O
it O
is O
important O
to O
test O
for O
EBV O
DNA O
in O
plasma O
by O
polymerase O
chain O
reaction O
and O
to O
carry O
out O
positron O
emission O
tomography O
/ O
computer O
tomography O
and O
magnetic O
resonance O
imaging O
of O
the O
nasopharynx O
. O
In O
stage O
I O
/ O
II O
disease O
, O
radiotherapy O
is O
the O
most O
important O
treatment O
modality O
, O
but O
in O
high O
- O
risk O
stage O
I O
/ O
II O
disease O
( O
stage O
II O
, O
age O
> O
60 O
y O
, O
elevated O
lactate O
dehydrogenase O
, O
Eastern O
Cooperative O
Oncology O
Group O
performance O
score O
≥2 O
, O
primary O
tumor O
invasion O
) O
, O
it O
should O
be O
combined O
with O
chemotherapy O
. O
The O
most O
optimal O
responses O
are O
reached O
with O
nonmultidrug O
resistance O
- O
based O
therapy O
( O
eg O
, O
asparaginase- O
or O
platinum O
- O
based O
therapy O
) O
. O
Therapeutic O
approaches O
consist O
of O
either O
platinum O
- O
based O
concurrent O
chemoradiotherapy O
or O
sequential O
chemoradiotherapy O
. O
The O
minimum O
dose O
of O
radiotherapy O
should O
be O
50 O
- O
56 O
Gy O
. O
Treatment O
of O
stage O
III O
/ O
IV O
disease O
consists O
of O
3 O
cycles O
of O
chemotherapy O
followed O
by O
autologous O
hematopoietic O
cell O
transplantation O
. O
Allogeneic O
hematopoietic O
cell O
transplantation O
should O
only O
be O
considered O
in O
case O
of O
relapsed O
disease O
or O
after O
difficulty O
reaching O
complete O
remission O
. O
During O
treatment O
and O
follow O
- O
up O
, O
plasma O
EBV O
levels O
should O
be O
monitored O
as O
a O
marker O
of O
tumor O
load O
. O
Rifampicin O
, O
discovered O
more O
than O
50 O
years O
ago O
, O
represents O
the O
last O
novel O
class O
of O
antibiotics O
introduced O
for O
the O
first O
- O
line O
treatment O
of O
tuberculosis O
. O
Drugs O
in O
this O
class O
form O
part O
of O
a O
6 O
- O
month O
regimen O
that O
is O
ineffective O
against O
MDR O
and O
XDR O
TB O
, O
and O
incompatible O
with O
many O
antiretroviral O
drugs O
. O
Investments O
in O
R&D O
strategies O
have O
increased O
substantially O
in O
the O
last O
decades O
. O
However O
, O
the O
number O
of O
new O
drugs O
approved O
by O
drug O
regulatory O
agencies O
worldwide B-LOC
does O
not O
increase O
correspondingly O
. O
Ruthenium O
complexes O
( O
SCAR O
) O
have O
been O
tested O
in O
our O
laboratory O
and O
showed O
promising O
activity O
against O
Mycobacterium O
tuberculosis O
. O
These O
complexes O
showed O
up O
to O
150 O
times O
higher O
activity O
against O
MTB O
than O
its O
organic O
molecule O
without O
the O
metal O
( O
free O
ligand O
) O
, O
with O
low O
cytotoxicity O
and O
high O
selectivity O
. O
In O
this O
study O
, O
promising O
results O
inspired O
us O
to O
seek O
a O
better O
understanding O
of O
the O
biological O
activity O
of O
these O
complexes O
. O
The O
in O
vitro O
biological O
results O
obtained O
with O
the O
SCAR O
compounds O
were O
extremely O
promising O
, O
comparable O
to O
or O
better O
than O
those O
for O
first O
- O
line O
drugs O
and O
drugs O
in O
development O
. O
Moreover O
, O
SCAR O
1 B-STAT
and I-STAT
4 I-STAT
, O
which O
presented O
low O
acute O
toxicity O
, O
were O
assessed O
by O
Ames O
test O
, O
and O
results O
demonstrated O
absence O
of O
mutagenicity O
. O
Objective O
: O
The O
purpose O
of O
this O
meta O
- O
analysis O
of O
longitudinal O
studies O
is O
to O
determine O
the O
safety O
and O
efficacy O
of O
artesunate O
combined O
with O
other O
forms O
of O
adjunctive O
therapies O
for O
severe O
malaria O
. O
Methods O
: O
Following O
the O
PRISMA O
guidelines O
, O
we O
searched O
multiple O
databases O
with O
the O
search O
terms O
O
artesunate O
O
and O
O
adjunctive O
therapy O
O
and O
O
severe O
malaria O
O
in O
July O
2020 O
. O
If O
the O
search O
showed O
a O
randomized O
controlled O
trial O
, O
the O
study O
was O
included O
in O
this O
meta O
- O
analysis O
. O
The O
random O
- O
effects O
model O
was O
used O
to O
calculate O
the O
combined O
incidence B-EPI
rate O
and O
relative O
risk O
or O
risk O
difference O
. O
Results O
: O
This O
meta O
- O
analysis O
included O
nine O
longitudinal O
studies O
with O
724 O
participants O
. O
We O
found O
that O
the O
mortality O
rates O
in O
the O
artesunate O
monotherapy O
group O
and O
the O
artesunate O
+ O
adjuvant O
therapy O
group O
are O
similar O
( O
RD O
= O
-0.02 O
, O
95 O
% O
confidence O
interval O
: O
-0.06 O
- O
0.02 O
) O
. O
The O
incidence B-EPI
of O
adverse O
reactions O
in O
the O
artesunate O
monotherapy O
group O
and O
the O
artesunate O
+ O
adjuvant O
therapy O
group O
was O
also O
similar O
. O
Conclusion O
: O
No O
significant O
differences O
in O
safety O
and O
efficacy O
were O
observed O
between O
the O
artesunate O
monotherapy O
group O
and O
the O
artesunate O
+ O
adjuvant O
therapy O
group O
. O
Higher O
quality O
and O
rigorously O
designed O
randomized O
controlled O
studies O
are O
needed O
to O
validate O
our O
findings O
. O
Vitamin O
K O
- O
dependent O
factor O
X O
( O
FX O
) O
plays O
an O
important O
role O
in O
thrombin O
formation O
, O
and O
a O
deficiency O
in O
FX O
can O
cause O
impaired O
coagulation O
, O
the O
severity O
of O
which O
is O
usually O
correlated O
with O
the O
degree O
of O
deficiency O
. O
Due O
to O
the O
critical O
role O
that O
FX O
plays O
in O
the O
coagulation O
cascade O
, O
FX O
deficiency O
is O
associated O
with O
a O
higher O
risk O
of O
bleeding O
than O
deficiencies O
in O
other O
coagulation O
factors O
. O
Patients O
with O
the O
hereditary O
autosomal O
- O
recessive O
homozygous O
form O
of O
FX O
deficiency O
, O
which O
occurs B-EPI
in O
approximately B-STAT
1:1,000,000 I-STAT
individuals I-STAT
worldwide B-LOC
, O
are O
often O
diagnosed O
when O
they O
present O
with O
spontaneous O
life O
- O
threatening O
haemorrhage O
( O
most O
often O
intracranial O
haemorrhage O
) O
during O
the O
first O
month O
of O
life O
. O
In O
addition O
to O
central O
nervous O
system O
bleeds O
, O
other O
severe O
bleeding O
types O
experienced O
by O
such O
patients O
may O
include O
umbilical O
cord O
bleeding O
, O
gastrointestinal O
or O
pulmonary O
haemorrhage O
, O
intramuscular O
haematomas O
and/or O
haemarthrosis O
. O
Delayed O
treatment O
or O
inadequate O
replacement O
of O
FX O
may O
result O
in O
developmental O
delays O
, O
musculoskeletal O
disabilities O
or O
death O
. O
The O
high O
risk O
of O
recurrent O
severe O
bleeding O
necessitates O
prophylactic O
replacement O
therapy O
for O
many O
individuals O
with O
severe O
FX O
deficiency O
. O
Available O
products O
for O
replacement O
therapy O
include O
plasma O
- O
derived O
FX O
concentrate O
and O
prothrombin O
complex O
concentrates O
. O
Fresh O
- O
frozen O
plasma O
may O
be O
used O
when O
concentrates O
are O
not O
available O
but O
is O
a O
less O
efficient O
means O
of O
FX O
replacement O
. O
This O
article O
reviews O
the O
literature O
on O
severe O
bleeding O
in O
individuals O
with O
hereditary O
FX O
deficiency O
and O
discusses O
current O
treatment O
options O
. O
A O
series O
of O
simplex O
cases O
have O
been O
reported O
under O
various O
diagnoses O
sharing O
early O
aging O
, O
especially O
evident O
in O
congenitally O
decreased O
subcutaneous O
fat O
tissue O
and O
sparse O
hair O
, O
bone O
dysplasia O
of O
the O
skull O
and O
fingers O
, O
a O
distinctive O
facial O
gestalt O
, O
and O
prenatal O
and O
postnatal O
growth O
retardation O
. O
For O
historical O
reasons O
, O
we O
suggest O
naming O
the O
entity O
Fontaine O
syndrome O
. O
Exome O
sequencing O
of O
four O
unrelated O
affected O
individuals O
showed O
that O
all O
carried O
the O
de O
novo O
missense O
variant O
c.649C O
> O
T O
( O
p. O
Arg217Cys O
) O
or O
c.650G O
> O
A O
( O
p. O
Arg217His O
) O
in O
SLC25A24 O
, O
a O
solute O
carrier O
25 O
family O
member O
coding O
for O
calcium O
- O
binding O
mitochondrial O
carrier O
protein O
( O
SCaMC-1 O
, O
also O
known O
as O
SLC25A24 O
) O
. O
SLC25A24 O
allows O
an O
electro O
- O
neutral O
and O
reversible O
exchange O
of O
ATP O
- O
Mg O
and O
phosphate O
between O
the O
cytosol O
and O
mitochondria O
, O
which O
is O
required O
for O
maintaining O
optimal O
adenine O
nucleotide O
levels O
in O
the O
mitochondrial O
matrix O
. O
Molecular O
dynamic O
simulation O
studies O
predict O
that O
p. O
Arg217Cys O
and O
p. O
Arg217His O
narrow O
the O
substrate O
cavity O
of O
the O
protein O
and O
disrupt O
transporter O
dynamics O
. O
SLC25A24 O
- O
mutant O
fibroblasts O
and O
cells O
expressing O
p. O
Arg217Cys O
or O
p. O
Arg217His O
variants O
showed O
altered O
mitochondrial O
morphology O
, O
a O
decreased O
proliferation O
rate O
, O
increased O
mitochondrial O
membrane O
potential O
, O
and O
decreased O
ATP O
- O
linked O
mitochondrial O
oxygen O
consumption O
. O
The O
results O
suggest O
that O
the O
SLC25A24 O
mutations O
lead O
to O
impaired O
mitochondrial O
ATP O
synthesis O
and O
cause O
hyperpolarization O
and O
increased O
proton O
leak O
in O
association O
with O
an O
impaired O
energy O
metabolism O
. O
Our O
findings O
identify O
SLC25A24 O
mutations O
affecting O
codon O
217 O
as O
the O
underlying O
genetic O
cause O
of O
human O
progeroid O
Fontaine O
syndrome O
. O
Usher O
syndrome O
type O
1 O
( O
US1 O
) O
is O
an O
autosomal O
recessive O
disease O
characterized O
by O
profound O
congenital O
hearing O
impairment O
with O
unintelligible O
speech O
, O
early O
retinitis O
pigmentosa O
, O
and O
constant O
vestibular O
dysfunction O
. O
Three O
localizations O
have O
been O
described O
in O
US1 O
: O
USH1A O
, O
14q32 O
; O
USH1B O
, O
11q13.5 O
; O
and O
USH1C O
, O
11p15 O
. O
Studying O
a O
series O
of O
33 O
affected O
individuals O
belonging O
to O
20 O
US1 O
pedigrees O
of O
French O
ancestry O
, O
we O
found O
that O
none O
of O
the O
three O
localizations O
accounted O
for O
all O
US1 O
families O
in O
our O
series O
( O
Zmax O
= O
1.48 O
at O
theta O
= O
0.10 O
; O
Zmax O
= O
1.45 O
at O
theta O
= O
0.10 O
; O
and O
Zmax O
= O
0.36 O
at O
theta O
= O
0.20 O
for O
probes O
MLJ14 O
, O
Zd5 O
, O
and O
Mfd58 O
, O
respectively O
, O
at O
loci O
D14S13 O
, O
D11S527 O
, O
and O
D11S419 O
, O
respectively O
) O
. O
However O
, O
when O
our O
sample O
was O
split O
into O
two O
groups O
according O
to O
the O
geographic O
origin O
of O
the O
probands O
' O
grandparents O
, O
we O
were O
able O
to O
confirm O
the O
presence O
of O
a O
gene O
for O
US1 O
on O
chromosome O
14q32 O
( O
USH1A O
) O
in O
9 O
families O
originating O
from O
the O
Poitou B-LOC
region O
in O
Western B-LOC
France I-LOC
( O
Department O
of O
Deux O
- O
Sèvres O
; O
Zmax O
= O
4.46 O
at O
theta O
= O
0 O
for O
probe O
MLJ14 O
at O
the O
D14S13 O
locus O
, O
Morton O
likelihood O
ratio O
test O
, O
P O
< O
0.01 O
) O
. O
Moreover O
, O
we O
refined O
the O
genetic O
mapping O
of O
USH1A O
by O
showing O
that O
the O
disease O
gene O
maps O
to O
the O
D14S13 O
locus O
, O
within O
the O
genetic O
interval O
defined O
by O
loci O
D14S78 O
and O
D14S250 O
( O
location O
score O
in O
log O
base O
10 O
= O
4.90 O
) O
. O
Consistent O
with O
this O
, O
nonsignificant O
lod O
score O
values O
for O
linkage O
to O
either O
USH1B O
or O
USH1C O
were O
found O
in O
this O
group O
. O
( O
ABSTRACT O
TRUNCATED O
AT O
250 O
WORDS O
) O
Little O
information O
is O
available O
on O
the O
prevalence B-EPI
, O
geographic O
distribution O
and O
mutation O
spectrum O
of O
genetic O
skeletal O
disorders O
( O
GSDs O
) O
in O
China B-LOC
. O
This O
study O
systematically O
reviewed O
GSDs O
as O
defined O
in O
O
Nosology O
and O
Classification O
of O
genetic O
skeletal O
disorders O
( O
2010 O
version O
) O
O
using O
Chinese O
biomedical O
literature O
published O
over O
the O
past O
34 O
years O
from O
1978 O
to O
2012 O
. O
In O
total O
, O
16,099 O
GSDs O
have O
been O
reported O
. O
The O
most O
frequently O
reported O
disorders O
were O
Marfan O
syndrome O
, O
osteogenesis O
imperfecta O
, O
fibrous O
dysplasia O
, O
mucopolysaccharidosis O
, O
multiple O
cartilaginous O
exostoses O
, O
neurofibromatosis O
type O
1 O
( O
NF1 O
) O
, O
osteopetrosis O
, O
achondroplasia O
, O
enchondromatosis O
( O
Ollier O
) O
, O
and O
osteopoikilosis O
, O
accounting O
for O
76.5 O
% O
( O
12,312 O
cases O
) O
of O
the O
total O
cases O
. O
Five O
groups O
( O
group O
8 O
, O
12 O
, O
14 O
, O
18 O
, O
21 O
) O
defined O
by O
O
Nosology O
and O
Classification O
of O
genetic O
skeletal O
disorders O
O
have O
not O
been O
reported O
in O
the O
Chinese O
biomedical O
literature O
. O
Gene O
mutation O
testing O
was O
performed O
in O
only O
a O
minor O
portion O
of O
the O
16,099 O
cases O
of O
GSDs O
( O
187 O
cases O
, O
1.16 O
% O
) O
. O
In O
total O
, O
37 O
genes O
for O
41 O
different O
GSDs O
were O
reported O
in O
Chinese O
biomedical O
literature O
, O
including O
43 O
novel O
mutations O
. O
This O
review O
revealed O
a O
significant O
imbalance O
in O
rare O
disease O
identification O
in O
terms O
of O
geographic O
regions O
and O
hospital O
levels O
, O
suggesting O
the O
need O
to O
create O
a O
national O
multi O
- O
level O
network O
to O
meet O
the O
specific O
challenge O
of O
care O
for O
rare O
diseases O
in O
China B-LOC
. O
Newborn O
screening O
( O
NBS O
) O
in O
Alberta B-LOC
is O
delivered O
by O
a O
number O
of O
government O
and O
health O
service O
entities O
who O
work O
together O
to O
provide O
newborn O
screening O
to O
infants O
born O
in O
Alberta B-LOC
, O
the B-LOC
Northwest I-LOC
Territories I-LOC
, O
and O
the O
Kitikmeot B-LOC
region O
of O
the O
Nunavut O
territory O
. O
The O
Alberta B-LOC
panel O
screens O
for O
21 O
disorders O
( O
16 O
metabolic O
, O
two O
endocrine O
, O
cystic O
fibrosis O
, O
severe O
combined O
immunodeficiency O
, O
and O
sickle O
cell O
disease O
) O
. O
NBS O
is O
a O
standard O
of O
care O
, O
but O
is O
not O
mandatory O
. O
NBS O
performance O
is O
monitored O
by O
the O
Alberta O
Newborn O
Metabolic O
Screening O
( O
NMS O
) O
Program O
and O
NMS O
Laboratory O
, O
who O
strive O
for O
continuous O
quality O
improvement O
. O
Performance O
analysis O
found O
that O
over O
99 O
% O
of O
registered O
infants O
in O
Alberta B-LOC
received O
a O
newborn O
screen O
and O
over O
98 O
% O
of O
these O
infants O
received O
a O
screen O
result O
within O
10 O
days O
of O
age O
. O
To O
date O
, O
retinal O
implants O
are O
the O
only O
available O
treatment O
for O
blind O
individuals O
with O
retinal O
degenerations O
such O
as O
retinitis O
pigmentosa O
. O
Argus O
II O
is O
the O
only O
visual O
implant O
with O
FDA O
approval O
, O
with O
more O
than O
300 O
users O
worldwide B-LOC
. O
Argus O
II O
stimulation O
is O
based O
on O
a O
grayscale O
image O
coming O
from O
a O
head O
- O
mounted O
visible O
- O
light O
camera O
. O
Normally O
, O
the O
11 O
° O
×19 O
° O
field O
of O
view O
of O
the O
Argus O
II O
user O
is O
full O
of O
objects O
that O
may O
elicit O
similar O
phosphenes O
. O
The O
prosthesis O
can O
not O
meaningfully O
convey O
so O
much O
visual O
information O
, O
and O
the O
percept O
is O
reduced O
to O
an O
ambiguous O
impression O
of O
light O
. O
This O
study O
is O
aimed O
at O
investigating O
the O
efficacy O
of O
simplifying O
the O
video O
input O
in O
real O
- O
time O
using O
a O
heat O
- O
sensitive O
camera O
. O
Data O
were O
acquired O
from O
four O
Argus O
II O
users O
in O
5 O
stationary O
tasks O
with O
either O
hot O
objects O
or O
human O
targets O
as O
stimuli O
. O
All O
tasks O
were O
of O
m O
- O
alternative O
forced O
choice O
design O
where O
precisely O
one O
of O
the O
m≥2 O
response O
alternatives O
was O
defined O
to O
be O
O
correct O
O
by O
the O
experimenter O
. O
To O
compare O
performance O
with O
heat O
- O
sensitive O
and O
normal O
cameras O
across O
all O
tasks O
, O
regardless O
of O
m O
, O
we O
used O
an O
extension O
of O
signal O
detection O
theory O
to O
latent O
variables O
, O
estimating O
person O
ability O
and O
item O
difficulty O
in O
d O
' O
units O
. O
Results O
demonstrate O
that O
subject O
performance O
was O
significantly O
better O
across O
all O
tasks O
with O
the O
thermal O
camera O
compared O
to O
the O
regular O
Argus O
II O
camera O
. O
The O
future O
addition O
of O
thermal O
imaging O
to O
devices O
with O
very O
poor O
spatial O
resolution O
may O
have O
significant O
real O
- O
life O
benefits O
for O
orientation O
, O
personal O
safety O
, O
and O
social O
interactions O
, O
thereby O
improving O
quality O
of O
life O
. O
West B-LOC
Nile I-LOC
virus O
( O
WNV O
) O
is O
a O
flavivirus O
which O
transmission O
cycle O
is O
maintained O
between O
mosquitoes O
and O
birds O
, O
although O
it O
occasionally O
causes O
sporadic O
outbreaks O
in O
horses O
and O
humans O
that O
can O
result O
in O
serious O
diseases O
and O
even O
death O
. O
Since O
its O
first O
isolation O
in O
Africa B-LOC
in O
1937 O
, O
WNV O
had O
been O
considered O
a O
neglected O
pathogen O
until O
its O
recent O
spread O
throughout O
Europe B-LOC
and O
the O
colonization O
of O
America B-LOC
, O
regions O
where O
it O
continues O
to O
cause O
outbreaks O
with O
severe O
neurological O
consequences O
in O
humans O
and O
horses O
. O
Although O
our O
knowledge O
about O
the O
characteristics O
and O
consequences O
of O
the O
virus O
has O
increased O
enormously O
lately O
, O
many O
questions O
remain O
to O
be O
resolved O
. O
Here O
, O
we O
thoroughly O
update O
our O
knowledge O
of O
different O
aspects O
of O
the O
WNV O
life O
cycle O
: O
virology O
and O
molecular O
classification O
, O
host O
cell O
interactions O
, O
transmission O
dynamics O
, O
host O
range O
, O
epidemiology O
and O
surveillance O
, O
immune O
response O
, O
clinical O
presentations O
, O
pathogenesis O
, O
diagnosis O
, O
prophylaxis O
( O
antivirals O
and O
vaccines O
) O
, O
and O
prevention O
, O
and O
we O
highlight O
those O
aspects O
that O
are O
still O
unknown O
and O
that O
undoubtedly O
require O
further O
investigation O
. O
The O
global O
spread O
of O
COVID-19 O
constitutes O
the O
most O
dangerous O
pandemic O
to O
emerge O
during O
the O
last O
one O
hundred O
years O
. O
About O
seventy O
- O
nine O
million O
infections O
and O
more O
than O
1.7 O
million O
death O
have O
been O
reported O
to O
date O
, O
along O
with O
destruction O
of O
the O
global O
economy O
. O
With O
the O
uncertainty O
evolved O
by O
alarming O
level O
of O
genome O
mutations O
, O
coupled O
with O
likelihood O
of O
generating O
only O
a O
short O
lived O
immune O
response O
by O
the O
vaccine O
injections O
, O
the O
identification O
of O
antiviral O
drugs O
for O
direct O
therapy O
is O
the O
need O
of O
the O
hour O
. O
Strategies O
to O
inhibit O
virus O
infection O
and O
replication O
focus O
on O
targets O
such O
as O
the O
spike O
protein O
and O
non O
- O
structural O
proteins O
including O
the O
highly O
conserved O
RNA O
- O
dependent O
- O
RNA O
- O
polymerase O
, O
nucleotidyl O
- O
transferases O
, O
main O
protease O
and O
papain O
- O
like O
proteases O
. O
There O
is O
also O
an O
indirect O
option O
to O
target O
the O
host O
cell O
recognition O
systems O
such O
as O
angiotensin O
- O
converting O
enzyme O
2 O
( O
ACE2 O
) O
, O
transmembrane O
protease O
, O
serine O
2 O
, O
host O
cell O
expressed O
CD147 O
, O
and O
the O
host O
furin O
. O
A O
drug O
search O
strategy O
consensus O
in O
tandem O
with O
analysis O
of O
currently O
available O
information O
is O
extremely O
important O
for O
the O
rapid O
identification O
of O
anti O
- O
viral O
. O
An O
unprecedented O
display O
of O
cooperation O
among O
the O
scientific O
community O
regarding O
SARS O
- O
CoV-2 O
research O
has O
resulted O
in O
the O
accumulation O
of O
an O
enormous O
amount O
of O
literature O
that O
requires O
curation O
. O
Drug O
repurposing O
and O
drug O
combinations O
have O
drawn O
tremendous O
attention O
for O
rapid O
therapeutic O
application O
, O
while O
high O
throughput O
screening O
and O
virtual O
searches O
support O
de O
novo O
drug O
identification O
. O
Here O
, O
we O
examine O
how O
certain O
approved O
drugs O
targeting O
different O
viruses O
can O
play O
a O
role O
in O
combating O
this O
new O
virus O
and O
analyze O
how O
they O
demonstrate O
efficacy O
under O
clinical O
assessment O
. O
Suggestions O
on O
repurposing O
and O
de O
novo O
strategies O
are O
proposed O
to O
facilitate O
the O
fight O
against O
the O
COVID-19 O
pandemic O
. O
The O
oral O
- O
facial O
- O
digital O
syndrome O
type O
I O
( O
OFD O
I O
) O
is O
characterized O
by O
multiple O
congenital O
malformations O
of O
the O
face O
, O
oral O
cavity O
and O
digits O
. O
A O
polycystic O
kidney O
disease O
( O
PKD O
) O
is O
found O
in O
about O
one O
- O
third O
of O
patients O
but O
long O
- O
term O
outcome O
and O
complications O
are O
not O
well O
described O
in O
the O
international O
literature O
. O
Renal O
findings O
have O
been O
retrospectively O
collected O
in O
a O
cohort O
of O
34 O
females O
all O
carrying O
a O
pathogenic O
mutation O
in O
the O
OFD1 O
gene O
with O
ages O
ranging O
from O
1 B-STAT
to I-STAT
65 I-STAT
years O
. O
Twelve O
patients O
presented O
with O
PKD B-STAT
- I-STAT
11/16 I-STAT
( O
69 O
% O
) O
if O
only O
adults O
were O
considered O
-with O
a O
median O
age O
at O
diagnosis O
of O
29 O
years O
[ O
IQR O
( O
interquartile O
range O
) O
= O
( O
23.5 O
- O
38 O
) O
] O
. O
Among O
them O
, O
10 O
also O
presented O
with O
renal O
impairment O
and O
6 O
were O
grafted O
( O
median O
age O
= O
38 O
years O
[ O
IQR O
= O
( O
25 O
- O
48 O
) O
] O
. O
One O
grafted O
patient O
under O
immunosuppressive O
treatment O
died O
from O
a O
tumor O
originated O
from O
a O
native O
kidney O
. O
The O
probability O
to O
develop O
renal O
failure O
was O
estimated O
to O
be O
more O
than O
50 B-STAT
% O
after O
the O
age O
of O
36 O
years O
. O
Besides O
, O
neither O
genotype O
- O
phenotype O
correlation O
nor O
clinical O
predictive O
association O
with O
renal O
failure O
could O
be O
evidenced O
. O
These O
data O
reveal O
an O
unsuspected O
high O
incidence B-EPI
rate O
of O
the O
renal O
impairment O
outcome O
in O
OFD O
I O
syndrome O
. O
A O
systematic O
ultrasound O
( O
US B-LOC
) O
and O
renal O
function O
follow O
- O
up O
is O
therefore O
highly O
recommended O
for O
all O
OFD O
I O
patients O
. O
Introduction O
Limited O
data O
are O
available O
on O
the O
incidence B-EPI
of O
primary O
ophthalmic O
cancers O
worldwide B-LOC
. O
We O
describe O
the O
incidence B-EPI
and O
trends O
of O
primary O
ophthalmic O
cancers O
in O
Singapore B-LOC
. O
Methods O
Data O
on O
ophthalmic O
cancers O
diagnosed O
in O
Singapore B-LOC
from O
1996 O
to O
2016 O
were O
retrieved O
from O
the O
Singapore O
Cancer O
Registry O
for O
analysis O
. O
All O
were O
histologically O
proven O
primary O
ophthalmic O
cancers O
. O
Calculations O
of O
incidence B-EPI
and O
age O
- O
specific O
frequency O
of O
ophthalmic O
malignancy O
were O
made O
. O
Results O
A O
total O
of O
297 O
cases O
were O
included O
, O
with O
males O
constituting O
59.9 B-STAT
% I-STAT
. O
The O
race O
distribution O
was O
78.5 O
% O
Chinese O
, O
16.5 O
% O
Malay O
, O
3.7 O
% O
Indians O
and O
1.3 O
% O
others O
. O
There O
was O
an O
overall O
increase O
in O
ophthalmic O
malignancies O
. O
The O
mean O
age O
of O
onset O
was O
47.4 O
years O
. O
The O
most O
common O
cancers O
were O
retinoblastoma O
( O
93.3 O
% O
) O
in O
patients O
younger O
than O
15 O
years O
, O
and O
lymphoma O
( O
71.3 O
% O
) O
in O
patients O
aged O
15 O
years O
and O
older O
. O
There O
has O
been O
an O
increase O
in O
lymphomas O
from O
16.7 O
% O
in O
1968 O
- O
1995 O
to O
71.3 O
% O
in O
1996 O
- O
2016 O
in O
those O
aged O
15 O
years O
and O
older O
. O
The O
most O
common O
types O
of O
ophthalmic O
cancer O
according O
to O
location O
are O
lymphoma O
of O
the O
orbit O
, O
conjunctiva O
, O
cornea O
and O
lacrimal O
gland O
; O
retinoblastoma O
of O
the O
retina O
; O
and O
malignant O
melanoma O
of O
the O
choroid O
and O
ciliary O
body O
. O
Conclusion O
Our O
study O
reported O
the O
incidence B-EPI
and O
trends O
of O
ophthalmic O
cancer O
in O
the O
Singapore B-LOC
population O
and O
showed O
an O
overall O
increase O
in O
ophthalmic O
malignancies O
in O
Singapore B-LOC
from O
1996 O
- O
2016 O
. O
A O
substantial O
increase O
in O
lymphomas O
over O
the O
last O
2 O
decades O
was O
noted O
. O
The O
data O
could O
aid O
clinicians O
, O
epidemiologists O
and O
policymakers O
in O
implementing O
strategies O
to O
address O
trends O
in O
ophthalmic O
cancers O
and O
spur O
aetiological O
research O
to O
improve O
quality O
of O
life O
in O
patients O
with O
such O
cancers O
. O
Purpose O
of O
review O
Cardiovascular O
toxicity O
is O
a O
leading O
cause O
of O
mortality O
among O
cancer O
survivors O
and O
has O
become O
increasingly O
prevalent B-EPI
due O
to O
improved O
cancer O
survival O
rates O
. O
In O
this O
review O
, O
we O
synthesize O
evidence O
illustrating O
how O
common O
cancer O
therapeutic O
agents O
, O
such O
as O
anthracyclines O
, O
human O
epidermal O
growth O
factors O
receptors O
( O
HER2 O
) O
monoclonal O
antibodies O
, O
and O
tyrosine O
kinase O
inhibitors O
( O
TKIs O
) O
, O
have O
been O
evaluated O
in O
cardiomyocytes O
( O
CMs O
) O
derived O
from O
human O
- O
induced O
pluripotent O
stem O
cells O
( O
hiPSCs O
) O
to O
understand O
the O
underlying O
mechanisms O
of O
cardiovascular O
toxicity O
. O
We O
place O
this O
in O
the O
context O
of O
precision O
cardio O
- O
oncology O
, O
an O
emerging O
concept O
for O
personalizing O
the O
prevention O
and O
management O
of O
cardiovascular O
toxicities O
from O
cancer O
therapies O
, O
accounting O
for O
each O
individual O
patient O
's O
unique O
factors O
. O
We O
outline O
steps O
that O
will O
need O
to O
be O
addressed O
by O
multidisciplinary O
teams O
of O
cardiologists O
and O
oncologists O
in O
partnership O
with O
regulators O
to O
implement O
future O
applications O
of O
hiPSCs O
in O
precision O
cardio O
- O
oncology O
. O
Recent O
findings O
Current O
prevention O
of O
cardiovascular O
toxicity O
involves O
routine O
screenings O
and O
management O
of O
modifiable O
risk O
factors O
for O
cancer O
patients O
, O
as O
well O
as O
the O
initiation O
of O
cardioprotective O
medications O
. O
Despite O
recent O
advancements O
in O
precision O
cardio O
- O
oncology O
, O
knowledge O
gaps O
remain O
and O
limit O
our O
ability O
to O
appropriately O
predict O
with O
precision O
which O
patients O
will O
develop O
cardiovascular O
toxicity O
. O
Investigations O
using O
patient O
- O
specific O
CMs O
facilitate O
pharmacological O
discovery O
, O
mechanistic O
toxicity O
studies O
, O
and O
the O
identification O
of O
cardioprotective O
pathways O
. O
Studies O
with O
hiPSCs O
demonstrate O
that O
patients O
with O
comorbidities O
have O
more O
frequent O
adverse O
responses O
, O
compared O
to O
their O
counterparts O
without O
cardiac O
disease O
. O
Further O
studies O
utilizing O
hiPSC O
modeling O
should O
be O
considered O
, O
to O
evaluate O
the O
impact O
and O
mitigation O
of O
known O
cardiovascular O
risk O
factors O
, O
including O
blood O
pressure O
, O
body O
mass O
index O
( O
BMI O
) O
, O
smoking O
status O
, O
diabetes O
, O
and O
physical O
activity O
in O
their O
role O
in O
cardiovascular O
toxicity O
after O
cancer O
therapy O
. O
Future O
real O
- O
world O
applications O
will O
depend O
on O
understanding O
the O
current O
use O
of O
hiPSC O
modeling O
in O
order O
for O
oncologists O
and O
cardiologists O
together O
to O
inform O
their O
potential O
to O
improve O
our O
clinical O
collaborative O
practice O
in O
cardio O
- O
oncology O
. O
When O
applying O
such O
in O
vitro O
characterization O
, O
it O
is O
hypothesized O
that O
a O
safety O
score O
can O
be O
assigned O
to O
each O
individual O
to O
determine O
who O
has O
a O
greater O
probability O
of O
developing O
cardiovascular O
toxicity O
. O
Using O
hiPSCs O
to O
create O
personalized O
models O
and O
ultimately O
evaluate O
the O
cardiovascular O
toxicity O
of O
individuals O
' O
treatments O
may O
one O
day O
lead O
to O
more O
patient O
- O
specific O
treatment O
plans O
in O
precision O
cardio O
- O
oncology O
while O
reducing O
cardiovascular O
disease O
( O
CVD O
) O
morbidity O
and O
mortality O
. O
Background O
and O
objective O
Congenital O
adrenal O
hyperplasia O
involves O
a O
series O
of O
autosomal O
recessive O
disorders O
where O
adrenal O
steroidogenesis O
is O
affected O
. O
We O
present O
a O
detailed O
molecular O
investigation O
of O
13 O
newborns O
affected O
from O
the O
severe O
form O
of O
congenital O
adrenal O
hyperplasia O
related O
to O
21 O
- O
hydroxylase O
deficiency O
. O
Methods O
All O
patients O
were O
diagnosed O
with O
classical O
congenital O
adrenal O
hyperplasia O
in O
the O
neonatal O
period O
due O
to O
adrenal O
crisis O
and/or O
ambiguous O
genitalia O
presentation O
. O
None O
of O
the O
infants O
was O
identified O
through O
a O
congenital O
adrenal O
hyperplasia O
newborn O
screening O
program O
. O
A O
molecular O
analysis O
of O
the O
CYP21A2 O
gene O
and O
a O
familiar O
segregation O
analysis O
were O
performed O
. O
Results O
Adrenal O
crisis O
was O
the O
most O
severe O
manifestation O
in O
the O
male O
salt O
- O
wasting O
newborns O
while O
all O
female O
patients O
presented O
with O
atypical O
genitalia O
. O
Newborns O
were O
correctly O
genotyped O
and O
no O
genotype O
- O
phenotype O
divergences O
were O
found O
. O
Two O
novel O
severe O
genotypes O
, O
not O
previously O
reported O
, O
were O
identified O
. O
The O
novel O
CYP21A2 O
frameshift O
mutations O
( O
c.793delG O
and O
c.297dupG O
) O
were O
added O
to O
the O
other O
45 O
variants O
recently O
reported O
in O
the O
literature O
, O
leading O
to O
a O
total O
count O
of O
279 O
pathogenic O
variants O
affecting O
the O
gene O
. O
Conclusions O
We O
have O
successfully O
genotyped O
13 O
infants O
diagnosed O
with O
classical O
congenital O
adrenal O
hyperplasia O
after O
birth O
. O
Our O
molecular O
approach O
led O
to O
the O
identification O
of O
two O
novel O
frameshift O
CYP21A2 O
pathogenic O
variants O
related O
to O
the O
salt O
- O
wasting O
form O
of O
congenital O
adrenal O
hyperplasia O
. O
Idiopathic O
nephrotic O
syndrome O
newly O
affects O
1 B-STAT
- I-STAT
3 B-STAT
per I-STAT
100,000 I-STAT
children I-STAT
per I-STAT
year I-STAT
. O
Approximately O
85 O
% O
of O
cases O
show O
complete O
remission O
of O
proteinuria O
following O
glucocorticoid O
treatment O
. O
Patients O
who O
do O
not O
achieve O
complete O
remission O
within O
4 O
- O
6 O
weeks O
of O
glucocorticoid O
treatment O
have O
steroid O
- O
resistant O
nephrotic O
syndrome O
( O
SRNS O
) O
. O
In O
10 B-STAT
- O
30 O
% O
of O
steroid O
- O
resistant O
patients O
, O
mutations O
in O
podocyte O
- O
associated O
genes O
can O
be O
detected O
, O
whereas O
an O
undefined O
circulating O
factor O
of O
immune O
origin O
is O
assumed O
in O
the O
remaining O
ones O
. O
Diagnosis O
and O
management O
of O
SRNS O
is O
a O
great O
challenge O
due O
to O
its O
heterogeneous O
etiology O
, O
frequent O
lack O
of O
remission O
by O
further O
immunosuppressive O
treatment O
, O
and O
severe O
complications O
including O
the O
development O
of O
end O
- O
stage O
kidney O
disease O
and O
recurrence O
after O
renal O
transplantation O
. O
A O
team O
of O
experts O
including O
pediatric O
nephrologists O
and O
renal O
geneticists O
from O
the O
International O
Pediatric O
Nephrology O
Association O
( O
IPNA O
) O
, O
a O
renal O
pathologist O
, O
and O
an O
adult O
nephrologist O
have O
now O
developed O
comprehensive O
clinical O
practice O
recommendations O
on O
the O
diagnosis O
and O
management O
of O
SRNS O
in O
children O
. O
The O
team O
performed O
a O
systematic O
literature O
review O
on O
9 O
clinically O
relevant O
PICO O
( O
Patient O
or O
Population O
covered O
, O
Intervention O
, O
Comparator O
, O
Outcome O
) O
questions O
, O
formulated O
recommendations O
and O
formally O
graded O
them O
at O
a O
consensus O
meeting O
, O
with O
input O
from O
patient O
representatives O
and O
a O
dietician O
acting O
as O
external O
advisors O
and O
a O
voting O
panel O
of O
pediatric O
nephrologists O
. O
Research O
recommendations O
are O
also O
given O
. O
Primary O
hyperaldosteronism O
( O
PA O
) O
is O
a O
common O
disease O
with O
a O
prevalence B-EPI
of O
5 B-STAT
- O
10 O
% O
in O
unselected O
patients O
with O
hypertension O
. O
Medullary O
nephrocalcinosis O
is O
a O
radiological O
diagnosis O
and O
refers O
to O
diffuse O
calcification O
in O
the O
renal O
parenchyma O
. O
The O
three O
commonest O
causes O
of O
nephrocalcinosis O
are O
hyperparathyroidism O
, O
distal O
renal O
tubular O
acidosis O
, O
and O
medullary O
sponge O
kidney O
. O
PA O
is O
not O
a O
recognized O
cause O
of O
nephrocalcinosis O
. O
There O
are O
a O
few O
case O
reports O
linking O
PA O
with O
nephrocalcinosis O
published O
till O
date O
. O
In O
this O
case O
series O
, O
we O
report O
three O
cases O
where O
PA O
was O
possibly O
associated O
with O
medullary O
nephrocalcinosis O
. O
In O
all O
three O
cases O
, O
the O
common O
causes O
of O
nephrocalcinosis O
were O
excluded O
by O
careful O
clinical O
history O
, O
biochemical O
evaluation O
, O
and O
radiological O
findings O
. O
We O
conclude O
and O
emphasize O
that O
a O
diagnosis O
of O
PA O
as O
an O
etiology O
of O
medullary O
nephrocalcinosis O
should O
be O
sought O
after O
common O
causes O
have O
been O
excluded O
, O
at O
least O
in O
those O
with O
hypertension O
that O
is O
difficult O
to O
control O
. O
The O
definition O
of O
congenital O
anomalies O
of O
the O
kidney O
and O
urinary O
tract O
( O
CAKUT O
) O
is O
the O
disease O
of O
structural O
malformations O
in O
the O
kidney O
and/or O
urinary O
tract O
containing O
vesicoureteral O
reflux O
( O
VUR O
) O
. O
These O
anomalies O
can O
cause O
pediatric O
chronic O
kidney O
disease O
. O
However O
, O
the O
pathogenesis O
of O
CAKUT O
is O
not O
well O
understood O
, O
because O
identifying O
the O
genetic O
architecture O
of O
CAKUT O
is O
difficult O
due O
to O
the O
phenotypic O
heterogeneity O
and O
multifactorial O
genetic O
penetrance O
. O
We O
describe O
the O
current O
genetic O
basis O
and O
mechanisms O
of O
CAKUT O
including O
VUR O
via O
approaching O
the O
steps O
and O
signaling O
pathways O
of O
kidney O
developmental O
processes O
. O
We O
also O
focus O
on O
the O
newly O
developed O
strategies O
and O
challenges O
to O
fully O
address O
the O
role O
of O
the O
associated O
genes O
in O
the O
pathogenesis O
of O
the O
disease O
. O
White O
- O
tailed O
deer O
( O
WTD O
) O
are O
abundant O
mammals O
widely O
distributed O
across O
the B-LOC
United I-LOC
States I-LOC
. O
As O
a O
result O
, O
WTD O
are O
considered O
to O
be O
excellent O
sentinels O
for O
detecting O
arboviral O
activity O
in O
certain O
geographic O
areas O
. O
Evidence O
of O
West B-LOC
Nile I-LOC
virus O
( O
WNV O
) O
antibody O
in O
WTD O
has O
been O
reported O
previously O
in O
several O
states O
. O
However O
, O
WNV O
infection O
in O
WTD O
has O
not O
been O
reported O
from O
Texas B-LOC
, O
where O
the O
incidence B-EPI
of O
human O
West B-LOC
Nile I-LOC
( O
WN O
) O
cases O
is O
among O
the O
highest O
in O
the B-LOC
United I-LOC
States I-LOC
. O
Therefore O
, O
the O
aim O
of O
this O
study O
was O
to O
determine O
the O
prevalence B-EPI
of O
WNV O
antibody O
in O
WTD O
in O
central O
Texas B-LOC
. O
Sera B-LOC
samples O
( O
n O
= O
644 O
) O
were O
collected O
from O
deer O
during O
the O
fall O
and O
winter O
in O
western O
Travis B-LOC
County I-LOC
, O
Texas B-LOC
from O
2014 O
to O
2018 O
and O
tested O
for O
WNV O
immunoglobulin O
G O
( O
IgG O
) O
antibody O
by O
an O
indirect O
enzyme O
- O
linked O
immunosorbent O
assay O
( O
ELISA O
) O
. O
ELISA O
antibody O
- O
positive O
samples O
were O
further O
tested O
for O
WNV O
and O
St. B-LOC
Louis I-LOC
encephalitis O
virus O
( O
SLEV O
) O
antibodies O
by O
an O
80 O
% O
plaque O
- O
reduction O
neutralization O
tests O
( O
PRNT O
80 O
) O
. O
Overall O
, O
9 O
% O
( O
n O
= O
58 O
) O
and O
0.31 B-STAT
% I-STAT
( O
n O
= O
2 O
) O
of O
the O
deer O
samples O
had O
serological O
evidence O
of O
WNV O
and O
SLEV O
infections O
, O
respectively O
. O
WNV O
seroprevalence O
differed O
significantly O
by O
age O
( O
p O
< O
0.05 O
) O
, O
but O
there O
was O
no O
significant O
difference O
between O
sex O
. O
Interestingly O
, O
3.1 O
% O
( O
n O
= O
20 O
) O
of O
the O
samples O
were O
positive O
for O
Flavivirus O
IgG O
antibody O
by O
ELISA O
, O
but O
negative O
for O
SLEV O
and O
WNV O
antibodies O
, O
suggesting O
that O
other O
Flaviviruses O
may O
be O
circulating O
among O
WTD O
in O
Texas B-LOC
. O
Finally O
, O
these O
results O
supported O
WNV O
infection O
among O
WTD O
and O
highlight O
their O
potential O
role O
as O
sentinels O
for O
the O
detection O
of O
WNV O
in O
Texas B-LOC
and O
warrant O
further O
studies O
to O
determine O
the O
role O
WTD O
play O
in O
the O
maintenance O
and O
transmission O
of O
WNV O
. O
Objectives O
To O
analyse O
the O
characteristics O
and O
predictors O
of O
death O
in O
hospitalized O
patients O
with O
coronavirus O
disease O
2019 O
( O
COVID-19 O
) O
in O
Spain B-LOC
. O
Methods O
A O
retrospective O
observational O
study O
was O
performed O
of O
the O
first O
consecutive O
patients O
hospitalized O
with O
COVID-19 O
confirmed O
by O
real O
- O
time O
PCR O
assay O
in O
127 O
Spanish O
centres O
until O
17 O
March O
2020 O
. O
The O
follow O
- O
up O
censoring O
date O
was O
17 O
April O
2020 O
. O
We O
collected O
demographic O
, O
clinical O
, O
laboratory O
, O
treatment O
and O
complications O
data O
. O
The O
primary O
endpoint O
was O
all O
- O
cause O
mortality O
. O
Univariable O
and O
multivariable O
Cox O
regression O
analyses O
were O
performed O
to O
identify O
factors O
associated O
with O
death O
. O
Results O
Of O
the O
4035 O
patients O
, O
male O
subjects O
accounted O
for O
2433 O
( O
61.0 O
% O
) O
of O
3987 O
, O
the O
median O
age O
was O
70 O
years O
and O
2539 O
( O
73.8 O
% O
) O
of O
3439 O
had O
one O
or O
more O
comorbidity O
. O
The O
most O
common O
symptoms O
were O
a O
history O
of O
fever O
, O
cough O
, O
malaise O
and O
dyspnoea O
. O
During O
hospitalization O
, O
1255 O
( O
31.5 O
% O
) O
of O
3979 O
patients O
developed O
acute O
respiratory O
distress O
syndrome O
, O
736 B-STAT
( O
18.5 O
% O
) O
of O
3988 O
were O
admitted O
to O
intensive O
care O
units O
and O
619 B-STAT
( O
15.5 O
% O
) O
of O
3992 O
underwent O
mechanical O
ventilation O
. O
Virus- O
or O
host O
- O
targeted O
medications O
included O
lopinavir O
/ O
ritonavir O
( O
2820/4005 O
, O
70.4 O
% O
) O
, O
hydroxychloroquine O
( O
2618/3995 O
, O
65.5 O
% O
) O
, O
interferon O
beta O
( O
1153/3950 O
, O
29.2 O
% O
) O
, O
corticosteroids O
( O
1109/3965 O
, O
28.0 O
% O
) O
and O
tocilizumab O
( O
373/3951 B-STAT
, O
9.4 O
% O
) O
. O
Overall O
, O
1131 O
( O
28 O
% O
) O
of O
4035 O
patients O
died O
. O
Mortality O
increased O
with O
age O
( O
85.6 O
% O
occurring O
in O
older O
than O
65 O
years O
) O
. O
Seventeen O
factors O
were O
independently O
associated O
with O
an O
increased O
hazard O
of O
death O
, O
the O
strongest O
among O
them O
including O
advanced O
age O
, O
liver O
cirrhosis O
, O
low O
age O
- O
adjusted O
oxygen O
saturation O
, O
higher O
concentrations O
of O
C O
- O
reactive O
protein O
and O
lower O
estimated O
glomerular O
filtration O
rate O
. O
Conclusions O
Our O
findings O
provide O
comprehensive O
information O
about O
characteristics O
and O
complications O
of O
severe O
COVID-19 O
, O
and O
may O
help O
clinicians O
identify O
patients O
at O
a O
higher O
risk O
of O
death O
. O
Organ O
damage O
in O
sickle O
cell O
disease O
( O
SCD O
) O
is O
a O
crucial O
determinant O
for O
disease O
severity O
and O
prognosis O
. O
In O
a O
previous O
study O
, O
we O
analyzed O
the O
prevalence B-EPI
of O
SCD O
- O
related O
organ O
damage O
and O
complications O
in O
adult O
sickle O
cell O
patients O
. O
We O
now O
describe O
a O
seven O
- O
year O
follow O
- O
up O
of O
this O
cohort O
. O
All O
patients O
from O
the O
primary O
analysis O
in O
2006 O
( O
n O
= O
104 O
) O
, O
were O
included O
for O
follow O
- O
up O
. O
Patients O
were O
screened O
for O
SCD O
- O
related O
organ O
damage O
and O
complications O
( O
microalbuminuria O
, O
renal O
failure O
, O
elevated O
tricuspid O
regurgitation O
flow O
velocity O
( O
TRV O
) O
( O
≥2.5 O
m O
/ O
seconds O
) O
, O
retinopathy O
, O
iron O
overload O
, O
cholelithiasis O
, O
avascular O
osteonecrosis O
, O
leg O
ulcers O
, O
acute O
chest O
syndrome O
( O
ACS O
) O
, O
stroke O
, O
priapism O
and O
admissions O
for O
vaso O
- O
occlusive O
crises O
( O
VOC O
) O
biannually O
. O
Upon O
7 O
years O
of O
follow O
- O
up O
, O
progression O
in O
the O
prevalence B-EPI
of O
avascular O
osteonecrosis O
( O
from O
12.5 O
% O
to O
20.4 O
% O
) O
, O
renal O
failure O
( O
from O
6.7 O
% O
to O
23.4 O
% O
) O
, O
retinopathy O
( O
from O
39.7 O
% O
to O
53.8 O
% O
) O
was O
observed O
in O
the O
whole O
group O
. O
In O
HbSS B-LOC
/ O
HbSβ O
0 O
-thal O
patients O
also O
progression O
in O
microalbuminuria O
( O
from O
34 O
% O
to O
45 O
% O
) O
and O
elevated O
TRV O
( O
from O
40 O
% O
to O
48 O
% O
) O
was O
observed O
while O
hardly O
any O
progression O
in O
the O
prevalence B-EPI
of O
cholelithiasis O
, O
priapism O
, O
stroke O
or O
chronic O
ulcers O
was O
seen O
. O
The O
proportion O
of O
patients O
with O
at O
least O
one O
episode O
of O
ACS O
increased O
in O
the O
group O
of O
HbSS B-LOC
/ O
HbSβ O
0 O
-thal O
patients O
from O
32 O
% O
to O
49.1 O
% I-STAT
. O
In O
conclusion O
, O
62 O
% O
of O
the O
sickle O
cell O
patients O
in O
this O
prospective O
cohort O
study O
developed O
a O
new O
SCD O
- O
related O
complication O
in O
a O
comprehensive O
care O
setting O
within O
7 O
years O
of O
follow O
- O
up O
. O
Although O
the O
hospital O
admission O
rate O
for O
VOC O
remained O
stable O
, O
multiple O
forms O
of O
organ O
damage O
increased O
substantially O
. O
These O
observations O
underline O
the O
need O
for O
continued O
screening O
for O
organ O
damage O
in O
all O
adult O
patients O
with O
SCD O
. O
BACKGROUND O
: O
Intellectual O
disability O
( O
ID O
) O
affects O
1 B-STAT
- O
3 O
% O
of O
the O
Western O
population O
and O
is O
heterogeneous O
in O
origin O
. O
Mutations O
in O
X O
- O
linked O
genes O
represent O
5 B-STAT
- O
10 O
% O
of O
ID O
in O
males O
. O
Fragile O
X O
syndrome O
, O
due O
to O
the O
silencing O
of O
the O
FMR1 O
gene O
, O
is O
the O
most O
common O
form O
of O
ID O
, O
with O
a O
prevalence B-EPI
of O
around B-STAT
1:5000 I-STAT
males I-STAT
. I-STAT
Females O
are O
usually O
non- O
or O
mildly O
affected O
carriers O
, O
and O
in O
a O
few O
rare O
cases O
, O
the O
only O
gender O
affected O
. O
Array O
comparative O
genome O
hybridization O
( O
aCGH O
) O
and O
next O
- O
generation O
sequencing O
( O
NGS O
) O
have O
dramatically O
changed O
the O
nature O
of O
human O
genome O
analysis O
leading O
to O
the O
identification O
of O
new O
X O
- O
linked O
intellectual O
disability O
syndromes O
and O
disease O
- O
causing O
genes O
. O
SOURCES O
OF O
DATA O
: O
Original O
papers O
, O
reviews O
, O
guidelines O
and O
experiences O
of O
the O
diagnostic O
laboratories O
. O
AREAS O
OF O
AGREEMENT O
: O
Family O
history O
and O
clinical O
examination O
still O
are O
essential O
to O
choose O
the O
appropriate O
diagnostic O
tests O
, O
including O
, O
a O
disease O
- O
specific O
genetic O
test O
, O
aCGH O
or O
FMR1 O
molecular O
analysis O
. O
If O
negative O
, O
NGS O
approaches O
like O
well O
- O
defined O
gene O
panels O
, O
whole O
exome O
, O
or O
even O
whole O
genome O
sequencing O
, O
are O
increasingly O
being O
used O
, O
improving O
diagnostics O
and O
leading O
to O
the O
identification O
of O
novel O
disease O
mechanisms O
. O
AREAS O
OF O
CONTROVERSY O
: O
The O
main O
challenge O
in O
the O
era O
of O
NGS O
is O
filtering O
and O
interpretation O
of O
the O
data O
generated O
by O
the O
analysis O
of O
a O
single O
individual O
. O
In O
X O
- O
linked O
cases O
, O
assessing O
pathogenicity O
is O
particularly O
challenging O
, O
even O
more O
when O
the O
variant O
is O
found O
to O
be O
inherited O
from O
a O
healthy O
carrier O
mother O
or O
when O
a O
heterozygous O
X O
- O
linked O
mutation O
is O
found O
in O
an O
impaired O
female O
. O
GROWING O
POINTS O
: O
At O
present O
, O
variant O
interpretation O
remains O
a O
challenging O
task O
, O
especially O
in O
X O
- O
linked O
disorders O
. O
We O
review O
the O
main O
difficulties O
and O
propose O
a O
comprehensive O
overview O
that O
might O
aid O
in O
variant O
interpretation O
. O
Establishing O
a O
genetic O
diagnosis O
facilitates O
counseling O
and O
allows O
better O
delineation O
of O
clinical O
phenotypes O
. O
AREAS O
TIMELY O
FOR O
DEVELOPING O
RESEARCH O
: O
To O
improve O
variant O
interpretation O
, O
there O
is O
need O
to O
refine O
in O
silico O
predictions O
with O
specific O
criteria O
for O
each O
gene O
, O
and O
to O
develop O
cost O
- O
effective O
functional O
tools O
, O
which O
can O
be O
easily O
transferred O
to O
diagnostics O
. O
Our O
understanding O
about O
the O
epidemiological O
aspects O
, O
pathogenesis O
, O
molecular O
diagnosis O
, O
and O
targeted O
therapies O
of O
neuroendocrine O
neoplasms O
( O
NENs O
) O
have O
drastically O
advanced O
in O
the O
past O
decade O
. O
Gastroenteropancreatic O
( O
GEP O
) O
NENs O
originate O
from O
the O
enteroendocrine O
cells O
of O
the O
embryonic O
gut O
which O
share O
common O
endocrine O
and O
neural O
differentiation O
factors O
. O
Most O
NENs O
are O
well O
- O
differentiated O
, O
and O
slow O
growing O
. O
Specific O
neuroendocrine O
biomarkers O
that O
are O
used O
in O
the O
diagnosis O
of O
functional O
NENs O
include O
insulin O
, O
glucagon O
, O
vasoactive O
intestinal O
polypeptide O
, O
gastrin O
, O
somatostatin O
, O
adrenocorticotropin O
, O
growth O
hormone O
releasing O
hormone O
, O
parathyroid O
hormone O
- O
related O
peptide O
, O
serotonin O
, O
histamine O
, O
and O
5 O
- O
hydroxy O
indole O
acetic O
acid O
( O
5 O
- O
HIAA O
) O
. O
Biomarkers O
such O
as O
pancreatic O
polypeptide O
, O
human O
chorionic O
gonadotrophin O
subunits O
, O
neurotensin O
, O
ghrelin O
, O
and O
calcitonin O
are O
used O
in O
the O
diagnosis O
of O
non O
- O
functional O
NENs O
. O
5 O
- O
HIAA O
levels O
correlate O
with O
tumour O
burden O
, O
prognosis O
and O
development O
of O
carcinoid O
heart O
disease O
and O
mesenteric O
fibrosis O
, O
however O
several O
diseases O
, O
medications O
and O
edible O
products O
can O
falsely O
elevate O
the O
5 O
- O
HIAA O
levels O
. O
Organ O
- O
specific O
transcription O
factors O
are O
useful O
in O
the O
differential O
diagnosis O
of O
metastasis O
from O
an O
unknown O
primary O
of O
well O
- O
differentiated O
NENs O
. O
Emerging O
novel O
biomarkers O
include O
circulating O
tumour O
cells O
, O
circulating O
tumour O
DNA O
, O
circulating O
micro O
- O
RNAs O
, O
and O
neuroendocrine O
neoplasms O
test O
( O
NETest O
) O
( O
simultaneous O
measurement O
of O
51 O
neuroendocrine O
- O
specific O
marker O
genes O
in O
the O
peripheral O
blood O
) O
. O
NETest O
has O
high O
sensitivity O
( O
85%-98 O
% O
) O
and O
specificity O
( O
93%-97 O
% O
) O
for O
the O
detection O
of O
gastrointestinal O
NENs O
, O
and O
is O
useful O
for O
monitoring O
treatment O
response O
, O
recurrence O
, O
and O
prognosis O
. O
In O
terms O
of O
management O
, O
surgery O
, O
radiofrequency O
ablation O
, O
symptom O
control O
with O
medications O
, O
chemotherapy O
and O
molecular O
targeted O
therapies O
are O
all O
considered O
as O
options O
. O
Surgery O
is O
the O
mainstay O
of O
treatment O
, O
but O
depends O
on O
factors O
including O
age O
of O
the O
individual O
, O
location O
, O
stage O
, O
grade O
, O
functional O
status O
, O
and O
the O
heredity O
of O
the O
tumour O
( O
sporadic O
vs O
inherited O
) O
. O
Medical O
management O
is O
helpful O
to O
alleviate O
the O
symptoms O
, O
manage O
inoperable O
lesions O
, O
suppress O
postoperative O
tumour O
growth O
, O
and O
manage O
recurrences O
. O
Several O
molecular O
- O
targeted O
therapies O
are O
considered O
second O
line O
to O
somatostatin O
analogues O
. O
This O
review O
is O
a O
clinical O
update O
on O
the O
pathophysiological O
aspects O
, O
diagnostic O
algorithm O
, O
and O
management O
of O
GEP O
NENs O
. O
Background O
Kawasaki O
disease O
( O
KD O
) O
incidence B-EPI
is O
increasing O
in O
Ontario B-LOC
. O
Cardiovascular O
sequelae O
following O
KD O
are O
well O
- O
described O
. O
However O
, O
there O
are O
limited O
data O
on O
non O
- O
cardiovascular O
outcomes O
. O
Objectives O
To O
determine O
the O
risk O
of O
hearing O
loss O
, O
anxiety O
, O
developmental O
disorders O
, O
intellectual O
disabilities O
and O
attention O
- O
deficit O
/ O
hyperactivity O
disorder O
( O
ADHD O
) O
among O
KD O
survivors O
vs. O
non O
- O
exposed O
children O
. O
Methods O
We O
included O
all O
Ontario O
children O
( O
≤18 O
yr O
) O
surviving O
hospitalization O
with O
a O
KD O
diagnosis O
between O
1995 O
and O
2018 O
, O
using O
population O
- O
based O
health O
administrative O
databases O
. O
We O
excluded O
children O
with O
prior O
KD O
diagnoses O
and O
non O
- O
residents O
. O
KD O
cases O
were O
matched O
with O
100 O
non O
- O
exposed O
children O
by O
age O
, O
sex O
and O
year O
. O
Follow O
- O
up O
continued O
until O
death O
or O
March O
2019 O
. O
We O
calculated O
the O
prevalence B-EPI
, O
incidence B-EPI
and O
adjusted O
hazard O
ratios O
( O
aHR O
[ O
95%CI O
] O
) O
of O
outcomes O
between O
0 O
- O
1 O
yr O
, O
1 B-STAT
- I-STAT
5 I-STAT
yr O
, O
5 O
- O
10 O
yr O
and O
> O
10 O
yr O
follow O
- O
up O
. O
Results O
Among O
4597 O
KD O
survivors O
, O
364 B-STAT
( O
7.9 O
% O
) O
were O
diagnosed O
with O
hearing O
loss O
, O
1213 O
( O
26.4 O
% O
) O
anxiety O
disorders O
, O
398 B-STAT
( O
8.7 O
% O
) O
developmental O
disorders O
, O
51 B-STAT
( O
1.1 O
% O
) O
intellectual O
disability O
and O
21 B-STAT
( I-STAT
0.5 I-STAT
% I-STAT
) O
ADHD O
, O
during O
median O
11 O
year O
follow O
- O
up O
. O
Compared O
to O
459,700 O
non O
- O
exposed O
children O
, O
KD O
survivors O
were O
not O
at O
increased O
risk O
of O
hearing O
loss O
after O
adjustment O
for O
potential O
confounders O
. O
KD O
survivors O
were O
at O
increased O
risk O
of O
anxiety O
disorders O
between O
0 O
- O
1 O
yr O
( O
aHR O
1.75 O
[ O
1.46 O
- O
2.10 O
] O
) O
, O
1 B-STAT
- I-STAT
5 I-STAT
yr O
( O
aHR O
1.13 O
[ O
1.01 O
- O
1.28 O
] O
) O
, O
5 O
- O
10 O
yr O
( O
aHR O
1.14 O
[ O
1.03 O
- O
1.28 O
] O
) O
and O
> O
10 O
yr O
( O
aHR O
1.11 O
[ O
1.02 O
- O
1.22 O
] O
) O
; O
developmental O
disorders O
between O
0 B-STAT
- I-STAT
1 I-STAT
yr I-STAT
( O
aHR O
1.49 O
[ O
1.28 O
- O
1.74 O
] O
) O
and O
1 O
- O
5 O
yr O
( O
aHR O
1.19 O
[ O
1.02 O
- O
1.40 O
] O
) O
; O
intellectual O
disabilities O
> O
10 O
yr O
( O
aHR O
2.36 O
[ O
1.36 O
- O
4.10 O
] O
) O
; O
and O
ADHD O
> O
10 O
yr O
( O
aHR O
2.01 O
[ O
1.14 O
- O
3.57 O
] O
) O
. O
Conclusions O
KD O
survivors O
are O
at O
increased O
risk O
of O
being O
diagnosed O
with O
anxiety O
disorders O
sooner O
, O
being O
diagnosed O
with O
developmental O
disorders O
between O
0 O
and O
5 O
yr O
and O
being O
diagnosed O
with O
intellectual O
disabilities O
or O
ADHD O
> O
10 O
yr O
after O
KD O
diagnosis O
. O
This O
may O
justify O
enhanced O
developmental O
and O
audiological O
surveillance O
of O
KD O
survivors O
. O
Down O
syndrome O
( O
DS O
) O
is O
the O
most O
common O
chromosome O
abnormality O
with O
a O
unique O
cancer O
predisposition O
syndrome O
pattern O
: O
a O
higher O
risk O
to O
develop O
acute O
leukemia O
and O
a O
lower O
incidence B-EPI
of O
solid O
tumors O
. O
In O
particular O
, O
brain O
tumors O
are O
rarely O
reported O
in O
the O
DS O
population O
, O
and O
biological O
behavior O
and O
natural O
history O
are O
not O
well O
described O
and O
identified O
. O
We O
report O
a O
case O
of O
a O
10 O
- O
year O
- O
old O
child O
with O
DS O
who O
presented O
with O
a O
medulloblastoma O
( O
MB O
) O
. O
Histological O
examination O
revealed O
a O
classic O
MB O
with O
focal O
anaplasia O
and O
the O
molecular O
profile O
showed O
the O
presence O
of O
a O
CTNNB1 O
variant O
associated O
with O
the O
wingless O
( O
WNT O
) O
molecular O
subgroup O
with O
a O
good O
prognosis O
in O
contrast O
to O
our O
case O
report O
that O
has O
shown O
an O
early O
metastatic O
relapse O
. O
The O
nearly O
seven O
- O
fold O
decreased O
risk O
of O
MB O
in O
children O
with O
DS O
suggests O
the O
presence O
of O
protective O
biological O
mechanisms O
. O
The O
cerebellum O
hypoplasia O
and O
the O
reduced O
volume O
of O
cerebellar O
granule O
neuron O
progenitor O
cells O
seem O
to O
be O
a O
possible O
favorable O
condition O
to O
prevent O
MB O
development O
via O
inhibition O
of O
neuroectodermal O
differentiation O
. O
Moreover O
, O
the O
NOTCH O
/ O
WNT O
dysregulation O
in O
DS O
, O
which O
is O
probably O
associated O
with O
an O
increased O
risk O
of O
leukemia O
, O
suggests O
a O
pivotal O
role O
of O
this O
pathway O
alteration O
in O
the O
pathogenesis O
of O
MB O
; O
therefore O
, O
this O
condition O
should O
be O
further O
investigated O
in O
future O
studies O
by O
molecular O
characterizations O
. O
The O
end O
- O
of O
- O
outbreak O
declaration O
is O
an O
important O
step O
in O
controlling O
infectious O
disease O
outbreaks O
. O
Objective O
estimation O
of O
the O
confidence O
level O
that O
an O
outbreak O
is O
over O
is O
important O
to O
reduce O
the O
risk O
of O
postdeclaration O
flare O
- O
ups O
. O
We O
developed O
a O
simulation O
- O
based O
model O
with O
which O
to O
quantify O
that O
confidence O
and O
tested O
it O
on O
simulated O
Ebola O
virus O
disease O
data O
. O
We O
found O
that O
these O
confidence O
estimates O
were O
most O
sensitive O
to O
the O
instantaneous O
reproduction O
number O
, O
the O
reporting O
rate O
, O
and O
the O
time O
between O
the O
symptom O
onset O
and O
death O
or O
recovery O
of O
the O
last O
detected O
case O
. O
For O
Ebola O
virus O
disease O
, O
our O
results O
suggested O
that O
the O
current O
World O
Health O
Organization O
criterion O
of O
42 O
days O
since O
the O
recovery O
or O
death O
of O
the O
last O
detected O
case O
is O
too O
short O
and O
too O
sensitive O
to O
underreporting O
. O
Therefore O
, O
we O
suggest O
a O
shift O
to O
a O
preliminary O
end O
- O
of O
- O
outbreak O
declaration O
after O
63 O
days O
from O
the O
symptom O
onset O
day O
of O
the O
last O
detected O
case O
. O
This O
preliminary O
declaration O
should O
still O
be O
followed O
by O
90 O
days O
of O
enhanced O
surveillance O
to O
capture O
potential O
flare O
- O
ups O
of O
cases O
, O
after O
which O
the O
official O
end O
of O
the O
outbreak O
can O
be O
declared O
. O
This O
sequence O
corresponds B-STAT
to I-STAT
more I-STAT
than O
95 O
% O
confidence O
that O
an O
outbreak O
is O
over O
in O
most O
of O
the O
scenarios O
examined O
. O
Our O
framework O
is O
generic O
and O
therefore O
could O
be O
adapted O
to O
estimate O
end O
- O
of O
- O
outbreak O
confidence O
for O
other O
infectious O
diseases O
. O
Background O
Biatrial O
tachycardia O
( O
BiAT O
) O
is O
a O
rare O
form O
of O
macroreentry O
not O
previously O
characterized O
in O
adults O
with O
congenital O
heart O
disease O
( O
ACHD O
) O
OBJECTIVE O
: O
To O
determine O
the O
prevalence B-EPI
, O
mechanisms O
and O
outcomes O
of O
catheter O
ablation O
for O
BiAT O
in O
ACHD O
. O
Methods O
All O
ACHD O
undergoing O
catheter O
ablation O
for O
macroreentrant O
atrial O
tachycardia O
over O
a O
10 O
- O
year O
period O
were O
evaluated O
for O
evidence O
of O
BiAT O
. O
Patient O
s O
were O
categorized O
as O
prior O
Senning B-LOC
, O
Fontan O
or O
other O
biventricular O
operation O
. O
A O
novel O
biatrial O
global O
activation O
histogram O
( O
GAH O
) O
analysis O
was O
used O
to O
demonstrate O
the O
presence O
of O
interatrial O
connections O
( O
IAC O
) O
. O
Results O
Among O
263 O
ACHD O
, O
BiAT O
was O
identified O
at O
11 O
procedures O
in O
10 O
patients O
( O
4.2 O
% O
; O
median O
age O
35 O
y O
; O
30 O
% O
male O
) O
. O
The O
congenital O
category O
was O
Fontan O
in O
6 O
, O
Senning B-LOC
in O
3 O
and O
biventricular O
in O
2 O
. O
Diagnosis O
of O
BiAT O
was O
associated O
with O
ablation O
era O
and O
mapping O
technology O
( O
p<0.001 O
) O
and O
could O
be O
confirmed O
with O
a O
novel O
GAH O
mapping O
approach O
for O
normally O
- O
septated O
atrial O
connections O
. O
Catheter O
ablation O
targeted O
an O
IAC O
in O
5 O
cases O
( O
Bjork O
Fontan O
/ O
biventricular O
operations O
) O
, O
a O
posterior O
isthmus O
in O
3 O
( O
Senning B-LOC
operation O
) O
and O
the O
cavo O
- O
tricuspid O
isthmus O
( O
CTI O
) O
or O
equivalent O
in O
3 O
( O
LT O
Fontan O
) O
. O
Recurrence O
was O
isolated O
to O
ablation O
to O
sites O
at O
the O
expected O
location O
of O
Bachmann O
's O
bundle O
( O
BB O
) O
, O
and O
durable O
success O
could O
be O
achieved O
after O
repeat O
ablation O
. O
Conclusion O
BiAT O
occurs B-EPI
in O
approximately O
4 O
% O
of O
ACHD O
but O
is O
likely O
significantly O
underrecognized O
. O
BiAT O
could O
be O
targeted O
at O
an O
IAC O
after O
biventricular O
heart O
/ O
Bjork O
modified O
Fontan O
operations O
and O
at O
a O
conventional O
critical O
isthmus O
after O
Senning B-LOC
and O
LT O
Fontan O
operations O
. O
Objectives O
To O
determine O
the O
incidence B-EPI
of O
newborn O
screening O
( O
NBS O
) O
disorders O
and O
to O
study O
the O
key O
performance O
indicators O
of O
the O
program O
. O
Methods O
This O
retrospective O
single O
- O
center O
study O
enrolled O
all O
infants O
who O
underwent O
NBS O
from O
January O
2012 O
to O
December O
2017 O
at O
Prince O
Sultan O
Military O
Medical O
City O
, O
Riyadh B-LOC
, O
Saudi B-LOC
Arabia I-LOC
. O
We O
screened O
17 O
NBS O
disorders O
. O
Blood O
samples O
were O
collected O
24 O
hours O
after O
birth O
. O
If O
the O
initial O
result O
was O
positive O
, O
a O
second O
sample O
was O
collected O
. O
True O
positive O
cases O
were O
immediately O
referred O
for O
medical O
management O
. O
Data O
were O
extracted O
from O
laboratory O
computerized O
and O
non O
- O
computerized O
records O
using O
case O
report O
forms O
. O
Results O
During O
the O
study O
period O
, O
56632 O
infants O
underwent O
NBS O
with O
a O
coverage O
rate O
of O
100 B-STAT
% I-STAT
. O
Thirty O
- O
eight O
cases O
were O
confirmed O
. O
The O
incidence B-EPI
of O
congenital O
hypothyroidism O
was O
1:3775 O
. O
The O
positive O
predictive O
value O
for O
the O
detection O
of O
congenital O
hypothyroidism O
was O
11.8 B-STAT
% I-STAT
. O
Propionic O
aciduria O
was O
the O
most O
common O
metabolic O
disorder O
, O
with O
an O
incidence B-EPI
of O
1:14158 O
. O
Very O
long O
- O
chain O
acyl O
CoA O
dehydrogenase O
deficiency O
and O
glutaric O
aciduria O
type O
1 O
had O
an O
incidence B-EPI
of O
1:18877 B-STAT
each O
. O
Phenylketonuria O
, O
biotinidase O
deficiency O
, O
maple O
syrup O
urine O
disease O
, O
and O
citrullinemia O
had O
an O
incidence B-EPI
of O
1:28316 B-STAT
each O
. O
However O
, O
galactosemia O
and O
3 O
- O
methyl O
crotonyl O
carboxylase O
deficiency O
had O
the O
lowest O
incidence B-EPI
of O
1:56632 O
. O
Conclusion O
The O
NBS O
coverage O
rate O
at O
our O
facility O
was O
100 B-STAT
% I-STAT
. O
Congenital O
hypothyroidism O
was O
the O
most O
frequently O
detected O
disorder O
with O
an O
incidence B-EPI
that O
matches O
worldwide B-LOC
figures O
. O
The O
incidence B-EPI
of O
other O
inherited O
disorders O
was O
consistent O
with O
regional O
figures O
. O
There O
is O
an O
urgent O
public O
health O
need O
to O
better O
understand O
Severe O
Acute O
Respiratory O
Syndrome O
( O
SARS)-CoV-2 O
/ O
COVID-19 O
, O
particularly O
how O
sequences O
of O
the O
viruses O
could O
lead O
to O
diverse O
incidence B-EPI
and O
mortality O
of O
COVID-19 O
in O
different O
countries O
. O
However O
, O
because O
of O
its O
unknown O
ancestors O
and O
hosts O
, O
elucidating O
the O
genetic O
variations O
of O
the O
novel O
coronavirus O
, O
SARS O
- O
CoV-2 O
, O
has O
been O
difficult O
. O
Without O
needing O
to O
know O
ancestors O
, O
we O
identified O
an O
uneven O
distribution O
of O
local O
genome O
similarities O
among O
the O
viruses O
categorized O
by O
geographic O
regions O
, O
and O
it O
was O
strongly O
correlated O
with O
incidence B-EPI
and O
mortality O
. O
To O
ensure O
unbiased O
and O
origin O
- O
independent O
analyses O
, O
we O
used O
a O
pairwise O
comparison O
of O
local O
genome O
sequences O
of O
virus O
genomes O
by O
Basic O
Local O
Alignment O
Search O
Tool O
( O
BLAST O
) O
. O
We O
found O
a O
strong O
statistical O
correlation O
between O
dominance O
of O
the O
SARS O
- O
CoV-2 O
in O
distributions O
of O
uneven O
similarities O
and O
the O
incidence B-EPI
and O
mortality O
of O
illness O
. O
Genomic O
annotation O
of O
the O
BLAST O
hits O
also O
showed O
that O
viruses O
from O
geographic O
regions O
with O
severe O
infections O
tended O
to O
have O
more O
dynamic O
genomic O
regions O
in O
the O
SARS O
- O
CoV-2 O
receptor O
- O
binding O
domain O
( O
RBD O
) O
and O
receptor O
- O
binding O
motif O
( O
RBM O
) O
of O
the O
spike O
protein O
( O
S O
protein O
) O
. O
Dynamic O
domains O
in O
the O
S O
protein O
were O
also O
confirmed O
by O
a O
canyon O
region O
of O
mismatches O
coincident O
with O
RBM O
and O
RBD O
, O
without O
hits O
of O
alignments O
of O
100 O
% O
matching O
. O
Thus O
, O
our O
origin O
- O
independent O
analysis O
suggests O
that O
the O
dynamic O
and O
unstable O
SARS O
- O
CoV-2 O
- O
RBD O
could O
be O
the O
main O
reason O
for O
diverse O
incidence B-EPI
and O
mortality O
of O
COVID-19 O
infection O
. O
Our O
knowledge O
about O
inherited O
susceptibility O
to O
adrenocortical O
carcinoma O
( O
ACC O
) O
almost O
exclusively O
stems O
from O
experiences O
with O
familial O
cancer O
susceptibility O
syndromes O
, O
which O
are O
caused O
by O
single O
gene O
mutations O
( O
e.g. O
Li O
- O
Fraumeni O
syndrome O
( O
LFS O
) O
) O
. O
Population O
- O
based O
studies O
are O
largely O
unavailable O
. O
ACC O
diagnosed O
during O
childhood O
is O
known O
to O
be O
commonly O
part O
of O
hereditary O
cancer O
syndromes O
. O
Childhood O
ACC O
is O
part O
of O
the O
classical O
tumor O
spectrum O
of O
LFS O
and O
Beckwith O
- O
Wiedemann O
syndrome O
( O
BWS O
) O
. O
In O
adults O
ACC O
has O
been O
reported O
in O
patients O
with O
multiple O
endocrine O
neoplasia O
( O
MEN1 O
) O
, O
familial O
adenomatous O
polyposis O
coli O
( O
FAP O
) O
and O
neurofibromatosis O
type O
1 O
( O
NF1 O
) O
. O
However O
, O
the O
evidence O
associating O
ACC O
with O
these O
syndromes O
is O
less O
well O
substantiated O
. O
Here O
, O
we O
will O
review O
the O
evidence O
for O
genetic O
predisposition O
in O
general O
and O
the O
association O
with O
known O
familial O
cancer O
susceptibility O
syndromes O
in O
particular O
. O
We O
will O
also O
review O
current O
recommendations O
regarding O
screening O
and O
surveillance O
of O
these O
patients O
as O
they O
apply O
to O
a O
specialized O
ACC O
or O
endocrine O
cancer O
clinic O
. O
Transient O
global O
amnesia O
( O
TGA O
) O
is O
an O
uncommon O
disease O
characterized O
by O
sudden O
onset O
anterograde O
amnesia O
that O
typically O
improves O
within O
24 O
hours O
. O
A O
35 O
- O
year O
- O
old O
woman O
presented O
with O
complete O
disruption O
of O
memory O
that O
had O
started O
on O
the O
previous O
day O
. O
She O
had O
fever O
and O
heart O
murmur O
and O
was O
diagnosed O
as O
having O
infective O
endocarditis O
with O
Staphylococcus O
lugdunensis O
, O
a O
coagulase O
- O
negative O
staphylococcus O
. O
Septic O
embolizations O
were O
found O
in O
the O
spleen O
and O
kidney O
on O
CT O
scan O
. O
The O
patient O
underwent O
aortic O
valve O
replacement O
. O
MRI O
susceptibility O
- O
weighted O
imaging O
showed O
a O
dotted O
low O
intensity O
area O
in O
the O
right O
hippocampus O
. O
Recently O
, O
etiology O
of O
TGA O
is O
reported O
to O
be O
related O
to O
hippocampal O
disorder O
. O
We O
report O
a O
rare O
case O
of O
TGA O
with O
hippocampal O
infarction O
due O
to O
septic O
embolism O
from O
infective O
endocarditis O
. O
The O
10th O
International O
Meeting O
on O
Neuroacanthocytosis O
Syndromes O
was O
held O
online O
on O
March O
10th12th O
, O
2021 O
. O
The O
COVID19 O
pandemic O
situation O
made O
our O
planned O
meeting O
in O
Barcelona B-LOC
on O
March O
2020 O
to O
be O
suspended O
by O
one O
year O
, O
and O
finally O
took O
place O
online O
. O
The O
meeting O
followed O
the O
previous O
nine O
international O
symposia O
, O
the O
last O
of O
which O
was O
held O
in O
Dresden B-LOC
, O
Germany B-LOC
in O
March O
, O
2018 O
. O
The O
setting O
of O
the O
meeting O
encouraged O
interactions O
, O
exchange O
of O
ideas O
and O
networking O
opportunities O
among O
the O
high O
number O
of O
participants O
from O
around O
the O
globe O
, O
including O
scientists O
, O
neurologists O
and O
specially O
patients O
and O
caregivers O
. O
A O
total O
of O
27 O
oral O
communications O
were O
distributed O
in O
8 O
sessions O
with O
topics O
ranging O
from O
molecular O
and O
cellular O
functions O
of O
VPS13 O
genes O
and O
proteins O
, O
their O
involvement O
in O
Neuroacanthocytosis O
Syndromes O
and O
finally O
clinical O
aspects O
and O
patients O
care O
. O
In O
addition O
, O
5 O
posters O
were O
presented O
. O
Altogether O
, O
scientists O
and O
neurologists O
discussed O
recent O
advances O
and O
set O
the O
bases O
for O
next O
steps O
, O
action O
points O
, O
and O
future O
studies O
in O
close O
collaboration O
with O
the O
patients O
associations O
, O
which O
are O
always O
actively O
involved O
in O
the O
whole O
process O
. O
Charcot O
- O
Marie O
- O
Tooth O
( O
CMT O
) O
is O
the O
most O
prevalent B-EPI
category O
of O
inherited O
neuropathy O
. O
The O
most O
common O
inheritance O
pattern O
is O
autosomal O
dominant O
, O
though O
there O
also O
are O
X O
- O
linked O
and O
autosomal O
recessive O
subtypes O
. O
In O
addition O
to O
a O
variety O
of O
inheritance O
patterns O
, O
there O
are O
a O
myriad O
of O
genes O
associated O
with O
CMT O
, O
reflecting O
the O
heterogeneity O
of O
this O
disorder O
. O
Next O
generation O
sequencing O
( O
NGS O
) O
has O
expanded O
and O
simplified O
the O
diagnostic O
yield O
of O
genes O
/ O
molecules O
underlying O
and/or O
associated O
with O
CMT O
, O
which O
is O
of O
paramount O
importance O
in O
providing O
a O
substrate O
for O
current O
and O
future O
targeted O
disease O
- O
modifying O
treatment O
options O
. O
Considerable O
research O
attention O
for O
disease O
- O
modifying O
therapy O
has O
been O
geared O
towards O
the O
most O
commonly O
encountered O
genetic O
mutations O
( O
PMP22 O
, O
GJB1 O
, O
MPZ O
, O
and O
MFN2 O
) O
. O
In O
this O
review O
, O
we O
highlight O
the O
clinical O
background O
, O
molecular O
understanding O
, O
and O
therapeutic O
investigations O
of O
these O
CMT O
subtypes O
, O
while O
also O
discussing O
therapeutic O
research O
pertinent O
to O
the O
remaining O
less O
common O
CMT O
subtypes O
. O
Purpose O
TP53germline O
( O
g O
) O
mutations O
, O
associated O
with O
the O
Li O
- O
Fraumeni O
syndrome O
( O
LFS O
) O
, O
have O
rarely O
been O
reported O
in O
the O
context O
of O
hereditary O
breast O
and O
ovarian O
cancer O
( O
HBOC O
) O
. O
The O
prevalence B-EPI
and O
cancer O
risks O
in O
this O
target O
group O
are O
unknown O
and O
counseling O
remains O
challenging O
. O
Notably O
an O
extensive O
high O
- O
risk O
surveillance O
program O
is O
implemented O
, O
which O
evokes O
substantial O
psychological O
discomfort O
. O
Emphasizing O
the O
lack O
of O
consensus O
about O
clinical O
implications O
, O
we O
aim O
to O
further O
characterize O
TP53 O
g O
mutations O
in O
HBOC O
families O
. O
Methods O
Next O
- O
generation O
sequencing O
was O
conducted O
on O
1876 O
breast O
cancer O
( O
BC O
) O
patients O
who O
fulfilled O
the O
inclusion O
criteria O
for O
HBOC O
. O
Results O
( O
Likely O
) O
pathogenic O
variants O
in O
TP53 O
gene O
were O
present O
in O
0.6 B-STAT
% I-STAT
of O
the O
BC O
cohort O
with O
higher O
occurrence B-EPI
in O
early O
onset O
BC O
< O
36 O
years O
. O
( O
1.1 O
% O
) O
and O
bilateral O
vs. O
unilateral O
BC O
( O
1.1 O
% O
vs. O
0.3 O
% I-STAT
) O
. O
Two O
out O
of O
eleven O
patients O
with O
a O
( O
likely O
) O
pathogenic O
TP53 O
g O
variant O
( O
c.542 O
G O
> O
A O
; O
c.375 O
G O
> O
A O
) O
did O
not O
comply O
with O
classic O
LFS O
/ O
Chompret O
criteria O
. O
Albeit O
located O
in O
the O
DNA O
- O
binding O
domain O
of O
the O
p53 O
- O
protein O
and O
therefore O
revealing O
no O
difference O
to O
LFS O
- O
related O
variants O
, O
they O
only O
displayed O
a O
medium O
transactivity O
reduction O
constituting O
a O
retainment O
of O
wildtype O
- O
like O
anti O
- O
proliferative O
functionality O
. O
Conclusion O
Among O
our O
cohort O
of O
HBOC O
families O
, O
we O
were O
able O
to O
describe O
a O
clinical O
subgroup O
, O
which O
is O
distinct O
from O
the O
classic O
LFS O
- O
families O
. O
Strikingly O
, O
two O
families O
did O
not O
adhere O
to O
the O
LFS O
criteria O
, O
and O
functional O
analysis O
revealed O
a O
reduced O
impact O
on O
TP53 O
activity O
, O
which O
may O
suit O
to O
the O
attenuated O
phenotype O
. O
This O
is O
an O
approach O
that O
could O
be O
useful O
in O
developing O
individualized O
screening O
efforts O
for O
TP53 O
g O
mutation O
carrier O
in O
HBOC O
families O
. O
Due O
to O
the O
low O
incidence B-EPI
, O
national O
/ O
international O
cooperation O
is O
necessary O
to O
further O
explore O
clinical O
implications O
. O
This O
might O
allow O
providing O
directions O
for O
clinical O
recommendations O
in O
the O
future O
. O
Neonatal O
herpes O
, O
seen O
roughly O
in O
1 B-STAT
of I-STAT
3000 I-STAT
live I-STAT
births I-STAT
in O
the B-LOC
United I-LOC
States I-LOC
, O
is O
the O
most O
serious O
manifestation O
of O
herpes O
simplex O
virus O
( O
HSV O
) O
infection O
in O
the O
perinatal O
period O
. O
Although O
acyclovir O
therapy O
decreases O
infant O
mortality O
associated O
with O
perinatal O
HSV O
transmission O
, O
development O
of O
permanent O
neurological O
disabilities O
is O
not O
uncommon O
. O
Mother O
- O
to O
- O
neonate O
HSV O
transmission O
is O
most O
efficient O
when O
maternal O
genital O
tract O
HSV O
infection O
is O
acquired O
proximate O
to O
the O
time O
of O
delivery O
, O
signifying O
that O
neonatal O
herpes O
prevention O
strategies O
need O
to O
focus O
on O
decreasing O
the O
incidence B-EPI
of O
maternal O
infection O
during O
pregnancy O
and O
more O
precisely O
identifying O
infants O
most O
likely O
to O
benefit O
from O
prophylactic O
antiviral O
therapy O
. O
Purpose O
Inflammatory O
bowel O
diseases O
( O
IBD O
) O
, O
including O
Crohn O
's O
disease O
( O
CD O
) O
and O
ulcerative O
colitis O
( O
UC O
) O
, O
are O
chronic O
diseases O
. O
The O
aim O
was O
to O
validate O
diagnoses O
of O
IBD O
among O
patients O
aged O
50 O
+ O
years O
in O
the O
Danish O
National O
Patient O
Registry O
( O
NPR O
) O
by O
comparison O
with O
patient O
medical O
records O
. O
Patients O
and O
methods O
Men O
and O
women O
in O
the O
Diet O
, O
Cancer O
and O
Health O
( O
DCH O
) O
cohort O
were O
linked O
to O
NPR O
, O
and O
cases O
with O
a O
diagnosis O
of O
IBD O
and O
their O
respective O
hospital O
records O
were O
identified O
. O
Validation O
was O
performed O
by O
comparing O
patient O
medical O
records O
with O
information O
on O
discharge O
diagnoses O
of O
IBD O
from O
the O
NPR O
. O
Results O
Of O
57,053 O
individuals O
in O
the O
DCH O
- O
cohort O
, O
339 O
were O
registered O
with O
an O
IBD O
diagnosis O
in O
NPR O
, O
with O
277 B-STAT
( O
82 O
% O
) O
records O
available O
for O
review O
. O
Among O
277 O
patients O
, O
the O
positive O
predictive O
values O
( O
PPVs O
) O
of O
one O
CD O
or O
UC O
registration O
in O
NPR O
were O
78 O
% O
for O
IBD O
overall O
, O
51 O
% O
for O
CD O
and O
54 O
% O
for O
UC O
. O
One O
hundred O
fifty O
- O
seven O
patients O
had O
at O
least O
two O
CD O
and/or O
UC O
registrations O
with O
PPVs O
of O
90 O
% O
for O
IBD O
overall O
, O
65 O
% O
for O
CD O
and O
73 O
% O
for O
UC O
. O
One O
hundred O
and O
two O
patients O
had O
at O
least O
three O
registrations O
with O
PPVs O
of O
97 O
% O
for O
IBD O
overall O
, O
75 O
% O
for O
CD O
and O
88 O
% O
for O
UC O
. O
96 B-STAT
% I-STAT
were O
diagnosed O
at O
a O
specialized O
department O
. O
Other O
diagnoses O
coded O
as O
IBD O
mostly O
included O
microscopic O
colitis O
, O
irritable O
bowel O
syndrome O
and O
cancer O
. O
Conclusion O
Validity O
of O
IBD O
diagnoses O
in O
the O
registry O
of O
individuals O
aged O
50 O
+ O
years O
increased O
with O
the O
number O
of O
registrations O
. O
It O
is O
recommended O
that O
these O
results O
are O
taken O
into O
consideration O
in O
future O
studies O
, O
especially O
in O
epidemiology O
research O
using O
NPR O
as O
a O
data O
source O
for O
patients O
diagnosed O
with O
IBD O
. O
Purpose O
To O
determine O
if O
there O
is O
an O
increased O
incidence B-EPI
rate O
of O
post O
- O
cataract O
surgery O
( O
pcs O
) O
anterior O
ischemic O
optic O
neuropathy O
( O
AION O
) O
compared O
to O
spontaneous O
AION O
( O
sAION O
) O
. O
Design O
Retrospective O
, O
population O
- O
based O
cohort O
. O
Methods O
Patients O
diagnosed O
with O
AION O
from O
January O
1 O
, O
1990 O
, O
through O
December O
31 O
, O
2016 O
, O
while O
residing O
in O
Olmsted B-LOC
County I-LOC
, O
Minnesota B-LOC
. O
Patients O
with O
cataract O
surgery O
preceding O
AION O
were O
included O
in O
the O
pcsAION O
cohort O
defined O
in O
2 O
ways O
: O
AION O
within O
2 O
months O
and O
AION O
within O
1 B-STAT
year I-STAT
of O
cataract O
surgery O
. O
The O
incidence B-EPI
rates O
of O
pcsAION B-LOC
and O
sAION O
were O
compared O
using O
Poisson O
regression O
models O
. O
Results O
During O
the O
study O
period O
, O
102 O
residents O
developed O
AION O
. O
The O
median O
age O
was O
65 O
years O
( O
range O
, O
40 O
- O
90 O
years O
) O
, O
44 B-STAT
( O
43.1 O
% O
) O
were O
female O
. O
Twenty O
of O
102 B-STAT
( O
19.6 O
% O
) O
patients O
had O
previous O
cataract O
surgery O
, O
of O
which O
2 O
and O
9 O
developed O
AION O
within O
2 O
months O
and O
1 B-STAT
year I-STAT
of O
surgery O
, O
respectively O
. O
The O
annual B-EPI
incidence I-EPI
rate O
of O
pcsAION O
within O
2 O
months O
of O
surgery O
( O
8.6 B-STAT
per I-STAT
100,000 I-STAT
) I-STAT
was O
not O
significantly O
greater O
than O
the O
annual B-EPI
incidence I-EPI
rate O
of O
sAION O
( O
6.9 B-STAT
per I-STAT
100,000 I-STAT
; I-STAT
P O
= O
.78 O
) O
. O
However O
, O
the O
annual B-EPI
incidence I-EPI
rate O
of O
pcsAION B-LOC
within O
1 O
year O
of O
surgery O
( O
38.9 B-STAT
per I-STAT
100,000 I-STAT
) I-STAT
was O
significantly O
higher O
than O
the O
incidence B-EPI
rate O
of O
sAION O
( O
6.5 B-STAT
per I-STAT
100,000 I-STAT
; I-STAT
P O
< O
.001 O
) O
. O
Conclusion O
The O
incidence B-EPI
of O
AION O
is O
increased O
in O
the O
first O
year O
after O
cataract O
surgery O
, O
but O
not O
in O
the O
early O
( O
i.e. O
, O
2 O
months O
) O
postoperative O
period O
. O
Talaromyces O
marneffei O
causes O
life O
- O
threatening O
opportunistic O
infections O
, O
mainly O
in O
Southeast B-LOC
Asia I-LOC
and O
South B-LOC
China I-LOC
. O
T. O
marneffei O
mainly O
infects O
patients O
with O
human O
immunodeficiency O
virus O
( O
HIV O
) O
but O
also O
infects O
individuals O
without O
known O
immunosuppression O
. O
Here O
we O
investigated O
the O
involvement O
of O
anti O
- O
IFN O
- O
γ O
autoantibodies O
in O
severe O
T. O
marneffei O
infections O
in O
HIV O
- O
negative O
patients O
. O
We O
enrolled O
58 O
HIV O
- O
negative O
adults O
with O
severe O
T. O
marneffei O
infections O
who O
were O
otherwise O
healthy O
. O
We O
found O
a O
high O
prevalence B-EPI
of O
neutralizing O
anti O
- O
IFN O
- O
γ O
autoantibodies O
( O
94.8 O
% O
) O
in O
this O
cohort O
. O
The O
presence O
of O
anti O
- O
IFN O
- O
γ O
autoantibodies O
was O
strongly O
associated O
with O
HLA O
- O
DRB1 O
* O
16:02 O
and O
-DQB1 O
* O
05:02 O
alleles O
in O
these O
patients O
. O
We O
demonstrated O
that O
adult O
- O
onset O
acquired O
immunodeficiency O
due O
to O
autoantibodies O
against O
IFN O
- O
γ O
is O
the O
major O
cause O
of O
severe O
T. O
marneffei O
infections O
in O
HIV O
- O
negative O
patients O
in O
regions O
where O
this O
fungus O
is O
endemic O
. O
The O
high O
prevalence B-EPI
of O
anti O
- O
IFN O
- O
γ O
autoantibody O
- O
associated O
HLA O
class O
II O
DRB1 O
* O
16:02 O
and O
DQB1 O
* O
05:02 O
alleles O
may O
account O
for O
severe O
T. O
marneffei O
infections O
in O
Southeast B-LOC
Asia I-LOC
. O
Our O
findings O
clarify O
the O
pathogenesis O
of O
T. O
marneffei O
infection O
and O
pave O
the O
way O
for O
developing O
novel O
treatments O
. O
Congenital O
hypothyroidism O
( O
CH O
) O
is O
a O
highly O
prevalent B-EPI
but O
treatable O
neonatal O
endocrine O
disorder O
. O
Thyroid O
dyshormonogenesis O
is O
the O
main O
cause O
of O
congenital O
hypothyroidism O
in O
Chinese O
CH O
patients O
, O
and O
DUOX2 O
is O
the O
most O
frequent O
mutated O
gene O
involved O
in O
H2O2 O
production O
. O
In O
humans O
, O
the O
primary O
sources O
for O
H2O2 O
production O
are O
DUOX1 O
and O
DUOX2 O
, O
while O
in O
zebrafish O
there O
is O
only O
a O
single O
orthologue O
for O
DUOX1 O
and O
DUOX2 B-LOC
. O
In O
this O
study O
, O
duox O
mutant O
zebrafish O
were O
generated O
through O
knockdown O
duox O
by O
morpholino O
or O
knockout O
duox O
by O
CRISPR O
Cas9 O
. O
The O
associated O
phenotypes O
were O
investigated O
and O
rescued O
by O
thyroxine O
( O
T4 O
) O
treatment O
. O
Mutant O
zebrafish O
displayed O
hypothyroid O
phenotypes O
including O
growth O
retardation O
, O
goiter O
and O
, O
infertility O
. O
Homozygous O
mutants O
in O
adults O
also O
displayed O
extrathyroidal O
abnormal O
phenotypes O
, O
including O
lacking O
barbels O
, O
pigmentation O
defects O
, O
erythema O
in O
the O
opercular O
region O
, O
ragged O
fins O
, O
and O
delayed O
scales O
. O
All O
these O
abnormal O
phenotypes O
can O
be O
rescued O
by O
10 O
nM O
T4 O
treatment O
. O
Strikingly O
, O
the O
fertility O
of O
zebrafish O
was O
dependent O
on O
thyroid O
hormone O
; O
T4 O
treatment O
should O
be O
continued O
and O
can O
not O
be O
stopped O
over O
2 O
weeks O
in O
hypothyroid O
zebrafish O
in O
order O
to O
achieve O
fertility O
. O
Thyroid O
hormones O
played O
a O
role O
in O
the O
developing O
and O
maturing O
of O
reproductive O
cells O
. O
Our O
work O
indicated O
that O
duox O
mutant O
zebrafish O
may O
provide O
a O
model O
for O
human O
congenital O
hypothyroidism O
. O
Context O
Aggrecan O
, O
encoded O
by O
the O
ACAN O
gene O
, O
is O
the O
main O
proteoglycan O
component O
in O
the O
extracellular O
cartilage O
matrix O
. O
Heterozygous O
mutations O
in O
ACAN O
have O
been O
reported O
to O
cause O
idiopathic O
short O
stature O
. O
However O
, O
the O
prevalence B-EPI
of O
ACAN O
pathogenic O
variants O
in O
Chinese O
short O
stature O
patients O
and O
clinical O
phenotypes O
remain O
to O
be O
evaluated O
. O
Objective O
We O
sought O
to O
determine O
the O
prevalence B-EPI
of O
ACAN O
pathogenic O
variants O
among O
Chinese O
short O
stature O
children O
and O
characterize O
the O
phenotypic O
spectrum O
and O
their O
responses O
to O
growth O
hormone O
therapies O
. O
Patients O
and O
methods O
Over O
1000 O
unrelated O
short O
stature O
patients O
ascertained O
across O
China B-LOC
were O
genetically O
evaluated O
by O
next O
- O
generation O
sequencing O
- O
based O
test O
. O
Result O
We O
identified O
10 O
novel O
likely O
pathogenic O
variants O
and O
2 O
recurrent O
pathogenic O
variants O
in O
this O
cohort O
. O
None O
of O
ACAN O
mutation O
carriers O
exhibited O
significant O
dysmorphic O
features O
or O
skeletal O
abnormities O
. O
The O
prevalence B-EPI
of O
ACAN O
defect O
is O
estimated O
to O
be O
1.2 O
% O
in O
the O
whole O
cohort O
; O
it O
increased B-STAT
to O
14.3 O
% O
among O
those O
with O
advanced O
bone O
age O
and O
to O
35.7 B-STAT
% O
among O
those O
with O
both O
advanced O
bone O
age O
and O
family O
history O
of O
short O
stature O
. O
Nonetheless O
, O
5 O
of O
11 O
ACAN O
mutation O
carries O
had O
no O
advanced O
bone O
age O
. O
Two O
individuals O
received O
growth O
hormone O
therapy O
with O
variable O
levels O
of O
height O
SD O
score O
improvement O
. O
Conclusion O
Our O
data O
suggest O
that O
ACAN O
mutation O
is O
1 O
of O
the O
common O
causes O
of O
Chinese O
pediatric O
short O
stature O
. O
Although O
it O
has O
a O
higher O
detection O
rate O
among O
short O
stature O
patients O
with O
advanced O
bone O
age O
and O
family O
history O
, O
part O
of O
affected O
probands O
presented O
with O
delayed O
bone O
age O
in O
Chinese O
short O
stature O
population O
. O
The O
growth O
hormone O
treatment O
was O
moderately O
effective O
for O
both O
individuals O
. O
Purpose O
The O
aim O
of O
this O
study O
was O
to O
review O
patients O
with O
xanthogranulomatous O
cholecystitis O
( O
XGC O
) O
. O
Methods O
A O
total O
of O
79 O
patients O
diagnosed O
with O
XGC O
were O
included O
in O
the O
study O
. O
The O
criteria O
for O
XGC O
in O
the O
pathology O
specimens O
were O
the O
presence O
of O
histiocytes O
, O
cholesterol O
deposits O
, O
lipids O
, O
and O
focal O
or O
widespread O
wall O
enlargement O
. O
Results O
Patients O
were O
diagnosed O
with O
XGC O
, O
of O
which O
52 B-STAT
( O
65.8 O
% O
) O
were O
male O
and O
27 B-STAT
( O
34.2 O
% O
) O
were O
female O
, O
creating O
a O
male O
- O
to O
- O
female O
ratio O
of O
2:1 O
. O
The O
mean O
age O
was O
65.8 O
± O
14.3 O
years O
( O
range O
, O
36 O
- O
97 O
years O
) O
. O
The O
most O
common O
presenting O
symptom O
was O
abdominal O
pain O
( O
63.3 O
% O
) O
, O
and O
the O
least O
common O
presenting O
symptom O
was O
jaundice O
( O
8.9 O
% O
) O
. O
Of O
the O
total O
, O
25 O
patients O
were O
found O
to O
have O
pathological O
conditions O
with O
the O
potential O
to O
obstruct O
the O
bile O
duct O
or O
to O
slow O
bile O
flow O
. O
A O
frozen O
section O
examination O
was O
performed O
on O
20 O
patients O
due O
to O
suspicion O
of O
a O
tumor O
by O
intraoperative O
macroscopic O
examination O
. O
However O
, O
no O
malignancy O
was O
detected O
in O
the O
cases O
who O
underwent O
a O
frozen O
section O
examination O
. O
An O
increase O
in O
wall O
thickness O
of O
the O
gallbladder O
was O
observed O
in O
81.6 O
% O
( O
n O
= O
31 O
) O
of O
the O
patients O
on O
computed O
tomography O
scans O
and O
in O
81.8 O
% O
( O
n O
= O
18 O
) O
of O
the O
patients O
on O
magnetic O
resonance O
imaging O
scans O
in O
which O
possible O
tumor O
lesions O
were O
reported O
, O
but O
no O
tumor O
was O
detected O
. O
Conclusion O
It O
is O
difficult O
to O
diagnose O
XGC O
either O
preoperatively O
or O
intraoperatively O
, O
and O
further O
imaging O
methods O
are O
needed O
in O
the O
preoperative O
period O
other O
than O
ultrasonography O
. O
However O
, O
a O
definitive O
diagnosis O
depends O
exclusively O
on O
pathologic O
examination O
. O
Adrenocortical O
carcinoma O
( O
ACC O
) O
is O
a O
rare O
endocrine O
malignancy O
arising O
from O
the O
adrenal O
cortex O
often O
with O
unexpected O
biological O
behavior O
. O
It O
can O
occur O
at O
any O
age O
, O
with O
two O
peaks O
of O
incidence B-EPI
: O
in O
the O
first O
and O
between O
fifth O
and O
seventh O
decades O
of O
life O
. O
Although O
ACC O
are O
mostly O
hormonally O
active O
, O
precursors O
and O
metabolites O
, O
rather O
than O
end O
products O
of O
steroidogenesis O
are O
produced O
by O
dedifferentiated O
and O
immature O
malignant O
cells O
. O
Distinguishing O
the O
etiology O
of O
adrenal O
mass O
, O
between O
benign O
adenomas O
, O
which O
are O
quite O
frequent O
in O
general O
population O
, O
and O
malignant O
carcinomas O
with O
dismal O
prognosis O
is O
often O
unfeasible O
. O
Even O
after O
pathohistological O
analysis O
, O
diagnosis O
of O
adrenocortical O
carcinomas O
is O
not O
always O
straightforward O
and O
represents O
a O
great O
challenge O
for O
experienced O
and O
multidisciplinary O
expert O
teams O
. O
No O
single O
imaging O
method O
, O
hormonal O
work O
- O
up O
or O
immunohistochemical O
labelling O
can O
definitively O
prove O
the O
diagnosis O
of O
ACC O
. O
Over O
several O
decades O
' O
great O
efforts O
have O
been O
made O
in O
finding O
novel O
reliable O
and O
available O
diagnostic O
and O
prognostic O
factors O
including O
steroid O
metabolome O
profiling O
or O
target O
gene O
identification O
. O
Despite O
these O
achievements O
, O
the O
5 O
- O
year O
mortality O
rate O
still O
accounts O
for O
approximately O
75 O
% O
to O
90 O
% O
, O
ACC O
is O
frequently O
diagnosed O
in O
advanced O
stages O
and O
therapeutic O
options O
are O
unfortunately O
limited O
. O
Therefore O
, O
imperative O
is O
to O
identify O
new O
biological O
markers O
that O
can O
predict O
patient O
prognosis O
and O
provide O
new O
therapeutic O
options O
. O
Background O
Kindler O
poikiloderma O
is O
an O
inherited O
autosomal O
genodermatosis O
characterized O
by O
blistering O
of O
the O
epidermis O
and O
mucosae O
. O
Its O
prevalence B-EPI
is O
unknown O
. O
Case O
report O
We O
monitored O
two O
brothers O
suffering O
from O
this O
pathology O
. O
Oral O
manifestations O
mainly O
take O
the O
form O
of O
periodontal O
lesions O
. O
In O
our O
patients O
we O
noted O
gingivitis O
progressing O
to O
periodontitis O
as O
follow O
- O
up O
care O
was O
not O
effective O
. O
We O
also O
diagnosed O
enamel O
hypoplasia O
, O
described O
more O
rarely O
in O
this O
pathology O
. O
Conclusion O
Periodontitis O
in O
Kindler O
Syndrome O
responds O
to O
maintenance O
therapy O
, O
but O
the O
absence O
of O
surveillance O
is O
penalized O
by O
a O
deterioration O
in O
periodontal O
condition O
and O
complication O
of O
management O
. O
All O
restorative O
, O
endodontic O
, O
surgical O
, O
periodontal O
and O
orthodontic O
treatments O
should O
be O
performed O
with O
appropriate O
precautions O
. O
Background O
Several O
studies O
have O
shown O
a O
high O
rate O
of O
consanguinity O
and O
endogamy O
in O
North O
African O
populations O
. O
As O
a O
result O
, O
the O
frequency O
of O
autosomal O
recessive O
diseases O
is O
relatively O
high O
in O
the O
region O
with O
the O
co O
- O
occurrence B-EPI
of O
two O
or O
more O
diseases O
. O
Methods O
We O
report O
here O
on O
a O
consanguineous O
Libyan O
family O
whose O
child O
was O
initially O
diagnosed O
as O
presenting O
Fanconi O
anemia O
( O
FA O
) O
with O
uncommon O
skeletal O
deformities O
. O
The O
chromosome O
breakage O
test O
has O
been O
performed O
using O
mitomycin O
C O
( O
MMC O
) O
while O
molecular O
analysis O
was O
performed O
by O
a O
combined O
approach O
of O
linkage O
analysis O
and O
whole O
exome O
sequencing O
. O
Results O
Cytogenetic O
analyses O
showed O
that O
the O
karyotype O
of O
the O
female O
patient O
is O
46,XY O
suggesting O
the O
diagnosis O
of O
a O
disorder O
of O
sex O
development O
( O
DSD O
) O
. O
By O
looking O
at O
the O
genetic O
etiology O
of O
FA O
and O
DSD O
, O
we O
have O
identified O
p.[Arg798*];[Arg798 O
* O
] O
mutation O
in O
FANCJ O
( O
OMIM O
# O
605882 O
) O
gene O
responsible O
for O
FA O
and O
p.[Arg108*];[Arg1497Trp O
] O
in O
EFCAB6 O
( O
Gene O
# O
64800 O
) O
gene O
responsible O
for O
DSD O
. O
In O
addition O
, O
we O
have O
incidentally O
discovered O
a O
novel O
mutation O
p.[Gly1372Arg];[Gly1372Arg O
] O
in O
the O
ERCC6 O
( O
CSB O
) O
( O
OMIM O
# O
609413 O
) O
gene O
responsible O
for O
COFS O
that O
might O
explain O
the O
atypical O
severe O
skeletal O
deformities O
. O
Conclusion O
The O
co O
- O
occurrence B-EPI
of O
clinical O
and O
overlapping O
genetic O
heterogeneous O
entities O
should O
be O
taken O
into O
consideration O
for O
better O
molecular O
and O
genetic O
counseling O
. O
Pyridoxine O
- O
dependent O
epilepsy O
( O
PDE O
) O
is O
a O
potentially O
treatable O
vitamin O
- O
responsive O
epileptic O
encephalopathy O
. O
The O
most O
prevalent B-EPI
form O
of O
PDE O
is O
due O
to O
an O
underlying O
genetic O
defect O
in O
ALDH7A1 O
encoding O
Antiquitin O
( O
ATQ O
) O
, O
an O
enzyme O
with O
α O
- O
aminoadipic O
semialdehyde O
dehydrogenase O
( O
AASADH O
) O
activity O
which O
facilitates O
cerebral O
lysine O
degradation O
. O
Devastating O
outcomes O
including O
intellectual O
disability O
and O
significant O
developmental O
delays O
are O
still O
observed O
in O
75 O
% O
to O
80 O
% O
of O
pyridoxine O
responsive O
individuals O
with O
good O
seizure O
control O
, O
potentially O
attributable O
to O
the O
accumulation O
of O
toxic O
intermediates O
α O
- O
aminoadipic O
semialdehyde O
( O
AASA O
) O
and O
its O
cyclic O
form O
Δ O
1 O
-piperideine-6 O
- O
carboxylate O
( O
P6C O
) O
in O
plasma O
, O
urine O
and O
CSF O
. O
Thus O
, O
adjunct O
treatment O
strategies O
incorporating O
lysine O
restriction O
and O
arginine O
supplementation O
, O
separately O
or O
in O
combination O
with O
pyridoxine O
have O
been O
attempted O
to O
enhance O
seizure O
control O
and O
improve O
cognitive O
function O
. O
We O
describe O
a O
4 O
year O
old O
girl O
with O
classical O
PDE O
who O
demonstrated O
significant O
improvements O
in O
clinical O
, O
neurological O
and O
developmental O
outcomes O
including O
absence O
of O
clinical O
seizures O
and O
cessation O
of O
antiepileptic O
medications O
since O
age O
3 O
months O
, O
normalisation O
of O
EEG O
, O
significant O
improvement O
in O
the O
white O
matter O
signal O
throughout O
the O
cerebrum O
on O
neuroimaging O
and O
significant O
reduction O
in O
urine O
P6C O
and O
pipecolic O
acid O
levels O
post- O
combined O
therapy O
with O
lysine O
restricted O
diet O
in O
conjunction O
with O
pyridoxine O
and O
folinic O
acid O
. O
Lysine O
restriction O
was O
well O
tolerated O
with O
impressive O
compliance O
and O
plasma O
lysine O
levels O
remained O
within O
the O
lower O
reference O
ranges O
; O
mean O
level O
70 O
μmol O
/ O
L O
( O
ref O
range O
52 O
- O
196 O
μmol O
/ O
L O
) O
. O
This O
case O
further O
emphasizes O
the O
benefit O
of O
early O
dietary O
intervention O
as O
an O
effective O
adjunct O
in O
the O
management O
of O
PDE O
. O
Neonatal O
herpes O
simplex O
virus O
infection O
( O
HSV O
) O
is O
rare O
in O
neonates O
, O
with O
an O
estimated O
global B-LOC
incidence B-EPI
of O
10 B-STAT
per I-STAT
100,000 I-STAT
live I-STAT
births I-STAT
. O
Neonatal O
HSV O
is O
challenging O
to O
diagnose O
due O
to O
often O
vague O
signs O
and O
symptoms O
. O
Untreated O
, O
the O
mortality O
of O
some O
HSV O
subtypes O
exceeds O
80 B-STAT
% I-STAT
. O
Overtesting O
and O
overtreatment O
can O
result O
in O
prolonged O
hospitalizations O
and O
expose O
neonates O
to O
medication O
toxicity O
. O
In O
contrast O
, O
prompt O
evaluation O
and O
use O
of O
empiric O
antiviral O
therapy O
before O
the O
results O
of O
definitive O
testing O
can O
improve O
outcomes O
for O
infants O
with O
HSV O
. O
A O
wide O
degree O
of O
practice O
variation O
exists O
with O
respect O
to O
testing O
and O
treatment O
for O
neonatal O
HSV O
, O
and O
more O
research O
is O
required O
to O
safely O
risk O
- O
stratify O
this O
population O
. O
This O
review O
presents O
the O
epidemiology O
, O
risk O
factors O
, O
presenting O
features O
, O
and O
emergency O
department O
management O
of O
neonatal O
HSV O
infection O
. O
Since O
it O
was O
first O
documented O
in O
1948 O
by O
Sir O
William O
Heneage O
Ogilvie O
, O
numerous O
cases O
of O
Ogilvie O
syndrome O
have O
been O
described O
in O
literature O
due O
to O
various O
medical O
and O
surgical O
causes O
. O
Nonetheless O
, O
only O
a O
handful O
of O
cases O
only O
have O
been O
documented O
due O
to O
underlying O
Acquired O
Immunodeficiency O
Syndrome O
( O
AIDS O
) O
. O
A O
41 O
- O
year O
- O
old O
female O
was O
admitted O
with O
an O
acute O
abdomen O
secondary O
to O
partial O
mechanical O
intestinal O
obstruction O
or O
paralytic O
ileus O
based O
on O
signs O
and O
symptoms O
and O
Abdominal O
X O
- O
Ray O
( O
AXR O
) O
. O
She O
was O
known O
to O
be O
HIV O
/ O
AIDS O
WHO O
clinical O
stage O
II O
on O
treatment O
. O
On O
diagnostic O
imaging O
studies O
she O
had O
distended O
large O
bowels O
without O
features O
of O
mechanical O
intestinal O
obstruction O
and O
the O
diagnosis O
of O
Ogilvie O
syndrome O
was O
suspected O
after O
other O
differentials O
were O
excluded O
. O
Early O
recognition O
and O
appropriate O
management O
are O
essential O
, O
because O
if O
left O
untreated O
the O
bowel O
distension O
may O
progress O
to O
caecal O
perforation O
and O
fatal O
peritonitis O
. O
Medical O
imaging O
with O
Computer O
Tomography O
( O
CT O
) O
scan O
and O
colonoscopy O
has O
helped O
in O
achieving O
an O
accurate O
diagnosis O
and O
avoiding O
unnecessary O
laparotomies O
. O
Although O
an O
uncommon O
disorder O
, O
for O
earlier O
and O
accurate O
diagnosis O
a O
high O
index O
of O
suspicion O
is O
required O
by O
clinicians O
and O
radiologists O
who O
are O
treating O
patients O
with O
underlying O
HIV O
/ O
AIDS O
. O
Ogilvie O
's O
syndrome O
is O
a O
rare O
condition O
and O
if O
missed O
can O
be O
fatal O
. O
In O
patients O
with O
HIV O
/ O
AIDS O
, O
the O
symptoms O
may O
be O
directly O
due O
to O
HIV O
infection O
, O
secondary O
to O
opportunistic O
infections O
or O
possible O
neurotoxic O
effects O
of O
HIV O
treatment O
or O
lack O
of O
vitamin O
and O
minerals O
. O
It O
is O
important O
to O
exclude O
Ogilvie O
syndrome O
in O
patients O
from O
surgical O
causes O
of O
the O
acute O
abdomen O
to O
avoid O
unnecessary O
surgical O
procedures O
. O
Pathogenic O
variants O
in O
the O
fibroblast O
growth O
factor O
receptor O
3 O
( O
FGFR3 O
) O
gene O
are O
responsible O
for O
a O
broad O
spectrum O
of O
skeletal O
dysplasias O
, O
including O
achondroplasia O
( O
ACH O
) O
. O
The O
classic O
phenotype O
of O
ACH O
is O
caused O
by O
two O
highly O
prevalent B-EPI
mutations O
, O
c.1138 O
G O
> O
A O
and O
c.1138 O
G O
> O
C O
( O
p. O
Gly380Arg O
) O
. O
In O
the O
homozygous O
state O
, O
these O
variant O
results O
in O
a O
severe O
skeletal O
dysplasia O
, O
neurologic O
deficits O
, O
and O
early O
demise O
from O
respiratory O
insufficiency O
. O
Although O
homozygous O
biallelic O
mutations O
have O
been O
reported O
in O
patients O
with O
ACH O
in O
combination O
with O
hypochondroplasia O
or O
other O
dominant O
skeletal O
dysplasias O
, O
thus O
far O
, O
no O
cases O
of O
heterozygous O
biallelic O
pathogenic O
ACH O
- O
related O
variants O
in O
FGFR3 O
have O
been O
reported O
. O
We O
describe O
a O
novel O
phenotype O
of O
an O
infant O
with O
two O
ACH O
- O
related O
mutations O
in O
FGFR3 O
, O
p. O
Gly380Arg O
and O
p. O
Ser344Cys O
. O
Discordant O
features O
from O
classic O
ACH O
include O
atypical O
radiographic O
findings O
, O
severe O
obstructive O
sleep O
apnea O
, O
and O
focal O
, O
migrating O
seizures O
. O
We O
also O
report O
the O
long O
- O
term O
clinical O
course O
of O
her O
father O
, O
who O
harbors O
the O
p. O
Ser344Cys O
mutation O
that O
has O
only O
been O
reported O
once O
previously O
in O
a O
Japanese O
patient O
. O
The O
phenotype O
of O
heterozygous O
biallelic O
mutations O
in O
FGFR3 O
associated O
with O
ACH O
is O
variable O
, O
underscoring O
the O
importance O
of O
recognition O
and O
accurate O
diagnosis O
to O
ensure O
appropriate O
management O
. O
The O
temperate O
United B-LOC
States I-LOC
has O
experienced O
increasing O
incidence B-EPI
of O
mosquito O
- O
borne O
diseases O
. O
Recent O
studies O
conducted O
in O
Baltimore B-LOC
, O
MD B-LOC
have O
demonstrated O
a O
negative O
relationship O
between O
abundances O
of O
Aedes O
albopictus O
( O
Skuse O
) O
and O
Culex O
mosquitoes O
and O
mean O
neighborhood O
income O
level O
, O
but O
have O
not O
looked O
at O
the O
presence O
of O
pathogens O
. O
Mosquitoes O
collected O
from O
five O
socioeconomically O
variable O
neighborhoods O
were O
tested O
for O
infection O
by O
West B-LOC
Nile I-LOC
, O
chikungunya O
, O
and O
Zika O
viruses O
in O
2015 O
and O
2016 O
, O
and O
again O
from O
four O
of O
the O
neighborhoods O
in O
2017 O
. O
Minimum O
infection O
rates O
of O
pooled O
samples O
were O
compared O
among O
neighborhoods O
for O
each O
year O
, O
as O
well O
as O
among O
individual O
blocks O
in O
2017 O
. O
West B-LOC
Nile I-LOC
virus O
was O
detected O
in O
both O
Ae O
. O
albopictus O
and O
Culex O
pools O
from O
all O
neighborhoods O
sampled O
in O
2015 O
and O
2017 O
. O
No O
infected O
pools O
were O
detected O
in O
any O
year O
for O
chikungunya O
or O
Zika O
viruses O
, O
and O
none O
of O
the O
target O
viruses O
were O
detected O
in O
2016 O
. O
Infection O
rates O
were O
consistently O
higher O
for O
Culex O
than O
for O
Ae O
. O
albopictus O
. O
Minimum O
infection O
rate O
was O
negatively O
associated O
with O
mean O
neighborhood O
income O
for O
both O
species O
in O
2015 O
. O
Although O
earlier O
work O
has O
shown O
a O
positive O
association O
between O
block O
- O
level O
abandonment O
and O
mosquito O
abundance O
, O
no O
association O
was O
detected O
in O
this O
study O
. O
Still O
, O
we O
demonstrate O
that O
viral O
infection O
in O
mosquito O
pools O
can O
differ O
substantially O
across O
adjacent O
urban O
neighborhoods O
that O
vary O
by O
income O
. O
Though O
trap O
security O
and O
accessibility O
often O
inform O
city O
sampling O
locations O
, O
detecting O
and O
managing O
arboviral O
risk O
requires O
surveillance O
across O
neighborhoods O
that O
vary O
in O
socioeconomics O
, O
including O
lower O
income O
areas O
that O
may O
be O
less O
accessible O
and O
secure O
but O
have O
higher O
infection O
rates O
. O
Li O
- O
Fraumeni O
syndrome O
( O
LFS O
) O
is O
an O
inherited O
cancer O
syndrome O
, O
characterized O
by O
an O
early O
onset O
of O
various O
types O
of O
cancers O
. O
LFS O
is O
associated O
with O
a O
germline O
mutation O
in O
the O
TP53 O
gene O
. O
The O
risk O
of O
developing O
skin O
cancer O
in O
patients O
with O
LFS O
is O
unknown O
. O
To O
evaluate O
the O
cumulative O
risk O
of O
skin O
cancer O
in O
patients O
with O
LFS O
and O
to O
compare O
this O
risk O
to O
the O
general O
Dutch O
population O
. O
In O
this O
retrospective O
cohort O
study O
, O
all O
proven O
TP53 O
mutation O
carriers O
in O
the O
Netherlands O
Cancer O
Institute O
were O
included O
from O
their O
first O
visit O
to O
the O
Institute O
until O
June O
2017 O
. O
Medical O
charts O
and O
pathology O
reviews O
cross O
- O
referenced O
with O
PALGA O
, O
the O
nationwide O
network O
and O
registry O
of O
histo- O
and O
cytopathology O
were O
used O
to O
identify O
incident O
skin O
cancers O
. O
Cumulative O
risks O
were O
calculated O
by O
Kaplan O
- O
Meier O
analysis O
. O
Seventy B-STAT
- I-STAT
one I-STAT
patients I-STAT
( O
59 O
% O
female O
) O
from O
33 O
families O
were O
included O
. O
Ten O
patients O
( O
14 O
% O
) O
developed O
a O
total O
of O
19 O
skin O
cancers O
at O
a O
median O
age O
of O
41 O
( O
25 O
- O
65 O
) O
years O
. O
The O
cumulative O
risk O
of O
skin O
cancer O
is O
10.4 O
% O
( O
95 O
% O
CI O
4.4 O
- O
23.5 O
% O
) O
at O
age O
40 B-STAT
, O
25.2 O
% O
( O
95 O
% O
CI O
12.3 O
- O
47.6 O
% O
) O
at O
age O
60 O
, O
and O
a O
at O
age O
70 O
this O
risk O
is O
44.6 O
% O
( O
95 O
% O
CI O
22.9 O
- O
73.9 O
% O
) O
. O
The O
cumulative O
risks O
of O
melanoma O
and O
basal O
cell O
carcinoma O
at O
age O
70 O
are O
increased O
compared O
to O
the O
general O
Dutch O
population O
, O
namely O
12.6 O
% O
( O
95 O
% O
CI O
3.6 O
- O
38.4 O
% O
) O
and O
34.6 O
% O
( O
95 O
% O
CI O
15.4 O
- O
66.2 O
% O
) O
, O
respectively O
. O
Patients O
with O
LFS O
have O
an O
increased O
risk O
of O
developing O
skin O
cancer O
. O
A O
dermatological O
consultation O
may O
be O
considered O
at O
least O
once O
in O
individuals O
with O
LFS O
to O
raise O
awareness O
for O
skin O
cancer O
and O
inform O
about O
risk O
factors O
. O
Background O
Intestinal O
malrotation O
is O
a O
potentially O
life O
- O
threatening O
congenital O
anomaly O
due O
to O
the O
risk O
of O
developing O
midgut O
volvulus O
. O
The O
reported O
incidence B-EPI
is O
0.2%-1 B-STAT
% I-STAT
and O
both O
apparently O
hereditary O
and O
sporadic O
cases O
have O
been O
reported O
. O
Intestinal O
malrotation O
is O
associated O
with O
a O
few O
syndromes O
with O
known O
genotype O
but O
the O
genetic O
contribution O
in O
isolated O
intestinal O
malrotation O
has O
not O
yet O
been O
reported O
. O
Rare O
copy O
number O
variants O
( O
CNVs O
) O
have O
been O
implicated O
in O
many O
congenital O
anomalies O
, O
and O
hence O
we O
sought O
to O
investigate O
the O
potential O
contribution O
of O
rare O
CNVs O
in O
intestinal O
malrotation O
. O
Methods O
Analysis O
of O
array O
comparative O
genomic O
hybridization O
( O
aCGH O
) O
data O
from O
47 O
patients O
with O
symptomatic O
intestinal O
malrotation O
was O
performed O
. O
Results O
We O
identified O
six O
rare O
CNVs O
in O
five O
patients O
. O
Five O
CNVs O
involved O
syndrome O
loci O
: O
7q11.23 O
microduplication O
, O
16p13.11 O
microduplication O
, O
18q O
terminal O
deletion O
, O
HDAC8 O
( O
Cornelia O
de O
Lange O
syndrome O
type O
5 O
and O
FOXF1 O
) O
as O
well O
as O
one O
intragenic O
deletion O
in O
GALNT14 O
, O
not O
previously O
implicated O
in O
human O
disease O
. O
Conclusion O
In O
the O
present O
study O
, O
we O
identified O
rare O
CNVs O
contributing O
pathogenic O
or O
potentially O
pathogenic O
alleles O
in O
five O
patients O
with O
syndromic O
intestinal O
malrotation O
, O
suggesting O
that O
CNV O
screening O
is O
indicated O
in O
intestinal O
malrotation O
with O
associated O
malformations O
or O
neurological O
involvements O
. O
In O
addition O
, O
we O
identified O
intestinal O
malrotation O
in O
two O
known O
syndromes O
( O
Cornelia O
de O
Lange O
type O
5 O
and O
18q O
terminal O
deletion O
syndrome O
) O
that O
has O
not O
previously O
been O
associated O
with O
gastrointestinal O
malformations O
. O
Since O
the O
discovery O
of O
human O
leukocyte O
antigens O
( O
HLAs O
) O
, O
the O
function O
of O
major O
histocompatibility O
complex O
( O
MHC O
) O
gene O
families O
in O
a O
wide O
range O
of O
diseases O
have O
been O
the O
subject O
of O
research O
for O
decades O
. O
In O
particular O
, O
the O
associations O
of O
autoimmune O
disorders O
to O
allelic O
variants O
and O
candidate O
genes O
encoding O
the O
MHC O
are O
well O
documented O
. O
However O
, O
despite O
decades O
of O
research O
, O
the O
knowledge O
of O
MHC O
associations O
with O
human O
disease O
susceptibility O
have O
been O
predominantly O
studied O
in O
European O
origin O
, O
with O
limited O
understanding O
in O
different O
populations O
and O
ethnic O
groups O
. O
This O
is O
particularly O
evident O
in O
countries O
and O
ethnic O
populations O
of O
the B-LOC
Arabian I-LOC
Peninsula I-LOC
. O
Human O
MHC O
haplotypes O
, O
and O
its O
association O
with O
diseases O
, O
of O
the O
variable O
ethnic O
groups O
of O
this O
region O
are O
poorly O
studied O
. O
This O
review O
compiled O
published O
manuscripts O
that O
have O
reported O
a O
list O
of O
autoimmune O
diseases O
( O
insulin O
- O
dependent O
diabetes O
mellitus O
, O
systemic O
lupus O
erythematosus O
, O
myasthenia O
gravis O
, O
rheumatoid O
arthritis O
, O
psoriasis O
vulgaris O
, O
and O
multiple O
sclerosis O
) O
associated O
with O
MHC O
class O
I O
and O
class O
II O
in O
the O
populations O
of O
the B-LOC
Arabian I-LOC
Peninsula I-LOC
, O
specifically O
Bahrain B-LOC
, O
Kuwait B-LOC
, O
Oman B-LOC
, O
Qatar B-LOC
, O
Saudi B-LOC
Arabia I-LOC
, O
the B-LOC
United I-LOC
Arab I-LOC
Emirates I-LOC
, O
and O
Yemen B-LOC
. O
Data O
available O
was O
compared O
with O
other O
three O
ethnic O
groups O
, O
namely O
Caucasians O
, O
Asians O
, O
and O
Africans O
. O
The O
limited O
data O
available O
in O
the O
public O
domain O
on O
the O
association O
between O
MHC O
gene O
and O
autoimmune O
diseases O
highlight O
the O
challenges O
in O
the O
Middle B-LOC
Eastern I-LOC
region O
. O
Charcot O
- O
Marie O
- O
Tooth O
disease O
( O
CMT O
) O
is O
a O
common O
inherited O
peripheral O
neuropathy O
affecting O
up O
to O
1 B-STAT
in I-STAT
1214 I-STAT
of O
the O
general O
population O
with O
more O
than O
60 O
nuclear O
genes O
implicated O
in O
its O
pathogenesis O
. O
Traditional O
molecular O
diagnostic O
pathways O
based O
on O
relative O
prevalence B-EPI
and O
clinical O
phenotyping O
are O
limited O
by O
long O
turnaround O
time O
, O
population O
- O
specific O
prevalence B-EPI
of O
causative O
variants O
and O
inability O
to O
assess O
multiple O
co O
- O
existing O
variants O
. O
In O
this O
study O
, O
a O
CMT O
gene O
panel O
comprising O
27 O
genes O
was O
used O
to O
uncover O
the O
pathogenic O
mutations O
in O
two O
index O
patients O
. O
The O
first O
patient O
is O
a O
15 O
- O
year O
- O
old O
boy O
, O
born O
of O
consanguineous O
parents O
, O
who O
has O
had O
frequent O
trips O
and O
falls O
since O
infancy O
, O
and O
was O
later O
found O
to O
have O
inverted O
champagne O
bottle O
appearance O
of O
bilateral O
legs O
and O
foot O
drop O
. O
His O
elder O
sister O
is O
similarly O
affected O
. O
The O
second O
patient O
is O
a O
37 O
- O
year O
- O
old O
woman O
referred O
for O
pre O
- O
pregnancy O
genetic O
diagnosis O
. O
During O
early O
adulthood O
, O
she O
developed O
progressive O
lower O
limb O
weakness O
, O
difficulties O
in O
tip O
- O
toe O
walking O
and O
thinning O
of O
calf O
muscles O
. O
Both O
patients O
are O
clinically O
compatible O
with O
CMT O
, O
have O
undergone O
multiple O
genetic O
testings O
and O
have O
not O
previously O
received O
a O
definitive O
genetic O
diagnosis O
. O
Patients O
1 B-STAT
and I-STAT
2 I-STAT
were O
found O
to O
have O
pathogenic O
homozygous O
HSPB1 O
: O
NM_001540 O
: O
c.250G O
> O
A O
( O
p. O
G84R O
) O
variant O
and O
heterozygous O
GDAP1 O
: O
NM_018972 O
: O
c.358C O
> O
T O
( O
p. O
R120W O
) O
variant O
, O
respectively O
. O
Advantages O
and O
limitations O
of O
the O
current O
approach O
are O
discussed O
. O
Mutations O
in O
the O
COL4A5 O
gene O
, O
located O
at O
Xq22 O
, O
cause O
Alport O
syndrome O
( O
AS O
) O
, O
a O
nephritis O
characterized O
by O
progressive O
deterioration O
of O
the O
glomerular O
basement O
membrane O
and O
usually O
associated O
with O
progressive O
hearing O
loss O
. O
We O
have O
identified O
a O
novel O
mutation O
, O
L1649R O
, O
present O
in O
9 O
of O
121 O
independently O
ascertained O
families O
. O
Affected O
males O
shared O
the O
same O
haplotype O
of O
eight O
polymorphic O
markers O
tightly O
linked O
to O
COL4A5 O
, O
indicating O
common O
ancestry O
. O
Genealogical O
studies O
place O
the O
birth O
of O
this O
ancestor O
> O
200 O
years O
ago O
. O
The O
L1649R O
mutation O
is O
a O
relatively O
common O
cause O
of O
Alport B-LOC
syndrome O
in O
the O
western O
United B-LOC
States I-LOC
, O
in O
part O
because O
of O
the O
rapid O
growth O
and O
migratory O
expansion O
of O
mid O
- O
nineteenth O
- O
century O
pioneer O
populations O
carrying O
the O
gene O
. O
L1649R O
affects O
a O
highly O
conserved O
residue O
in O
the O
NC1 O
domain O
, O
which O
is O
involved O
in O
key O
inter- O
and O
intramolecular O
interactions O
, O
but O
results O
in O
a O
relatively O
mild O
disease O
phenotype O
. O
Renal O
failure O
in O
an O
L1649R O
male O
typically O
occurs B-EPI
in O
the O
4th O
or O
5th O
decade O
and O
precedes O
the O
onset O
of O
significant O
hearing O
loss O
by O
approximately O
10 O
years O
. O
Background O
To O
evaluate O
clinical O
, O
genetic O
, O
and O
radiologic O
features O
of O
our O
patients O
with O
muscle O
- O
eye O
- O
brain O
disease O
. O
Methods O
The O
data O
of O
patients O
who O
were O
diagnosed O
with O
muscle O
- O
eye O
- O
brain O
disease O
from O
a O
cohort O
of O
patients O
with O
congenital O
muscular O
dystrophy O
in O
the O
Division O
of O
Pediatric O
Neurology O
of O
Dokuz O
Eylül O
University O
School O
of O
Medicine O
and O
Gaziantep O
Children O
's O
Hospital O
between O
2005 O
and O
2013 O
were O
analyzed O
retrospectively O
. O
Results O
From O
a O
cohort O
of O
34 O
patients O
with O
congenital O
muscular O
dystrophy O
, O
12 O
patients O
from O
10 O
families O
were O
diagnosed O
with O
muscle O
- O
eye O
- O
brain O
disease O
. O
The O
mean O
age O
of O
the O
patients O
was O
9 O
± O
5.5 O
years O
( O
2 O
- O
19 O
years O
) O
. O
Mean O
serum O
creatine O
kinase O
value O
was O
2485.80 O
± O
1308.54 O
IU O
/ O
L O
( O
700 O
- O
4267 O
IU O
/ O
L O
) O
. O
All O
patients O
presented O
with O
muscular O
hypotonia O
at O
birth O
followed O
by O
varying O
degrees O
of O
spasticity O
and O
exaggerated O
deep O
tendon O
reflexes O
in O
later O
stages O
of O
life O
. O
Three O
patients O
were O
able O
to O
walk O
. O
The O
most O
common O
ophthalmologic O
and O
radiologic O
abnormalities O
were O
cataracts O
, O
retinal O
detachment O
, O
periventricular O
white O
matter O
abnormalities O
, O
ventriculomegaly O
, O
pontocerebellar O
hypoplasia O
, O
and O
multiple O
cerebellar O
cysts O
. O
All O
of O
the O
patients O
had O
mutations O
in O
the O
POMGNT1 O
gene O
. O
The O
most O
common O
mutation O
detected O
in O
66 O
% O
of O
patients O
was O
c.1814 O
G O
> O
A O
( O
p. O
R605H O
) O
. O
Two O
novel O
mutations O
were O
identified O
. O
Conclusions O
We O
suggest O
that O
muscle O
- O
eye O
- O
brain O
disease O
is O
a O
relatively O
common O
muscular O
dystrophy O
in O
Turkey B-LOC
. O
It O
should O
be O
suspected O
in O
patients O
with O
muscular O
hypotonia O
, O
increased O
creatine O
kinase O
, O
and O
structural O
eye O
and O
brain O
abnormalities O
. O
The O
c.1814 O
G O
> O
A O
mutation O
in O
exon O
21 O
of O
the O
POMGNT1 O
gene O
is O
apparently O
a O
common O
mutation O
in O
the O
Turkish O
population O
. O
Individuals O
with O
this O
mutation O
show O
classical O
features O
of O
muscle O
- O
eye O
- O
brain O
disease O
, O
but O
others O
may O
exhibit O
a O
milder O
phenotype O
and O
retain O
the O
ability O
to O
walk O
independently O
. O
Congenital O
muscular O
dystrophy O
patients O
from O
Turkey B-LOC
carrying O
the O
clinical O
and O
radiologic O
features O
of O
muscle O
- O
eye O
- O
brain O
disease O
should O
be O
evaluated O
for O
mutations O
in O
POMGNT1 O
gene O
. O
Since O
its O
first O
clinical O
description O
( O
on O
his O
son O
) O
by O
William O
James O
West O
( O
1793 O
- O
1848 O
) O
in O
1841 O
, O
and O
the O
definition O
of O
the O
classical O
triad O
of O
( O
1 O
) O
infantile O
spasms O
; O
( O
2 O
) O
hypsarrhythmia O
, O
and O
( O
3 O
) O
developmental O
arrest O
or O
regression O
as O
O
West O
syndrome O
O
, O
new O
and O
relevant O
advances O
have O
been O
recorded O
in O
this O
uncommon O
disorder O
. O
New O
approaches O
include O
terminology O
of O
clinical O
spasms O
( O
e.g. O
, O
infantile O
( O
IS O
) O
vs. O
epileptic O
spasms O
( O
ES O
) O
) O
, O
variety O
of O
clinical O
and O
electroencephalographic O
( O
EEG O
) O
features O
( O
e.g. O
, O
typical O
ictal O
phenomena O
without O
EEG O
abnormalities O
) O
, O
burden O
of O
developmental O
delay O
, O
spectrum O
of O
associated O
genetic O
abnormalities O
, O
pathogenesis O
, O
treatment O
options O
, O
and O
related O
outcome O
and O
prognosis O
. O
Aside O
the O
classical O
manifestations O
, O
IS O
or O
ES O
may O
present O
with O
atypical O
electroclinical O
phenotypes O
( O
e.g. O
, O
subtle O
spasms O
; O
modified O
hypsarrhythmia O
) O
and O
may O
have O
their O
onset O
outside O
infancy O
. O
An O
increasing O
number O
of O
genes O
, O
proteins O
, O
and O
signaling O
pathways O
play O
crucial O
roles O
in O
the O
pathogenesis O
. O
This O
condition O
is O
currently O
regarded O
as O
a O
spectrum O
of O
disorders O
: O
the O
so O
- O
called O
infantile O
spasm O
syndrome O
( O
ISs O
) O
, O
in O
association O
with O
other O
causal O
factors O
, O
including O
structural O
, O
infectious O
, O
metabolic O
, O
syndromic O
, O
and O
immunologic O
events O
, O
all O
acting O
on O
a O
genetic O
predisposing O
background O
. O
Hormonal O
therapy O
and O
ketogenic O
diet O
are O
widely O
used O
also O
in O
combination O
with O
( O
classical O
and O
recent O
) O
pharmacological O
drugs O
. O
Biologically O
targeted O
and O
gene O
therapies O
are O
increasingly O
studied O
. O
The O
present O
narrative O
review O
searched O
in O
seven O
electronic O
databases O
( O
primary O
MeSH O
terms O
/ O
keywords O
included O
West O
syndrome O
, O
infantile O
spasms O
and O
infantile O
spasms O
syndrome O
and O
were O
coupled O
to O
25 O
secondary O
clinical O
, O
EEG O
, O
therapeutic O
, O
outcomes O
, O
and O
associated O
conditions O
terms O
) O
including O
MEDLINE O
, O
Embase O
, O
Cochrane O
Central O
, O
Web O
of O
Sciences O
, O
Pubmed O
, O
Scopus O
, O
and O
OMIM O
to O
highlight O
the O
past O
knowledge O
and O
more O
recent O
advances O
. O
The O
urea O
cycle O
is O
a O
series O
of O
metabolic O
reactions O
that O
convert O
ammonia O
into O
urea O
in O
order O
to O
eliminate O
it O
from O
the O
body O
. O
Urea O
cycle O
disorders O
are O
characterized O
by O
hyperammonemia O
, O
which O
can O
cause O
irreversible O
damages O
in O
central O
nervous O
system O
. O
We O
report O
a O
series O
of O
three O
newborns O
presenting O
irritability O
, O
poor O
feeding O
and O
tachypnea O
. O
Their O
first O
gas O
analysis O
revealed O
respiratory O
alkalosis O
. O
Hyperammonemia O
was O
confirmed O
, O
and O
three O
different O
enzymatic O
blocks O
in O
the O
urea O
cycle O
were O
diagnosed O
. O
Immediate O
treatment O
consisted O
in O
the O
removal O
of O
ammonia O
by O
reduction O
of O
the O
catabolic O
state O
, O
dietary O
adjustments O
, O
use O
of O
nitrogen O
scavenging O
agents O
and O
ultimately O
hemodiafiltration O
. O
Hyperammonemia O
is O
a O
medical O
emergency O
whose O
treatment O
should O
not O
be O
delayed O
. O
This O
report O
aims O
to O
highlight O
the O
importance O
of O
suspecting O
urea O
cycle O
disorders O
in O
newborns O
with O
aspecific O
signs O
of O
hyperammonemia O
and O
respiratory O
alkalosis O
, O
and O
to O
sum O
up O
the O
broad O
lines O
of O
hyperammonemia O
management O
. O
Purpose O
The O
eye O
and O
its O
adnexal O
structures O
can O
give O
rise O
to O
first O
or O
consecutive O
primary O
malignancies O
or O
to O
encounter O
metastasis O
. O
Our O
aim O
was O
to O
define O
the O
characteristics O
of O
the O
second O
primary O
neoplasms O
affecting O
the O
eye O
and O
its O
adnexa O
and O
find O
the O
risk O
modifying O
factors O
for O
them O
after O
malignancies O
elsewhere O
in O
the O
body O
. O
Methods O
We O
have O
queried O
the O
Surveillance O
, O
Epidemiology O
and O
End O
- O
Results O
O
SEER-9 O
program O
of O
the O
National O
Cancer O
Institute O
for O
the O
malignancies O
of O
the O
eye O
and O
its O
adnexa O
that O
occurred O
between O
1973 O
and O
2015 O
. O
The O
malignancies O
were O
ordered O
chronologically O
according O
to O
their O
incidence B-EPI
: O
first O
or O
second O
primary O
malignancies O
. O
The O
tumors O
were O
classified O
according O
to O
ICD O
- O
O-3 O
classification O
. O
Standardized O
incidence B-EPI
ratios O
( O
SIR O
) O
and O
survival O
probabilities O
were O
calculated O
for O
subgroups O
. O
Results O
Among O
3,578,950 O
cancer O
patients O
, O
1203 O
experienced O
a O
second O
malignancies O
of O
the O
eye O
and O
its O
adnexa O
. O
The O
first O
malignancy O
was O
diagnosed O
between O
50 O
and O
69 O
years O
of O
age O
in O
58.94 O
% O
of O
them O
. O
The O
eyelid O
showed O
280 O
events O
, O
while O
50 O
in O
lacrimal O
gland O
, O
181 O
in O
the O
orbit O
, O
21 O
in O
the O
overlapping O
lesions O
, O
15 O
in O
optic O
nerve O
, O
148 O
in O
the O
conjunctiva O
, O
9 O
in O
the O
cornea O
, O
6 O
in O
the O
Retina O
, O
379 O
in O
the O
choroid O
, O
and O
93 O
in O
the O
ciliary O
body O
. O
The O
SIR O
of O
a O
second O
malignancy O
after O
a O
prior O
non O
- O
Hodgkin O
lymphoma O
was O
2.42 O
, O
and O
in O
case O
of O
previous O
skin O
carcinomas O
it O
was O
3.02 O
, O
melanoma O
of O
skin O
, O
and O
2.13 O
and O
1.58 O
in O
oral O
cavity O
/ O
pharynx O
malignancies O
. O
The O
second O
ocular O
and O
adnexal O
neoplasms O
increased O
steadily O
over O
the O
5 O
- O
year O
periods O
on O
contrary O
to O
first O
primary O
neoplasms O
. O
The O
survival O
of O
patients O
affected O
with O
first O
ocular O
and O
adnexal O
neoplasms O
was O
significantly O
higher O
than O
those O
with O
second O
ocular O
and O
adnexal O
neoplasms O
. O
On O
the O
other O
side O
, O
second O
primary O
ocular O
and O
adnexal O
tumors O
showed O
a O
better O
survival O
than O
second O
primary O
malignancies O
elsewhere O
. O
Conclusions O
The O
epidemiological O
differences O
between O
first O
and O
second O
ocular O
and O
adnexal O
primaries O
suggest O
different O
underlying O
mechanisms O
. O
Careful O
ocular O
examination O
should O
be O
integrated O
in O
the O
long O
- O
term O
follow O
- O
up O
plan O
of O
cancer O
patients O
. O
Special O
attention O
should O
be O
given O
to O
patients O
with O
non O
- O
Hodgkin O
's O
lymphoma O
and O
melanoma O
as O
first O
primary O
. O
Background O
Primary O
immune O
deficiencies O
( O
PIDs O
) O
are O
a O
heterogeneous O
group O
of O
disorders O
resulting O
from O
defects O
in O
immune O
system O
. O
They O
lead O
to O
increased O
susceptibility O
to O
infections O
and O
immune O
dysregulation O
. O
The O
resulting O
chronic O
inflammation O
can O
induce O
long O
- O
term O
complications O
, O
including O
AA O
amyloidosis O
( O
AAA O
) O
. O
Objectives O
To O
present O
the O
French O
cases O
of O
PID O
- O
related O
AAA O
and O
perform O
a O
systematic O
literature O
review O
to O
determine O
its O
main O
features O
and O
predisposing O
factors O
. O
Methods O
A O
systematic O
literature O
review O
was O
performed O
by O
searching O
MEDLINE O
up O
until O
2019 O
. O
New O
French O
cases O
were O
identified O
with O
the O
help O
of O
the O
Reference O
Center O
for O
Auto O
- O
Inflammatory O
Diseases O
and O
AA O
Amyloidosis O
and O
the O
Reference O
Center O
for O
Hereditary O
Immune O
Deficiencies O
. O
Results O
Forty O
patients O
were O
identified O
including O
2 O
new O
French O
cases O
. O
PIDs O
were O
varied O
: O
immunoglobulin O
deficits O
( O
n O
= O
30 O
) O
, O
chronic O
granulomatous O
disease O
( O
n O
= O
3 O
) O
, O
hyper O
- O
IgM O
syndrome O
( O
n O
= O
3 O
) O
, O
hereditary O
complete O
C4 O
deficiency O
( O
n O
= O
1 O
) O
, O
leucocyte O
adhesion O
deficiency O
type O
1 O
( O
n O
= O
1 O
) O
, O
hyper O
- O
IgE O
syndrome O
( O
n O
= O
1 O
) O
, O
and O
Chediak O
- O
Higashi O
syndrome O
( O
n O
= O
1 O
) O
. O
The O
mean O
age O
at O
PID O
diagnosis O
was O
22.2 O
± O
16.02 O
years O
. O
Renal O
involvement O
was O
the O
most O
common O
manifestation O
of O
AAA O
( O
80 O
% O
) O
. O
Infections O
were O
extremely O
heterogeneous O
; O
bacterial O
infection O
with O
pulmonary O
involvement O
was O
the O
most O
frequent O
. O
Bronchiectasis O
was O
particularly O
common O
( O
52.5 O
% O
) O
. O
The O
delay O
between O
the O
first O
symptoms O
of O
PID O
and O
AAA O
diagnosis O
was O
16.18 O
± O
7 O
years O
. O
Thirteen O
concomitant O
diagnoses O
were O
made O
. O
Twenty O
patients O
died O
during O
follow O
- O
up O
. O
Conclusion O
AAA O
is O
a O
rare O
life O
- O
threatening O
complication O
of O
PID O
, O
especially O
in O
cases O
of O
long O
diagnostic O
and O
therapeutic O
delays O
. O
Bronchiectasis O
should O
be O
considered O
as O
a O
warning O
sign O
of O
chronic O
inflammation O
and O
increased O
risk O
of O
AAA O
. O
Objectives O
Generally O
, O
neuropathies O
of O
peripheral O
nerves O
are O
a O
frequent O
condition O
( O
prevalence B-EPI
2 B-STAT
- O
3 O
% O
) O
and O
most O
frequently O
due O
to O
alcoholism O
, O
diabetes O
, O
renal O
insufficiency O
, O
malignancy O
, O
toxins O
, O
or O
drugs O
. O
However O
, O
the O
vast O
majority O
of O
neuropathies O
has O
orphan O
status O
. O
This O
review O
focuses O
on O
the O
etiology O
, O
frequency O
, O
diagnosis O
, O
and O
treatment O
of O
orphan O
neuropathies O
. O
Methods O
Literature O
reviewResults O
: O
Rareness O
of O
diseases O
is O
not O
uniformly O
defined O
but O
in O
the O
US B-LOC
an O
orphan O
disease O
is O
diagnosed O
if O
the O
prevalence B-EPI
is O
< B-STAT
1:200000 I-STAT
, O
in O
Europe B-LOC
if O
< O
5:10000 O
. O
Most O
acquired O
and O
hereditary O
neuropathies O
are O
orphan O
diseases O
. O
Often O
the O
causative O
variant O
has O
been O
reported O
only O
in O
a O
single O
patient O
or O
family O
, O
particularly O
the O
ones O
that O
are O
newly O
detected O
( O
e.g. O
SEPT9 O
, O
SORD O
) O
. O
Among O
the O
complex O
neuropathies O
( O
hereditary O
multisystem O
disorders O
with O
concomitant O
neuropathies O
) O
orphan O
forms O
have O
been O
reported O
among O
mitochondrial O
disorders O
( O
e.g. O
NARP O
, O
MNGIE O
, O
SANDO O
) O
, O
spinocerebellar O
ataxias O
( O
e.g. O
TMEM240 B-LOC
) O
, O
hereditary O
spastic O
paraplegias O
( O
e.g O
UBAP1 O
) O
, O
lysosomal O
storage O
disease O
( O
e.g. O
Schindler O
disease O
) O
, O
peroxisomal O
disorders O
, O
porphyrias O
, O
and O
other O
types O
( O
e.g. O
giant O
axonal O
neuropathy O
, O
Tangier O
disease O
) O
. O
Orphan O
acquired O
neuropathies O
include O
the O
metabolic O
neuropathies O
( O
e.g. O
vitamin O
- O
B1 O
, O
folic O
acid O
) O
, O
toxic O
neuropathies O
( O
e.g. O
copper O
, O
lithium O
, O
lead O
, O
arsenic O
, O
thallium O
, O
mercury O
) O
, O
infectious O
neuropathies O
, O
immune O
- O
mediated O
( O
e.g. O
Bruns O
- O
Garland O
syndrome O
) O
, O
and O
neoplastic O
/ O
paraneoplastic O
neuropathies O
. O
Conclusions O
Though O
orphan O
neuropathies O
are O
rare O
per O
definition O
they O
constitute O
the O
majority O
of O
neuropathies O
and O
should O
be O
considered O
as O
some O
of O
them O
are O
easy O
to O
identify O
and O
potentially O
treatable O
, O
as O
clarification O
of O
the O
underlying O
cause O
may O
contribute O
to O
the O
knowledge O
about O
etiology O
and O
pathophysiology O
of O
these O
conditions O
, O
and O
as O
the O
true O
prevalence B-EPI
may O
become O
obvious O
only O
if O
all O
ever O
diagnosed O
cases O
are O
reported O
. O
On O
3 O
August O
1900 O
, O
bubonic O
plague O
( O
Yersinia O
pestis O
) O
broke O
out O
in O
Glasgow B-LOC
for O
the O
first O
time O
during O
the O
Third O
Pandemic O
. O
The O
local O
sanitary O
authorities O
rigorously O
tracked O
the O
spread O
of O
the O
disease O
and O
they O
found O
that O
nearly O
all O
of O
the O
35 O
cases O
could O
be O
linked O
by O
contact O
with O
a O
previous O
case O
. O
Despite O
trapping O
hundreds O
of O
rats O
in O
the O
area O
, O
there O
was O
no O
evidence O
of O
a O
rat O
epizootic O
and O
the O
investigators O
speculated O
that O
the O
outbreak O
could O
be O
due O
to O
human O
- O
to O
- O
human O
transmission O
of O
bubonic O
plague O
. O
Here O
we O
use O
a O
likelihood O
- O
based O
method O
to O
reconstruct O
transmission O
trees O
for O
the O
outbreak O
. O
From O
the O
description O
of O
the O
outbreak O
and O
the O
reconstructed O
trees O
, O
we O
infer O
several O
epidemiological O
parameters O
. O
We O
found O
that O
the O
estimated O
mean O
serial O
interval O
was O
7.4 O
- O
9.2 O
days O
and O
the O
mean O
effective O
reproduction O
number O
dropped O
below O
1 O
after O
implementation O
of O
control O
measures O
. O
We O
also O
found O
a O
high O
rate O
of O
secondary O
transmissions O
within O
households O
and O
observations O
of O
transmissions O
from O
individuals O
who O
were O
not O
terminally O
septicaemic O
. O
Our O
results O
provide O
important O
insights O
into O
the O
epidemiology O
of O
a O
bubonic O
plague O
outbreak O
during O
the O
Third O
Pandemic O
in O
Europe B-LOC
. O
Aim O
To O
assess O
the O
prevalence B-EPI
of O
persistent O
lipid O
abnormalities O
in O
statin O
- O
treated O
patients O
with O
diabetes O
with O
and O
without O
the O
metabolic O
syndrome O
. O
Methods O
This O
was O
a O
cross O
- O
sectional O
study O
of O
22,063 O
statin O
- O
treated O
outpatients O
consecutively O
recruited O
by O
clinicians O
in O
Canada B-LOC
and O
11 O
European O
countries O
. O
Patient O
cardiovascular O
risk O
factors O
, O
risk O
level O
, O
lipid O
measurements O
and O
lipid O
- O
modifying O
medication O
regimens O
were O
recorded O
. O
Results O
Of O
the O
20,129 O
subjects O
who O
had O
documented O
diabetes O
and/or O
metabolic O
syndrome O
status O
, O
41 O
% O
had O
diabetes O
( O
of O
whom O
86.8 O
% O
also O
had O
the O
metabolic O
syndrome O
) O
. O
Of O
those O
with O
diabetes O
, O
48.1 O
% O
were O
not O
at O
total O
cholesterol O
target O
compared O
with O
58 O
% O
of O
those O
without O
diabetes O
. O
Amongst O
those O
with O
diabetes O
, O
41.6 O
and O
41.3 O
% O
of O
those O
with O
and O
without O
the O
metabolic O
syndrome O
, O
respectively O
, O
were O
not O
at O
their O
LDL O
cholesterol O
goal O
relative B-STAT
to O
54.2 O
% O
of O
those O
with O
metabolic O
syndrome O
and O
without O
diabetes O
, O
and O
52 O
% O
of O
those O
with O
neither O
condition O
. O
Twenty B-STAT
per I-STAT
cent I-STAT
of I-STAT
people O
with O
diabetes O
but O
without O
the O
metabolic O
syndrome O
were O
not O
at O
the O
optimal O
HDL O
cholesterol O
level O
compared O
with O
9 O
% O
of O
those O
with O
neither O
condition O
. O
Of O
people O
with O
diabetes O
and O
the O
metabolic O
syndrome O
, O
49.9 O
% O
were O
not O
at O
optimal O
triglyceride O
level O
relative B-STAT
to O
13.5 O
% O
of O
people O
with O
neither O
diabetes O
nor O
the O
metabolic O
syndrome O
. O
Simvastatin O
was O
the O
most O
commonly O
prescribed O
statin O
( O
> O
45 O
% O
) O
and O
the O
most O
common O
statin O
potency O
was O
20 O
- O
40 O
mg O
/ O
day O
( O
simvastatin O
equivalent O
) O
. O
Approximately O
14 O
% O
of O
patients O
were O
taking O
ezetimibe O
alone O
or O
in O
combination O
with O
a O
statin O
. O
Conclusions O
Despite O
evidence O
supporting O
the O
benefits O
of O
lipid O
modification O
and O
international O
guideline O
recommendations O
, O
statin O
- O
treated O
patients O
with O
diabetes O
had O
a O
high O
prevalence B-EPI
of O
persistent O
lipid O
abnormalities O
. O
There O
is O
frequently O
room O
to O
optimize O
therapy O
through O
statin O
dose O
up O
- O
titration O
and/or O
addition O
of O
other O
lipid O
- O
modifying O
therapies O
. O
Osteogenesis O
imperfecta O
describes O
a O
group O
of O
genetic O
disorders O
that O
result O
from O
a O
defect O
in O
collagen O
type O
I O
and O
range O
in O
severity O
from O
a O
subtle O
increase O
in O
fracture O
frequency O
to O
death O
in O
the O
perinatal O
period O
. O
Osteogenesis O
imperfecta O
is O
mostly O
caused O
by O
mutations O
in O
the O
COL1A1 O
( O
17q21.33 O
) O
and O
COL1A2 O
( O
7q21.3 O
) O
genes O
. O
There O
have O
only O
been O
a O
few O
case O
reports O
of O
implant O
- O
prosthetic O
treatment O
for O
patients O
with O
osteogenesis O
imperfecta O
. O
These O
reports O
indicated O
that O
implants O
and O
augmentation O
procedures O
can O
be O
implemented O
in O
such O
patients O
. O
However O
, O
for O
patients O
receiving O
additional O
antiresorptive O
therapy O
, O
cautious O
approaches O
should O
be O
chosen O
and O
the O
risk O
of O
drug O
- O
associated O
osteonecrosis O
should O
be O
considered O
. O
The O
aim O
of O
this O
article O
is O
to O
report O
on O
the O
implant O
- O
prosthetic O
treatment O
of O
a O
patient O
with O
type O
I O
osteogenesis O
imperfecta O
. O
Microcephalic O
osteodysplastic O
primordial O
dwarfism O
type O
II O
( O
OMIM O
210720 O
) O
is O
a O
rare O
autosomal O
recessive O
condition O
frequently O
associated O
with O
early O
- O
onset O
cerebrovascular O
disease O
. O
Presymptomatic O
detection O
and O
intervention O
could O
prevent O
the O
adverse O
consequences O
associated O
with O
this O
. O
We O
reviewed O
published O
cases O
of O
microcephalic O
osteodysplastic O
primordial O
dwarfism O
type O
II O
to O
ascertain O
prevalence B-EPI
and O
characteristics O
of O
cerebrovascular O
disease O
and O
use O
these O
data O
to O
propose O
an O
evidence O
- O
based O
approach O
to O
cerebrovascular O
screening O
. O
Of O
147 O
cases O
identified O
, O
47 O
had O
cerebrovascular O
disease O
( O
32 O
% O
) O
, O
including O
occlusive O
arteriopathy O
( O
including O
moyamoya O
) O
and O
cerebral O
aneurysmal O
disease O
. O
Occlusive O
disease O
occurred O
in O
younger O
individuals O
, O
and O
progression O
can O
be O
both O
rapid O
and O
clinically O
silent O
. O
A O
reasonable O
screening O
approach O
would O
be O
magnetic O
resonance O
imaging O
and O
angiography O
of O
the O
cervical O
and O
intracranial O
circulation O
at O
diagnosis O
, O
repeated O
at O
yearly O
intervals O
until O
10 O
years O
, O
and O
every O
2 O
years O
thereafter O
, O
unless O
clinical O
concerns O
occur O
earlier O
. O
At O
present O
it O
would O
appear O
that O
this O
needs O
to O
be O
life O
- O
long O
. O
Families O
and O
professionals O
should O
be O
alerted O
to O
the O
potential O
significance O
of O
neurologic O
symptoms O
and O
measures O
should O
be O
taken O
to O
maintain O
good O
vascular O
health O
in O
affected O
individuals O
. O
Background O
Retroviruses O
of O
human O
T O
- O
lymphotropic O
viruses O
( O
HTLV-1 O
and O
HTLV-2 O
) O
have O
been O
demonstrated O
to O
be O
endemic O
in O
the O
north O
- O
eastern O
region O
of O
Iran B-LOC
. O
This O
study O
was O
aimed O
to O
determine O
the O
HTLV-1 O
and O
HTLV-2 O
prevalence B-EPI
among O
healthy O
individuals O
in O
Neyshabur B-LOC
City I-LOC
during O
2010 O
- O
2014 O
. O
Methods O
A O
total O
of O
8054 O
blood O
samples O
were O
collected O
from O
healthy O
participants O
in O
Neyshabur B-LOC
, O
North B-LOC
- I-LOC
Eastern I-LOC
Iran B-LOC
. O
The O
blood O
samples O
were O
screened O
for O
the O
presence O
of O
specific O
antibodies O
against O
HTLV-1 O
and O
HTLV-2 O
by O
using O
ELISA O
according O
to O
the O
manufacturer O
's O
instructions O
. O
Results O
The O
overall O
seropositivity O
rate O
for O
HTLV-1 O
and O
HTLV-2 O
was O
found O
to O
be O
6.55 O
% O
( O
528 O
out O
of O
8054 O
) O
among O
participants O
. O
Conclusion O
Both O
HTLV-1 O
and O
HTLV-2 O
were O
demonstrated O
to O
be O
at O
a O
high O
rate O
in O
healthy O
individuals O
. O
However O
, O
a O
smaller O
number O
of O
asymptomatic O
carriers O
were O
found O
in O
this O
study O
, O
as O
compared O
to O
those O
identified O
in O
previous O
investigations O
in O
the O
city O
. O
The O
periampullary O
neuroendocrine O
tumour O
is O
an O
infrequently O
occurring O
tumour O
. O
Its O
prevalence B-EPI
among O
gastrointestinal O
neuroendocrine O
neoplasms O
is O
less B-STAT
than I-STAT
0.3 I-STAT
% I-STAT
, O
and O
less B-STAT
than O
2 O
% O
out O
of O
periampullary O
tumours O
. O
These O
neoplasms O
have O
relatively O
poor O
prognosis O
. O
Jaundice O
and O
pain O
in O
the O
abdomen O
are O
the O
early O
and O
most O
commonly O
occurring O
symptoms O
with O
weight O
loss O
being O
a O
late O
event O
. O
The O
carcinoid O
syndrome O
presents O
infrequently O
in O
periampullary O
neuroendocrine O
tumour O
and O
happens O
only O
if O
hepatic O
metastasis O
occurs B-EPI
. O
In O
this O
scenario O
, O
histopathology O
plays O
a O
paramount O
role O
in O
the O
diagnosis O
. O
Specific O
immunohistochemical O
staining O
is O
used O
for O
diagnosis O
while O
the O
treatment O
options O
are O
local O
excision O
, O
endoscopic O
excision O
and O
pancreaticoduodenectomy O
. O
Here O
is O
a O
case O
report O
of O
a O
42 O
- O
year O
- O
old O
patient O
who O
presented O
with O
complaint O
of O
obstructive O
jaundice O
for O
one O
month O
. O
Periampullary O
carcinoid O
tumour O
was O
diagnosed O
on O
biopsy O
, O
and O
she O
underwent O
Pancreaticoduodenectomy O
as O
treatment O
. O
Literature O
shows O
that O
there O
is O
poor O
precision O
of O
preoperative O
and O
intraoperative O
lymph O
node O
metastatic O
involvement O
regardless O
of O
the O
size O
of O
the O
tumour O
. O
Hence O
, O
radical O
resection O
must O
be O
considered O
the O
standard O
approach O
. O
Mayer O
Rokitansky O
Kuster O
Hauser O
( O
MRKH O
) O
syndrome O
is O
a O
congenital O
disorder O
involving O
reproductive O
, O
genitourinary O
, O
bone O
, O
and O
cardiac O
malformation O
. O
The O
incidence B-EPI
is O
1 B-STAT
in I-STAT
4000 I-STAT
- O
5000 O
females O
livebirths O
. O
The O
phenotype O
is O
female O
46 O
XX O
karyotype O
, O
normal O
secondary O
sexual O
characteristics O
, O
and O
normal O
functional O
ovaries O
. O
The O
occurrence B-EPI
of O
leiomyoma O
in O
uterine O
remnant O
in O
MRKH O
syndrome O
is O
a O
very O
rare O
case O
, O
even O
though O
several O
cases O
have O
been O
reported O
. O
The O
diagnosis O
and O
management O
approach O
, O
in O
this O
case O
, O
is O
quite O
challenging O
. O
Here O
, O
we O
report O
a O
38 O
years O
old O
female O
who O
represents O
multiple O
leiomyomas O
on O
the O
rudimentary O
uterus O
, O
then O
we O
did O
laparoscopic O
removal O
of O
the O
fibroids O
and O
adjacent O
rudimentary O
uterus O
. O
Transient O
global O
amnesia O
( O
TGA O
) O
is O
a O
neurological O
syndrome O
with O
rather O
distinctive O
brain O
MRI O
features O
, O
namely O
hyperintense O
lesion O
in O
hippocampus O
on O
diffusion O
- O
weighted O
imaging O
( O
DWI O
) O
and O
fluid O
- O
attenuated O
inversion O
recovery O
( O
FLAIR O
) O
sequences O
. O
Post O
- O
traumatic O
amnesia O
is O
another O
amnestic O
syndrome O
which O
can O
also O
show O
hyperintense O
lesions O
in O
brain O
MRI O
due O
to O
cytotoxic O
oedema O
caused O
by O
traumatic O
brain O
injury O
. O
We O
present O
a O
case O
of O
a O
patient O
with O
post O
- O
traumatic O
amnesia O
with O
a O
brain O
MRI O
image O
mimic O
of O
TGA O
. O
Objectives O
West B-LOC
Nile I-LOC
virus O
( O
WNV O
) O
is O
a O
re O
- O
emerging O
mosquito O
- O
borne O
viral O
infection O
. O
This O
study O
investigated O
the O
pooled B-EPI
prevalence I-EPI
pattern O
and O
risk O
factors O
of O
WNV O
infection O
among O
humans O
and O
animals O
in O
Nigeria B-LOC
. O
Methods O
A O
systematic O
review O
was O
conducted O
of O
eligible O
studies O
published O
in O
PubMed O
, O
Scopus O
, O
Google O
Scholar O
, O
and O
Web O
of O
Science O
from O
January O
1 O
, O
1950 O
to O
August O
30 O
, O
2020 O
. O
Peer O
- O
reviewed O
cross O
- O
sectional O
studies O
describing O
WNV O
infections O
in O
humans O
and O
animals O
were O
systematically O
reviewed O
. O
Heterogeneity O
was O
assessed O
using O
the O
Cochrane O
Q O
statistic O
. O
Results O
Eighteen O
out O
of O
432 O
available O
search O
output O
were O
eligible O
and O
included O
for O
this O
study O
. O
Of O
which O
13 O
and O
5 O
were O
WNV O
studies O
on O
humans O
and O
animals O
, O
respectively O
. O
Although O
61.5 O
% O
of O
the O
human O
studies O
had O
a O
low O
risk O
of O
bias O
, O
they O
all O
had O
high O
heterogeneity O
. O
The O
South B-LOC
West I-LOC
geopolitical O
zone O
of O
Nigeria B-LOC
had O
the O
highest O
pooled B-EPI
prevalence I-EPI
of O
anti O
- O
WNV O
immunoglobulin O
M O
( O
IgM O
; O
7.8 O
% O
in O
humans O
) O
. O
The O
pooled O
seroprevalence O
of O
anti O
- O
WNV O
IgM O
and O
immunoglobulin O
G O
( O
IgG O
) O
was O
7.1 O
% O
( O
95 O
% O
confidence O
interval O
[ O
CI O
] O
, O
5.9 O
to O
8.3 O
) O
and O
76.5 O
% O
( O
95 O
% O
CI O
, O
74.0 O
to O
78.8 O
) O
, O
respectively O
. O
The O
WNV O
RNA O
prevalence B-EPI
was O
1.9 O
% O
( O
95 O
% O
CI O
, O
1.4 O
to O
2.9 O
) O
, O
while O
14.3 O
% O
( O
95 O
% O
CI O
, O
12.9 O
to O
15.8 O
) O
had O
WNV O
- O
neutralizing O
antibodies O
. O
In O
animals O
, O
the O
pooled O
seroprevalence O
of O
anti O
- O
WNV O
IgM O
and O
IgG O
was O
90.3 O
% O
( O
95 O
% O
CI O
, O
84.3 O
to O
94.6 O
) O
and O
3.5 O
% O
( O
95 O
% O
CI O
, O
1.9 O
to O
5.8 O
) O
, O
respectively O
, O
while O
20.0 O
% O
( O
95 O
% O
CI O
, O
12.9 O
to O
21.4 O
) O
had O
WNV O
- O
neutralizing O
antibodies O
. O
Age O
( O
odds O
ratio O
[ O
OR O
] O
, O
3.73 O
; O
95 O
% O
CI O
, O
1.87 O
to O
7.45 O
; O
p<0.001 O
) O
and O
level O
of O
education O
( O
no O
formal O
education O
: O
OR O
, O
4.31 O
; O
95 O
% O
CI O
, O
1.08 O
to O
17.2 O
; O
p<0.05 O
; O
primary O
: O
OR O
, O
7.29 O
; O
95 O
% O
CI O
, O
1.80 O
to O
29.6 O
; O
p<0.01 O
) O
were O
significant O
risk O
factors O
for O
WNV O
IgM O
seropositivity O
in O
humans O
. O
Conclusions O
The O
findings O
of O
this O
study O
highlight O
the O
endemicity O
of O
WNV O
in O
animals O
and O
humans O
in O
Nigeria B-LOC
and O
underscore O
the O
need O
for O
the O
One O
Health O
prevention O
and O
control O
approach O
. O
Both O
axial O
spondyloarthritis O
( O
axSpA O
) O
and O
idiopathic O
inflammatory O
myopathy O
( O
IIM O
) O
are O
infrequent O
, O
and O
their O
coexistence O
is O
even O
rarer O
; O
there O
are O
a O
few O
reported O
cases O
in O
the O
literature O
. O
The O
aim O
of O
this O
study O
was O
to O
assess O
their O
association O
and O
clinical O
and O
laboratory O
features O
in O
our O
patients O
. O
The O
clinical O
data O
of O
patients O
with O
axSpA O
and O
IIM O
diagnosed O
in O
China B-LOC
- O
Japan O
Friendship O
Hospital O
from O
July O
2015 O
to O
February O
2019 O
were O
retrospectively O
analyzed O
. O
This O
study O
included O
7 O
patients O
with O
axSpA O
who O
met O
the O
IIM O
criteria O
, O
including O
3 O
males O
and O
4 O
females O
. O
The O
age O
of O
onset O
was O
16 O
to O
39 O
years O
. O
Four O
patients O
were O
HLA O
- O
B27 O
positive O
, O
and O
three O
were O
negative O
. O
All O
patients O
were O
first O
diagnosed O
as O
axSpA O
, O
and O
then O
IIM O
was O
detected O
after O
0.5 O
- O
20 O
years O
( O
mean O
± O
SD O
, O
9.9 O
± O
5.0 O
years O
) O
. O
After O
being O
diagnosed O
to O
have O
axSpA O
and O
IIM O
, O
those O
patients O
were O
given O
prednisone O
and O
immunosuppressant O
drugs O
, O
and O
their O
symptoms O
gradually O
improved O
. O
Our O
study O
provides O
further O
evidence O
of O
the O
coexistence O
of O
IIM O
with O
axSpA. O
In O
patients O
with O
axSpA O
who O
have O
skin O
rash O
, O
interstitial O
lung O
disease O
( O
ILD O
) O
, O
myalgia O
, O
or O
muscle O
weakness O
, O
we O
should O
suspect O
that O
they O
may O
have O
IIM O
. O
Summary O
Multiple O
endocrine O
neoplasia O
type O
1 O
( O
MEN1 O
) O
is O
a O
rare O
inherited O
endocrine O
disorder O
with O
a O
high O
rate O
of O
penetrance O
. O
The O
incidence B-EPI
of O
MEN1 O
is O
1/30,000 B-STAT
in O
the O
general O
population O
; O
however O
, O
it O
is O
quite O
rare O
for O
a O
patient O
to O
present O
for O
medical O
attention O
with O
MEN1 O
for O
the O
first O
time O
in O
pregnancy O
. O
Primary O
hyperparathyroidism O
( O
PHPT O
) O
is O
one O
of O
the O
most O
common O
features O
of O
MEN1 O
. O
The O
incidence B-EPI
of O
PHPT O
occurring O
in O
pregnancy O
is O
1 B-STAT
% I-STAT
. O
Despite O
advances O
in O
the O
medical O
, O
surgical O
and O
obstetric O
care O
over O
the O
years O
, O
management O
of O
this O
condition O
during O
pregnancy O
may O
be O
challenging O
. O
It O
can O
be O
difficult O
to O
identify O
pregnant O
women O
with O
PHPT O
requiring O
intervention O
and O
to O
monitor O
safely O
. O
Hypercalcemia O
can O
result O
in O
significant O
maternal O
and O
fetal O
adverse O
outcomes O
including O
: O
miscarriage O
, O
intrauterine O
growth O
restriction O
, O
preterm O
delivery O
, O
neonatal O
hypocalcaemia O
, O
pre O
- O
eclampsia O
and O
maternal O
nephrolithiasis O
. O
Herein O
, O
we O
present O
a O
case O
study O
of O
a O
lady O
with O
a O
strong O
family O
history O
of O
MEN1 O
, O
who O
was O
biochemically O
proven O
to O
have O
PHPT O
and O
evidence O
of O
Zollinger O
Ellison O
Syndrome O
( O
ZE O
) O
on O
endoscopy O
. O
This O
patient O
delayed O
her O
assisted O
pregnancy O
plans O
for O
in O
vitro O
fertilization O
( O
IVF O
) O
until O
completion O
of O
the O
MEN1 O
workup O
; O
nevertheless O
, O
she O
spontaneously O
achieved O
an O
unplanned O
pregnancy O
. O
As O
a O
result O
, O
she O
required O
intervention O
with O
parathyroidectomy O
in O
the O
second O
trimester O
of O
her O
pregnancy O
as O
her O
calcium O
level O
continued O
to O
rise O
. O
This O
case O
study O
highlights O
the O
workup O
, O
follow O
up O
and O
management O
of O
MEN1 O
presenting O
with O
PHPT O
and O
ZE O
in O
pregnancy O
. O
Learning O
points O
Women O
of O
childbearing O
age O
who O
are O
suspected O
to O
have O
a O
diagnosis O
of O
primary O
hyperparathyroidism O
ideally O
should O
have O
genetic O
testing O
and O
avoid O
pregnancy O
until O
definitive O
plans O
are O
in O
place O
. O
Zollinger O
Ellison O
syndrome O
in O
pregnancy O
means O
off O
- O
label O
use O
of O
high O
dose O
of O
proton O
pump O
inhibitors O
( O
PPI O
) O
. O
Use O
of O
PPI O
in O
pregnancy O
is O
considered O
to O
be O
safe O
based O
on O
retrospective O
studies O
. O
Omeprazole O
, O
however O
, O
is O
FDA O
class O
C O
drug O
because O
of O
lack O
of O
large O
prospective O
studies O
or O
large O
case O
series O
during O
pregnancy O
. O
Calcium O
supplements O
in O
the O
form O
of O
calcium O
carbonate O
must O
be O
converted O
to O
calcium O
chloride O
by O
gastric O
acid O
in O
order O
to O
be O
absorbed O
, O
however O
, O
patients O
rendered O
achlorhydric O
as O
a O
result O
of O
PPI O
use O
will O
have O
impaired O
absorption O
of O
calcium O
. O
Therefore O
, O
use O
of O
calcium O
citrate O
might O
be O
considered O
a O
better O
option O
in O
this O
case O
. O
Background O
Mitochondrial O
diseases O
, O
also O
known O
as O
oxidative O
phosphorylation O
( O
OXPHOS O
) O
disorders O
, O
with O
a O
prevalence B-EPI
rate O
of O
1:5000 B-STAT
, O
are O
the O
most O
frequent O
inherited O
metabolic O
diseases O
. O
Leigh O
Syndrome O
French O
Canadian O
type O
( O
LSFC O
) O
, O
is O
caused O
by O
mutations O
in O
the O
nuclear O
gene O
( O
2p16 O
) O
leucine O
- O
rich O
pentatricopeptide O
repeat O
- O
containing O
( O
LRPPRC O
) O
. O
It O
is O
an O
autosomal O
recessive O
neurogenetic O
OXPHOS O
disorder O
, O
phenotypically O
distinct O
from O
other O
types O
of O
Leigh O
syndrome O
, O
with O
a O
carrier O
frequency O
up O
to O
1:23 B-STAT
and O
an O
incidence B-EPI
of O
1:2063 B-STAT
in O
the O
Saguenay O
- O
Lac O
- O
St O
Jean O
region O
of O
Quebec B-LOC
. O
Recently O
, O
LSFC O
has O
also O
been O
reported O
outside O
the O
French O
- O
Canadian O
population O
. O
Patient O
presentation O
We O
report O
a O
male O
Italian O
( O
Sicilian O
) O
child O
, O
born O
preterm O
at O
28 B-STAT
+ I-STAT
6/7 I-STAT
weeks O
gestation O
, O
carrying O
a O
novel O
LRPPRC O
compound O
heterozygous O
mutation O
, O
with O
facial O
dysmorphisms O
, O
neonatal O
hypotonia O
, O
non O
- O
epileptic O
paroxysmal O
motor O
phenomena O
, O
and O
absent O
sucking O
- O
swallowing O
- O
breathing O
coordination O
requiring O
, O
at O
4.5 O
months O
, O
a O
percutaneous O
endoscopic O
gastrostomy O
tube O
placement O
. O
At O
5 O
months O
brain O
Magnetic O
Resonance O
Imaging O
showed O
diffuse O
cortical O
atrophy O
, O
hypoplasia O
of O
corpus O
callosum O
, O
cerebellar O
vermis O
hypoplasia O
, O
and O
unfolded O
hippocampi O
. O
Both O
auditory O
and O
visual O
evoked O
potentials O
were O
pathological O
. O
In O
the O
following O
months O
Video O
EEG O
confirmed O
the O
persistence O
of O
sporadic O
non O
epileptic O
motor O
phenomena O
. O
No O
episode O
of O
metabolic O
decompensation O
, O
acidosis O
or O
ketosis O
, O
frequently O
observed O
in O
LSFC B-LOC
has O
been O
reported O
. O
Actually O
, O
aged O
14 O
months O
corrected O
age O
for O
prematurity O
, O
the O
child O
shows O
a O
severe O
global O
developmental O
delay O
. O
Metabolic O
investigations O
and O
array O
Comparative O
Genomic O
Hybridization O
( O
aCGH O
) O
results O
were O
normal O
. O
Whole O
- O
exome O
sequencing O
( O
WES O
) O
found O
a O
compound O
heterozygous O
mutation O
in O
the O
LRPPRC O
gene O
, O
c.1921 O
- O
7A O
> O
G O
and O
c.2056A O
> O
G O
( O
p. O
Ile686Val O
) O
, O
splicing O
- O
site O
and O
missense O
variants O
, O
inherited O
from O
the O
mother O
and O
the O
father O
, O
respectively O
. O
Conclusions O
We O
first O
characterized O
the O
clinical O
and O
molecular O
features O
of O
a O
novel O
LRPPRC O
variant O
in O
a O
male O
Sicilian O
child O
with O
early O
onset O
encephalopathy O
and O
psychomotor O
impairment O
. O
Our O
patient O
showed O
a O
phenotype O
characterized O
by O
a O
severe O
neurodevelopmental O
delay O
and O
absence O
of O
metabolic O
decompensation O
attributable O
to O
a O
probable O
residual O
enzymatic O
activity O
. O
LRPPRC O
is O
a O
rare O
cause O
of O
metabolic O
encephalopathy O
outside O
of O
Québec B-LOC
. O
Our O
patient O
adds O
to O
and O
broaden O
the O
spectrum O
of O
LSFC O
phenotypes O
. O
WES O
analysis O
is O
a O
pivotal O
genetic O
test O
and O
should O
be O
performed O
in O
infants O
and O
children O
with O
hypotonia O
and O
developmental O
delay O
in O
whom O
metabolic O
investigations O
and O
aCGH O
are O
normal O
. O
We O
present O
a O
case O
report O
of O
a O
32 O
- O
year O
- O
old O
woman O
diagnosed O
with O
opticomyelitis O
of O
Devic O
( O
OMD O
) O
and O
systemic O
lupus O
erythematosus O
( O
SLE O
) O
. O
The O
onset O
of O
neurological O
symptoms O
was O
with O
optic O
neuritis O
. O
Five O
months O
later O
the O
neurological O
deficit O
progressed O
within O
a O
few O
days O
to O
lower O
paraplegia O
and O
upper O
paraparesis O
, O
retention O
of O
urine O
and O
faeces O
, O
impaired O
somatic O
and O
deep O
sensation O
below O
the O
level O
of O
Th1 O
dermatome O
. O
The O
results O
from O
laboratory O
investigations O
confirmed O
anaemic O
syndrome O
, O
increased O
urea O
and O
creatinine O
, O
hypoproteinemia O
and O
severe O
proteinuria O
. O
The O
results O
from O
CSF O
investigations O
demonstrated O
hyperproteinorachia O
with O
extremely O
high O
Ig O
fractions O
. O
Serum O
and O
CSF O
oligoclonal O
bands O
and O
positive O
serum O
Aquaporin O
IgG O
32 O
times O
higher O
than O
the O
upper O
referent O
limit O
were O
found O
. O
The O
association O
with O
SLE O
was O
confirmed O
by O
the O
increased O
levels O
of O
total O
ANA O
and O
anti O
- O
ds O
- O
DNA O
ANA O
. O
MRT O
visualized O
the O
spinal O
cord O
as O
non O
- O
homogenously O
hypointense O
on O
T1 O
and O
extremely O
hyperintense O
on O
FLAIR O
sequences O
through O
its O
whole O
length O
up O
to O
the O
bulbar O
- O
pontine O
region O
. O
The O
MRT O
findings O
and O
the O
serum O
Aquaporin O
IgG O
confirmed O
the O
diagnosis O
OMD O
. O
The O
patient O
was O
treated O
with O
intravenous O
immunomodulating O
agents O
. O
We O
consider O
the O
presented O
case O
of O
special O
interest O
because O
of O
the O
comorbidity O
of O
an O
aggressive O
autoimmune O
systemic O
and O
an O
organ O
- O
specific O
disease O
of O
the O
central O
nervous O
system O
. O
Osteogenesis O
imperfecta O
( O
OI O
) O
is O
a O
heritable O
disorder O
that O
mainly O
affects O
the O
skeleton O
. O
The O
inheritance O
is O
mostly O
autosomal O
dominant O
and O
associated O
to O
mutations O
in O
one O
of O
the O
two O
genes O
, O
COL1A1 O
and O
COL1A2 O
, O
encoding O
for O
the O
type O
I O
collagen O
α O
chains O
. O
According O
to O
more O
than O
1500 O
described O
mutation O
sites O
and O
to O
outcome O
spanning O
from O
very O
mild O
cases O
to O
perinatal O
- O
lethality O
, O
OI O
is O
characterized O
by O
a O
wide O
genotype O
/ O
phenotype O
heterogeneity O
. O
In O
order O
to O
identify O
common O
affected O
molecular O
- O
pathways O
and O
disease O
biomarkers O
in O
OI O
probands O
with O
different O
mutations O
and O
lethal O
or O
surviving O
phenotypes O
, O
primary O
fibroblasts O
from O
dominant O
OI O
patients O
, O
carrying O
COL1A1 O
or O
COL1A2 O
defects O
, O
were O
investigated O
by O
applying O
a O
Tandem O
Mass O
Tag O
labeling O
- O
Liquid O
Chromatography O
- O
Tandem O
Mass O
Spectrometry O
( O
TMT O
LC O
- O
MS O
/ O
MS O
) O
proteomics O
approach O
and O
bioinformatic O
tools O
for O
comparative O
protein O
- O
abundance O
profiling O
. O
While O
no O
difference O
in O
α1 O
or O
α2 O
abundance O
was O
detected O
among O
lethal O
( O
type O
II O
) O
and O
not O
- O
lethal O
( O
type O
III O
) O
OI O
patients O
, O
17 O
proteins O
, O
with O
key O
effects O
on O
matrix O
structure O
and O
organization O
, O
cell O
signaling O
, O
and O
cell O
and O
tissue O
development O
and O
differentiation O
, O
were O
significantly O
different O
between O
type O
II O
and O
type O
III O
OI O
patients O
. O
Among O
them O
, O
some O
non O
- O
collagenous O
extracellular O
matrix O
( O
ECM O
) O
proteins O
( O
e.g. O
, O
decorin O
and O
fibrillin-1 O
) O
and O
proteins O
modulating O
cytoskeleton O
( O
e.g. O
, O
nestin O
and O
palladin O
) O
directly O
correlate O
to O
the O
severity O
of O
the O
disease O
. O
Their O
defective O
presence O
may O
define O
proband O
- O
failure O
in O
balancing O
aberrances O
related O
to O
mutant O
collagen O
. O
Objective O
To O
demonstrate O
that O
delayed O
cord O
clamping O
( O
DCC O
) O
is O
safe O
in O
mothers O
with O
confirmed O
SARS O
- O
CoV-2 O
infection O
. O
Design O
, O
setting O
and O
participants O
Prospective O
observational O
study O
involving O
epidemiological O
information O
from O
403 O
pregnant O
women O
with O
SARS O
- O
CoV-2 O
between O
1 B-STAT
March O
and O
31 O
May O
2020 O
. O
Data O
were O
collected O
from O
70 O
centres O
that O
participate O
in O
the O
Spanish O
Registry O
of O
COVID-19 O
. O
Methods O
Patients O
' O
information O
was O
collected O
from O
their O
medical O
chart O
. O
Main O
outcomes O
and O
measures O
The O
rate O
of O
perinatal O
transmission O
of O
SARS O
- O
CoV-2 O
and O
development O
of O
the O
infection O
in O
neonates O
within O
14 O
days O
postpartum O
. O
Results O
The O
early O
cord O
clamping O
( O
ECC O
) O
group O
consisted O
of O
231 O
infants O
( O
57.3 O
% O
) O
and O
the O
DCC O
group O
consisted O
of O
172 O
infants O
( O
42.7 O
% O
) O
. O
Five O
positive O
newborns O
( O
1.7 O
% O
of O
total O
tests O
performed O
) O
were O
identified O
with O
the O
nasopharyngeal O
PCR O
tests O
performed O
in O
the O
first O
12 O
hours O
postpartum O
, O
two O
from O
the O
ECC O
group O
( O
1.7 O
% O
) O
and O
three O
from O
the O
DCC O
group O
( O
3.6 O
% O
) O
. O
No O
significant O
differences O
between O
groups O
were O
found O
regarding O
neonatal O
tests O
for O
SARS O
- O
CoV-2 O
. O
No O
confirmed O
cases O
of O
vertical O
transmission O
were O
detected O
. O
The O
percentage O
of O
mothers O
who O
made O
skin O
- O
to O
- O
skin O
contact O
within O
the O
first O
24 O
hours O
after O
delivery O
was O
significantly O
higher O
in O
the O
DCC O
group O
( O
84.3 O
% O
versus O
45.9 O
% O
) O
. O
Breastfeeding O
in O
the O
immediate O
postpartum O
period O
was O
also O
significantly O
higher O
in O
the O
DCC O
group O
( O
77.3 O
% O
versus O
50.2 O
% O
) O
. O
Conclusions O
The O
results O
of O
our O
study O
show O
no O
differences O
in O
perinatal O
outcomes O
when O
performing O
ECC O
or O
DCC O
, O
and O
skin O
- O
to O
- O
skin O
contact O
, O
or O
breastfeeding O
. O
Tweetable O
abstract O
This O
study O
demonstrates O
that O
delayed O
cord O
clamping O
is O
safe O
in O
mothers O
with O
confirmed O
SARS O
- O
CoV-2 O
infection O
. O
Stroke O
is O
a O
leading O
cause O
of O
disability O
and O
mortality O
all O
over O
the O
world O
. O
Due O
to O
an O
aging O
population O
, O
the O
incidence B-EPI
of O
stroke O
is O
rising O
significantly O
, O
which O
has O
led O
to O
devastating O
consequences O
for O
patients O
. O
In O
addition O
to O
traditional O
risk O
factors O
such O
as O
age O
, O
hypertension O
, O
hyperlipidemia O
, O
diabetes O
and O
atrial O
fibrillation O
, O
sleep O
disorders O
, O
as O
independent O
modifiable O
risk O
factors O
for O
stroke O
, O
have O
been O
highlighted O
increasingly O
. O
In O
this O
review O
, O
we O
provide O
an O
overview O
of O
common O
types O
of O
current O
sleep O
disturbances O
in O
cerebrovascular O
diseases O
, O
including O
insomnia O
, O
hypersomnia O
, O
breathing O
- O
related O
sleep O
disorders O
, O
and O
parasomnias O
. O
Moreover O
, O
evidence O
- O
based O
clinical O
therapeutic O
strategies O
and O
pitfalls O
of O
specific O
sleep O
disorders O
after O
stroke O
are O
discussed O
. O
We O
also O
review O
the O
neurobiological O
mechanisms O
of O
these O
treatments O
as O
well O
as O
their O
effects O
on O
stroke O
. O
Since O
depression O
after O
stroke O
is O
so O
prevalent B-EPI
and O
closely O
related O
to O
sleep O
disorders O
, O
treatments O
of O
post O
- O
stroke O
depression O
are O
also O
briefly O
mentioned O
in O
this O
review O
article O
. O
Metabolic O
liver O
diseases O
( O
MLD O
) O
are O
an O
important O
group O
of O
disorders O
presenting O
with O
neonatal O
cholestasis O
( O
NC B-LOC
) O
. O
The O
spectrum O
of O
liver O
involvement O
is O
wide O
and O
the O
presumptive O
diagnosis O
is O
traditionally O
based O
on O
clinical O
and O
laboratory O
findings O
. O
Recently O
, O
next O
- O
generation O
sequencing O
( O
NGS O
) O
panels O
have O
emerged O
as O
an O
appealing O
tool O
to O
diagnose O
neonatal O
/ O
infantile O
cholestatic O
disorders O
. O
The O
aim O
of O
this O
study O
was O
to O
identify O
clinical O
phenotypes O
of O
liver O
injury O
and O
contribute O
to O
find O
a O
diagnostic O
methodology O
that O
integrates O
new O
molecular O
diagnostic O
tools O
. O
We O
retrospectively O
analyzed O
the O
clinical O
and O
biochemical O
features O
of O
16 O
patients O
with O
MLD O
and O
NC B-LOC
. O
Patients O
were O
categorized O
into O
three O
groups O
: O
A O
- O
NC O
with O
liver O
failure O
( O
N O
= O
8) O
: O
tyrosinemia O
type O
I O
( O
n O
= O
2 O
) O
, O
classic O
galactosemia O
( O
n O
= O
5 O
) O
, O
mitochondrial O
DNA O
depletion O
syndrome O
( O
n O
= O
1 O
) O
; O
B O
- O
NC O
evolving O
with O
chronic O
liver O
disease O
( O
N O
= O
5 O
): O
argininemia O
( O
n O
= O
2 O
) O
; O
mitochondrial O
cytopathy O
( O
n O
= O
1 O
) O
; O
congenital O
disorders O
of O
glycosylation O
type O
Ia O
( O
n O
= O
1 B-STAT
) I-STAT
; I-STAT
Zellweger O
syndrome O
( O
n O
= O
1 O
) O
; O
and O
C O
- O
transient O
NC B-LOC
( O
N O
= O
3 O
): O
Niemann O
- O
Pick O
type O
C O
( O
n O
= O
2 O
) O
, O
citrullinemia O
type O
II O
( O
n O
= O
1).Conclusion O
: O
MLD O
presenting O
with O
NC B-LOC
can O
be O
categorized O
into O
three O
main O
clinical O
phenotypes O
of O
liver O
injury O
. O
We O
highlight O
transient O
NC B-LOC
as O
a O
clue O
for O
MLD O
that O
must O
be O
pursued O
. O
New O
molecular O
diagnostic O
tools O
can O
play O
a O
key O
role O
, O
but O
application O
criteria O
must O
be O
established O
to O
make O
them O
cost O
- O
effective O
. O
What O
is O
Known O
: O
• O
Metabolic O
liver O
diseases O
are O
an O
important O
group O
of O
disorders O
presenting O
with O
neonatal O
cholestasis O
. O
• O
The O
diagnostic O
approach O
is O
challenging O
and O
traditionally O
based O
on O
clinical O
and O
laboratory O
findings O
. O
Next O
- O
generation O
sequencing O
is O
a O
recent O
and O
rapidly O
developing O
tool O
in O
pediatric O
hepatology O
. O
What O
is O
New O
: O
• O
We O
provide O
a O
liver O
- O
targeted O
characterization O
of O
metabolic O
liver O
diseases O
presenting O
with O
neonatal O
cholestasis O
, O
categorizing O
them O
into O
three O
clinical O
phenotypes O
that O
may O
narrow O
the O
diagnostic O
possibilities O
. O
• O
A O
clinical O
decision O
- O
making O
algorithm O
is O
proposed O
, O
in O
which O
the O
NGS O
technology O
is O
integrated O
. O
Many O
adrenocortical O
diseases O
are O
more O
prevalent B-EPI
in O
women O
than O
in O
men O
, O
but O
the O
reasons O
underlying O
this O
sex O
bias O
are O
still O
unknown O
. O
Recent O
studies O
involving O
gonadectomy O
and O
sex O
hormone O
replacement O
experiments O
in O
mice O
have O
shed O
some O
light O
onto O
the O
molecular O
basis O
of O
sexual O
dimorphism O
in O
the O
adrenal O
cortex O
. O
Indeed O
, O
it O
has O
been O
shown O
that O
gonadal O
hormones O
influence O
many O
aspects O
of O
adrenal O
physiology O
, O
ranging O
from O
stem O
cell O
- O
dependent O
tissue O
turnover O
to O
steroidogenesis O
and O
X O
- O
zone O
dynamics O
. O
This O
article O
reviews O
current O
knowledge O
on O
adrenal O
cortex O
sexual O
dimorphism O
and O
the O
potential O
mechanisms O
underlying O
sex O
hormone O
influence O
of O
adrenal O
homeostasis O
. O
Both O
topics O
are O
expected O
to O
contribute O
to O
personalized O
and O
novel O
therapeutic O
approaches O
in O
the O
future O
. O
Background O
The O
European O
Rare O
Kidney O
Disease O
Reference O
Network O
( O
ERKNet O
) O
recently O
established O
ERKReg O
, O
a O
Web O
- O
based O
registry O
for O
all O
patients O
with O
rare O
kidney O
diseases O
. O
The O
main O
objectives O
of O
this O
core O
registry O
are O
to O
generate O
epidemiological O
information O
, O
identify O
current O
patient O
cohort O
for O
clinical O
research O
, O
explore O
diagnostic O
and O
therapeutic O
management O
practices O
, O
and O
monitor O
treatment O
performance O
and O
patient O
's O
outcomes O
. O
The O
registry O
has O
a O
modular O
design O
that O
allows O
to O
integrate O
comprehensive O
disease O
- O
specific O
registries O
as O
extensions O
to O
the O
core O
database O
. O
The O
diagnosis O
( O
Orphacode O
) O
and O
diagnostic O
information O
( O
clinical O
, O
imaging O
, O
histopathological O
, O
biochemical O
, O
immunological O
and O
genetic O
) O
are O
recorded O
. O
Anthropometric O
, O
kidney O
function O
, O
and O
disease O
- O
specific O
management O
and O
outcome O
items O
informing O
a O
set O
of O
61 O
key O
performance O
indicators O
( O
KPIs O
) O
are O
obtained O
annually O
. O
Data O
quality O
is O
ensured O
by O
automated O
plausibility O
checks O
upon O
data O
entry O
and O
regular O
offline O
database O
checks O
prompting O
queries O
. O
Centre O
KPI O
statistics O
and O
benchmarking O
are O
calculated O
automatically O
. O
Results O
Within O
the O
first O
24 O
months O
since O
its O
launch O
, O
7607 O
patients O
were O
enrolled O
to O
the O
registry O
at O
45 O
pediatric O
and O
12 O
specialized O
adult O
nephrology O
units O
from O
21 O
countries O
. O
A O
kidney O
disease O
diagnosis O
had O
been O
established O
in O
97.1 O
% O
of O
these O
patients O
at O
time O
of O
enrolment O
. O
While O
199 O
individual O
disease O
entities O
were O
reported O
by O
Orphacode O
, O
50 O
% O
of O
the O
cohort O
could O
be O
classified O
with O
11 B-STAT
, O
80 O
% O
with O
43 O
and O
95 O
% O
with O
92 O
codes O
. O
Two O
kidney O
diagnoses O
were O
assigned O
in O
6.5 O
% O
of O
patients O
; O
5.9 O
% O
suffered O
from O
syndromic O
disease O
. O
Whereas O
glomerulopathies O
( O
54.8 O
% O
) O
and O
ciliopathies O
including O
autosomal O
dominant O
polycystic O
kidney O
disease O
( O
ADPKD O
) O
( O
31.5 O
% O
) O
were O
the O
predominant O
disease O
groups O
among O
adults O
, O
the O
pediatric O
disease O
spectrum O
encompassed O
congenital O
anomalies O
of O
the O
kidney O
and O
urinary O
tract O
( O
CAKUT O
) O
( O
33.7 O
% O
) O
, O
glomerulopathies O
( O
30.7 O
% O
) O
, O
ciliopathies O
( O
14.0 O
% O
) O
, O
tubulopathies O
( O
9.2 O
% O
) O
, O
thrombotic O
microangiopathies O
( O
5.6 O
% O
) O
, O
and O
metabolic O
nephropathies O
( O
4.1 O
% O
) O
. O
Genetically O
confirmed O
diagnoses O
were O
reported O
in O
24 O
% O
of O
all O
pediatric O
and O
12 O
% O
adult O
patients O
, O
whereas O
glomerulopathies O
had O
been O
confirmed O
by O
kidney O
biopsy O
in O
80.4 O
% O
adult O
versus O
38.5 O
% O
pediatric O
glomerulopathy O
cases O
. O
Conclusions O
ERKReg O
is O
a O
rapidly O
growing O
source O
of O
epidemiological O
information O
and O
patient O
cohorts O
for O
clinical O
research O
, O
and O
an O
innovative O
tool O
to O
monitor O
management O
quality O
and O
patient O
outcomes O
. O
Pseudoachondroplasia B-LOC
( O
PSACH O
) O
is O
an O
autosomal O
dominant O
skeletal O
dysplasia O
with O
an O
estimated B-EPI
incidence I-EPI
of O
~1/60000 O
that O
is O
characterized O
by O
disproportionate O
short O
stature O
, O
brachydactyly O
, O
joint O
laxity O
, O
and O
early O
- O
onset O
osteoarthritis O
. O
COMP O
encodes O
the O
cartilage O
oligomeric O
matrix O
protein O
, O
which O
is O
expressed O
predominantly O
in O
the O
extracellular O
matrix O
( O
ECM O
) O
surrounding O
the O
cells O
that O
make O
up O
cartilage O
, O
ligaments O
, O
and O
tendons O
. O
Mutations O
in O
COMP O
are O
known O
to O
give O
rise O
to O
PSACH O
. O
In O
this O
study O
, O
we O
identified O
a O
novel O
nucleotide O
mutation O
( O
NM_000095.2 O
: O
c.1317C O
> O
G O
, O
p. O
D439E O
) O
in O
COMP O
responsible O
for O
PSACH O
in O
a O
Chinese O
family O
by O
employing O
whole O
- O
exome O
sequencing O
( O
WES O
) O
and O
built O
the O
structure O
model O
of O
the O
mutant O
protein O
to O
clarify O
its O
pathogenicity O
. O
The O
novel O
mutation O
cosegregated O
with O
the O
affected O
individuals O
. O
Our O
study O
expands O
the O
spectrum O
of O
COMP O
mutations O
and O
further O
provides O
additional O
genetic O
testing O
information O
for O
other O
PSACH O
patients O
. O
New O
born O
babies O
could O
suffer O
from O
multiple O
craniofacial O
abnormalities O
, O
such O
as O
Pierre O
Robin O
syndrome O
, O
which O
consists O
of O
micrognathia O
and O
relative O
macroglossia O
with O
or O
without O
cleft O
palate O
. O
Although O
Pierre O
Robin O
syndrome O
is O
well O
described O
in O
literature O
, O
only O
a O
few O
have O
mentioned O
its O
occurrence B-EPI
in O
identical O
twins O
. O
This O
paper O
presents O
a O
rare O
incident O
of O
full O
- O
term O
twin O
babies O
born O
with O
the O
sequence O
of O
Pierre O
Robin O
syndrome O
, O
which O
consists O
of O
micrognathia O
, O
cleft O
palate O
, O
and O
glossoptosis O
. O
Although O
it O
is O
a O
rare O
coincidence O
, O
Pierre O
Robin O
syndrome O
still O
can O
occur O
in O
identical O
twin O
babies O
. O
The O
treatment O
is O
a O
step O
- O
by O
- O
step O
approach O
, O
but O
all O
procedures O
are O
mainly O
directed O
to O
widening O
the O
pharyngeal O
space O
. O
Background O
Premarital O
sex O
practices O
and O
contraceptive O
prevalence B-EPI
rate O
( O
CPR O
) O
among O
unmarried O
women O
worldwide B-LOC
remain O
unclear O
, O
even O
though O
unmarried O
women O
tend O
to O
have O
multiple O
sex O
partners O
over O
time O
, O
which O
makes O
their O
sexual O
behaviors O
particularly O
important O
to O
the O
sexual O
and O
reproductive O
health O
of O
society O
more O
broadly O
. O
Methods O
We O
searched O
the O
MEDLINE O
, O
PubMed O
, O
and O
Google O
Scholar O
databases O
for O
relevant O
articles O
published O
between O
January O
1 O
, O
1999 O
and O
December O
31 O
, O
2018 O
. O
Data O
on O
prevalence B-EPI
of O
premarital O
sexual O
intercourse O
, O
use O
of O
highly O
prevalent B-EPI
contraceptive O
methods O
, O
as O
well O
as O
CPR O
overall O
and O
at O
first O
sexual O
intercourse O
were O
extracted O
and O
estimated O
using O
a O
DerSimonian- O
Laird O
random O
effects O
model O
. O
Results O
Of O
the O
3918 O
articles O
identified O
, O
37 O
covering O
19 O
countries O
were O
included O
. O
The O
estimated O
overall B-EPI
prevalence I-EPI
of O
premarital O
sexual O
intercourse O
was O
41.9 O
% O
( O
95%CI O
34.2 O
- O
49.6 O
% O
) O
. O
Pooled O
CPR O
was O
57.0 O
% O
( O
95%CI O
44.3 O
- O
69.8 O
% O
) O
overall O
and O
57.6 O
% O
( O
95 O
% O
CI O
39.5- O
75.6 O
% O
) O
at O
first O
intercourse O
. O
The O
overall B-EPI
prevalence I-EPI
of O
condom O
use O
was O
51.2 O
% O
( O
95%CI O
42.7 O
- O
59.7 O
% O
) O
, O
followed O
by O
oral O
contraceptives O
( O
20.5 O
% O
, O
95%CI O
13.7 O
- O
27.3 O
% O
) O
, O
withdrawal O
( O
12.7 O
% O
, O
95%CI O
9.4 O
- O
15.9 O
% O
) O
, O
and O
rhythm O
( O
12.1 O
% O
, O
95%CI O
6.7 O
- O
17.4 O
% O
) O
. O
Conclusion O
The O
findings O
of O
this O
global O
study O
indicate O
worrying O
trends O
in O
unprotected O
intercourse O
and O
contraceptive O
practices O
, O
suggesting O
the O
need O
for O
greater O
attention O
and O
resources O
aimed O
at O
educating O
unmarried O
adolescent O
women O
about O
sexual O
and O
reproductive O
health O
. O
Systematic O
review O
registration O
number O
CRD42019132736 O
. O
Charcot O
- O
Marie O
- O
Tooth O
disease O
( O
CMT O
) O
is O
a O
group O
of O
inherited O
neurological O
disorders O
of O
the O
peripheral O
nervous O
system O
. O
CMT O
is O
subdivided O
into O
two O
main O
types O
: O
a O
demyelinating O
form O
, O
known O
as O
CMT1 O
, O
and O
an O
axonal O
form O
, O
known O
as O
CMT2 O
. O
Nearly O
30 O
genes O
have O
been O
identified O
as O
a O
cause O
of O
CMT2 O
. O
One O
of O
these O
is O
the O
' O
dehydrogenase O
E1 O
and O
transketolase O
domain O
containing O
1 O
' O
( O
DHTKD1 O
) O
gene O
. O
We O
previously O
demonstrated O
that O
a O
nonsense O
mutation O
[ O
c.1455 O
T O
> O
G O
( O
p. O
Y485 O
* O
) O
] O
in O
exon O
8 O
of O
DHTKD1 O
is O
one O
of O
the O
disease O
- O
causing O
mutations O
in O
CMT2Q O
( O
MIM O
615025 O
) O
. O
The O
aim O
of O
the O
current O
study O
was O
to O
investigate O
whether O
human O
disease O
- O
causing O
mutations O
in O
the O
Dhtkd1 O
gene O
cause O
CMT2Q O
phenotypes O
in O
a O
mouse O
model O
in O
order O
to O
investigate O
the O
physiological O
function O
and O
pathogenic O
mechanisms O
associated O
with O
mutations O
in O
the O
Dhtkd1 O
gene O
in O
vivo O
. O
Therefore O
, O
we O
generated O
a O
knock O
- O
in O
mouse O
model O
with O
the O
Dhtkd1 O
Y486 O
* O
point O
mutation O
. O
We O
observed O
that O
the O
Dhtkd1 O
expression O
level O
in O
sciatic O
nerve O
of O
knock O
- O
in O
mice O
was O
significantly O
lower O
than O
in O
wild O
- O
type O
mice O
. O
Moreover O
, O
a O
histopathological O
phenotype O
was O
observed O
, O
reminiscent O
of O
a O
peripheral O
neuropathy O
, O
including O
reduced O
large O
axon O
diameter O
and O
abnormal O
myelination O
in O
peripheral O
nerves O
. O
The O
knock O
- O
in O
mice O
also O
displayed O
clear O
sensory O
defects O
, O
while O
no O
abnormalities O
in O
the O
motor O
performance O
were O
observed O
. O
In O
addition O
, O
accumulation O
of O
mitochondria O
and O
an O
elevated O
energy O
metabolic O
state O
was O
observed O
in O
the O
knock O
- O
in O
mice O
. O
Taken O
together O
, O
our O
study O
indicates O
that O
the O
Dhtkd1 O
Y486 O
* O
knock O
- O
in O
mice O
partially O
recapitulate O
the O
clinical O
phenotypes O
of O
CMT2Q O
patients O
and O
we O
hypothesize O
that O
there O
might O
be O
a O
compensatory O
effect O
from O
the O
elevated O
metabolic O
state O
in O
the O
knock O
- O
in O
mice O
that O
enables O
them O
to O
maintain O
their O
normal O
locomotor O
function O
. O
Although O
geographic O
information O
system O
- O
based O
studies O
are O
particularly O
increasing O
in O
other O
sectors O
, O
few O
have O
embraced O
their O
full O
potential O
in O
health O
services O
allocation O
in O
Malaysia B-LOC
. O
This O
study O
aimed O
to O
produce O
a O
visual O
map O
on O
the O
distribution O
of O
smoking O
cessation O
clinics O
( O
SCCs O
) O
in O
Malaysia B-LOC
and O
analyze O
its O
pattern O
against O
the O
national O
population O
of O
smokers O
. O
SCC O
addresses O
were O
obtained O
from O
the O
government O
website O
and O
mapped O
using O
geographic O
information O
system O
tools O
. O
A O
total O
of O
199 O
and O
449 O
private O
and O
public O
SCCs O
was O
mapped O
throughout O
the O
country O
, O
respectively O
. O
The O
lowest O
SCC O
to O
smoker O
population O
ratio O
was O
in O
the O
state O
of O
Negeri O
Sembilan O
with O
1:3000 O
. O
The O
highest O
SCC O
to O
smoker O
population O
ratio O
was O
in O
Sabah B-LOC
with O
1 B-STAT
SCC I-STAT
for I-STAT
15 I-STAT
000 I-STAT
smokers O
. O
Almost O
70 O
% O
of O
SCCs O
were O
primary O
health O
clinics O
. O
Smoking O
cessation O
clinics O
were O
distributed O
throughout O
all O
the O
states O
in O
Malaysia B-LOC
except O
the O
state O
of O
Sabah B-LOC
. O
Background O
The O
incidence B-EPI
of O
hydrocephalus O
in O
the O
spinal O
muscular O
atrophy O
( O
SMA O
) O
population O
relative O
to O
the O
general O
population O
is O
currently O
unknown O
. O
Since O
the O
approval O
of O
nusinersen O
, O
an O
intrathecally O
administered O
drug O
for O
SMA O
, O
a O
small O
number O
of O
hydrocephalus O
cases O
among O
nusinersen O
users O
have O
been O
reported O
. O
Currently O
, O
the O
incidence B-EPI
of O
hydrocephalus O
in O
untreated O
SMA O
patients O
is O
not O
available O
, O
thereby O
making O
it O
difficult O
to O
determine O
if O
hydrocephalus O
is O
a O
side O
effect O
of O
nusinersen O
or O
part O
of O
SMA O
's O
natural O
history O
. O
This O
retrospective O
, O
matched O
cohort O
study O
used O
electronic O
health O
records O
( O
EHRs O
) O
to O
estimate O
and O
compare O
the O
incidence B-EPI
of O
hydrocephalus O
in O
both O
SMA O
patients O
and O
matched O
non O
- O
SMA O
controls O
in O
the O
time O
period O
prior O
to O
the O
approval O
of O
nusinersen O
. O
Methods O
The O
U.S. B-LOC
Optum O
® O
de O
- O
identified O
EHR O
database O
contains O
records O
for O
approximately O
100 O
million O
persons O
. O
The O
current O
study O
period O
spanned O
January O
1 O
, O
2007 O
- O
December O
22 O
, O
2016 O
. O
Patients O
with O
SMA O
were O
identified O
by O
one O
or O
more O
International O
Classification O
of O
Diseases O
( O
ICD)-9 O
and/or O
ICD-10 O
codes O
for O
SMA O
appearing O
as O
primary O
, O
admission O
, O
or O
discharge O
diagnoses O
, O
without O
a O
pregnancy O
diagnostic O
code O
in O
the O
1 O
- O
year O
time O
before O
and O
after O
the O
first O
occurrence B-EPI
of O
SMA O
. O
The O
first O
occurrence B-EPI
of O
SMA O
defined O
the O
index O
date O
and O
non O
- O
SMA O
controls O
were O
matched O
to O
cases O
. O
Incident O
cases O
of O
hydrocephalus O
were O
identified O
with O
one O
or O
more O
ICD-9 B-LOC
and/or O
ICD-10 O
code O
for O
any O
type O
of O
hydrocephalus O
following O
the O
index O
date O
. O
Hydrocephalus O
incidence B-EPI
rates O
per O
person O
- O
months O
and O
the O
incidence B-EPI
rate O
ratio O
comparing O
SMA O
cases O
with O
non O
- O
SMA O
controls O
were O
calculated O
. O
Results O
There O
were O
5354 O
SMA O
cases O
and O
an O
equal O
number O
of O
matched O
non O
- O
SMA O
controls O
. O
Incident O
hydrocephalus O
events O
were O
identified O
in O
42 O
SMA O
cases O
and O
9 O
non O
- O
SMA O
controls O
. O
Hydrocephalus O
incidence B-STAT
rates I-STAT
per I-STAT
100,000 I-STAT
person I-STAT
- O
months O
were O
15.5 O
( O
95 O
% O
CI O
: O
11.2 O
- O
20.9 O
) O
among O
SMA O
cases O
and O
3.3 O
( O
95 O
% O
CI O
: O
1.5 O
- O
6.3 O
) O
among O
non O
- O
SMA O
controls O
. O
The O
incidence B-EPI
rate O
ratio O
was O
4.7 O
( O
95 O
% O
CI O
: O
2.4 O
- O
10.2 O
) O
. O
Conclusions O
Based O
on O
this O
retrospective O
analysis O
utilizing O
US B-LOC
EHR O
data O
, O
SMA O
patients O
had O
an O
approximately O
fourfold O
increased O
risk O
of O
hydrocephalus O
compared O
with O
non O
- O
SMA O
controls O
in O
the O
era O
preceding O
nusinersen O
treatment O
. O
This O
study O
may O
assist O
in O
properly O
evaluating O
adverse O
events O
in O
nusinersen O
- O
treated O
SMA O
patients O
. O
Background O
Fulminant O
necrotising O
amoebic O
colitis O
( O
FulNAC O
) O
is O
an O
uncommon O
and O
grave O
complication O
of O
a O
very O
common O
infectious O
disease O
widely O
prevalent B-EPI
in O
tropical O
countries O
. O
In O
most O
of O
the O
cases O
reported O
, O
only O
a O
segment O
of O
large O
bowel O
was O
gangrenous O
. O
The O
involvement O
of O
the O
whole O
of O
the O
large O
bowel O
, O
as O
in O
our O
case O
, O
is O
very O
rare O
and O
has O
very O
high O
mortality O
ranging O
from O
55 O
% O
to O
100 O
% I-STAT
. O
Case O
Summary O
. O
A O
50 O
- O
year O
- O
old O
gentleman O
presented O
with O
an O
acute O
abdomen O
with O
a O
history O
of O
crampy O
abdominal O
pain O
and O
passage O
of O
blood O
mixed O
with O
mucous O
and O
loose O
stools O
. O
After O
resuscitation O
and O
investigations O
, O
the O
patient O
was O
taken O
up O
for O
laparotomy O
and O
the O
findings O
showed O
that O
the O
caecum O
was O
sloughed O
off O
and O
the O
entire O
large O
bowel O
had O
multiple O
perforations O
. O
Subtotal O
colectomy O
with O
ileostomy O
was O
performed O
. O
Histopathological O
examination O
showed O
evidence O
of O
pancolitis O
with O
multiple O
colonies O
of O
amoebic O
trophozoites O
. O
Discussion O
. O
Entamoeba O
histolytica O
is O
a O
protozoon O
that O
affects O
the O
large O
intestine O
and O
liver O
in O
humans O
. O
There O
can O
be O
various O
presentations O
of O
amoebiasis O
: O
asymptomatic O
infection O
( O
90 O
% O
) O
, O
symptomatic O
noninvasive O
infection O
( O
6 B-STAT
- O
8 O
% O
) O
, O
acute O
amoebic O
colitis O
( O
dysentery O
) O
, O
or O
fulminant O
colitis O
with O
perforation O
. O
FulNAC O
is O
an O
uncommon O
complication O
, O
difficult O
to O
diagnose O
and O
treat O
, O
and O
associated O
with O
a O
high O
mortality O
rate O
, O
ranging O
from O
55 O
% O
to O
100 O
% I-STAT
. O
Conclusion O
It O
is O
important O
to O
consider O
the O
possibility O
of O
fulminant O
necrotising O
amoebic O
colitis O
( O
FulNAC O
) O
as O
an O
uncommon O
and O
fatal O
complication O
of O
amoebiasis O
, O
especially O
in O
tropical O
countries O
, O
where O
amoebiasis O
is O
prevalent B-EPI
. O
Early O
diagnosis O
and O
antiamoebic O
treatment O
, O
along O
with O
urgent O
aggressive O
surgical O
resection O
of O
the O
involved O
segment O
and O
exteriorization O
of O
the O
proximal O
and O
distal O
bowel O
ends O
, O
are O
shown O
to O
reduce O
mortality O
. O
Tight O
junctions O
are O
cellular O
junctions O
that O
play O
a O
major O
role O
in O
the O
epithelial O
barrier O
function O
. O
In O
the O
inner O
ear O
, O
claudins O
, O
occludin O
, O
tricellulin O
, O
and O
angulins O
form O
the O
bicellular O
or O
tricellular O
binding O
of O
membrane O
proteins O
. O
In O
these O
, O
one O
type O
of O
claudin O
gene O
, O
CLDN14 O
, O
was O
reported O
to O
be O
responsible O
for O
human O
hereditary O
hearing O
loss O
, O
DFNB29 O
. O
Until O
now O
, O
nine O
pathogenic O
variants O
have O
been O
reported O
, O
and O
most O
phenotypic O
features O
remain O
unclear O
. O
In O
the O
present O
study O
, O
genetic O
screening O
for O
68 O
previously O
reported O
deafness O
causative O
genes O
was O
carried O
out O
to O
identify O
CLDN14 O
variants O
in O
a O
large O
series O
of O
Japanese O
hearing O
loss O
patients O
, O
and O
to O
clarify O
the O
prevalence B-EPI
and O
clinical O
characteristics O
of O
DFNB29 O
in O
the O
Japanese O
population O
. O
One O
patient O
had O
a O
homozygous O
novel O
variant O
( O
c.241C O
> O
T O
: O
p O
. O
Arg81Cys O
) O
( O
0.04 B-STAT
% I-STAT
: O
1/2549 B-STAT
) O
. O
The O
patient O
showed O
progressive O
bilateral O
hearing O
loss O
, O
with O
post O
- O
lingual O
onset O
. O
Pure O
- O
tone O
audiograms O
indicated O
a O
high O
- O
frequency O
hearing O
loss O
type O
, O
and O
the O
deterioration O
gradually O
spread O
to O
other O
frequencies O
. O
The O
patient O
showed O
normal O
vestibular O
function O
. O
Cochlear O
implantation O
improved O
the O
patient O
's O
sound O
field O
threshold O
levels O
, O
but O
not O
speech O
discrimination O
scores O
. O
This O
report O
indicated O
that O
claudin-14 O
is O
essential O
for O
maintaining O
the O
inner O
ear O
environment O
and O
suggested O
the O
possible O
phenotypic O
expansion O
of O
DFNB29 O
. O
This O
is O
the O
first O
report O
of O
a O
patient O
with O
a O
tight O
junction O
variant O
receiving O
a O
cochlear O
implantation O
. O
Age O
- O
related O
bone O
disorders O
such O
as O
osteoporosis O
or O
osteoarthritis O
are O
a O
major O
public O
health O
problem O
due O
to O
the O
functional O
disability O
for O
millions O
of O
people O
worldwide B-LOC
. O
Furthermore O
, O
fractures O
are O
associated O
with O
a O
higher O
degree O
of O
morbidity O
and O
mortality O
in O
the O
long O
term O
, O
which O
generates O
greater O
financial O
and O
health O
costs O
. O
As O
the O
world O
population O
becomes O
older O
, O
the O
incidence B-EPI
of O
this O
type O
of O
disease O
increases O
and O
this O
effect O
seems O
notably O
greater O
in O
those O
countries O
that O
present O
a O
more O
westernized O
lifestyle O
. O
Thus O
, O
increased O
efforts O
are O
directed O
toward O
reducing O
risks O
that O
need O
to O
focus O
not O
only O
on O
the O
prevention O
of O
bone O
diseases O
, O
but O
also O
on O
the O
treatment O
of O
persons O
already O
afflicted O
. O
Evidence O
is O
accumulating O
that O
dietary O
lipids O
play O
an O
important O
role O
in O
bone O
health O
which O
results O
relevant O
to O
develop O
effective O
interventions O
for O
prevent O
bone O
diseases O
or O
alterations O
, O
especially O
in O
the O
elderly O
segment O
of O
the O
population O
. O
This O
review O
focuses O
on O
evidence O
about O
the O
effects O
of O
dietary O
lipids O
on O
bone O
health O
and O
describes O
possible O
mechanisms O
to O
explain O
how O
lipids O
act O
on O
bone O
metabolism O
during O
aging O
. O
Little O
work O
, O
however O
, O
has O
been O
accomplished O
in O
humans O
, O
so O
this O
is O
a O
challenge O
for O
future O
research O
. O
Sjögren O
's O
syndrome O
( O
SS O
) O
is O
a O
common O
systemic O
autoimmune O
disease O
. O
SS O
usually O
occurs B-EPI
among O
middle O
- O
aged O
women O
with O
a O
peak O
incidence B-EPI
age O
of O
approximately O
50 O
years O
old O
. O
Kidney O
involvement O
is O
relatively O
uncommon O
in O
SS O
, O
which O
is O
mostly O
characterized O
as O
interstitial O
nephritis O
and O
may O
result O
in O
renal O
tubular O
acidosis O
( O
RTA O
) O
. O
But O
premature O
onset O
of O
SS O
seems O
to O
be O
prone O
to O
RTA O
. O
Here O
we O
reported O
four O
cases O
of O
premature O
onset O
SS O
who O
developed O
into O
RTA O
at O
a O
relatively O
young O
age O
and O
three O
of O
whom O
suffered O
from O
severe O
osteomalacia O
. O
All O
of O
them O
shared O
a O
disease O
onset O
under O
age O
eighteen O
. O
Two O
of O
them O
presented O
hypokalemic O
periodic O
paralysis O
initially O
, O
one O
presented O
purpura O
and O
one O
endured O
xerophthalmia O
at O
first O
place O
. O
Three O
of O
them O
complicated O
with O
osteomalacia O
under O
age O
thirty O
. O
All O
the O
4 O
cases O
did O
n't O
receive O
proper O
medical O
care O
in O
time O
due O
to O
a O
prolonged O
delay O
of O
diagnosis O
. O
We O
aim O
to O
raise O
the O
alarm O
over O
misdiagnosis O
/ O
underdiagnosis O
of O
the O
disorder O
among O
young O
people O
. O
Autosomal O
recessive O
interleukin-1 O
receptor O
- O
associated O
kinase O
( O
IRAK)-4 O
and O
myeloid O
differentiation O
factor O
( O
MyD)88 O
deficiencies O
impair O
Toll O
- O
like O
receptor O
( O
TLR)- B-LOC
and O
interleukin-1 O
receptor O
- O
mediated O
immunity O
. O
We O
documented O
the O
clinical O
features O
and O
outcome O
of O
48 O
patients O
with O
IRAK-4 O
deficiency O
and O
12 O
patients O
with O
MyD88 O
deficiency O
, O
from O
37 O
kindreds O
in O
15 O
countries O
. O
The O
clinical O
features O
of O
IRAK-4 O
and O
MyD88 O
deficiency O
were O
indistinguishable O
. O
There O
were O
no O
severe O
viral O
, O
parasitic O
, O
and O
fungal O
diseases O
, O
and O
the O
range O
of O
bacterial O
infections O
was O
narrow O
. O
Noninvasive O
bacterial O
infections O
occurred O
in O
52 O
patients O
, O
with O
a O
high O
incidence B-EPI
of O
infections O
of O
the O
upper O
respiratory O
tract O
and O
the O
skin O
, O
mostly O
caused O
by O
Pseudomonas O
aeruginosa O
and O
Staphylococcus O
aureus O
, O
respectively O
. O
The O
leading O
threat O
was O
invasive O
pneumococcal O
disease O
, O
documented O
in O
41 O
patients O
( O
68 O
% O
) O
and O
causing O
72 O
documented O
invasive O
infections O
( O
52.2 O
% O
) O
. O
P. O
aeruginosa O
and O
Staph O
. O
aureus O
documented O
invasive O
infections O
also O
occurred O
( O
16.7 O
% O
and O
16 O
% O
, O
respectively O
, O
in O
13 O
and O
13 O
patients O
, O
respectively O
) O
. O
Systemic O
signs O
of O
inflammation O
were O
usually O
weak O
or O
delayed O
. O
The O
first O
invasive O
infection O
occurred O
before O
the O
age O
of O
2 O
years O
in O
53 B-STAT
( O
88.3 O
% O
) O
and O
in O
the O
neonatal O
period O
in O
19 B-STAT
( O
32.7 O
% O
) O
patients O
. O
Multiple O
or O
recurrent O
invasive O
infections O
were O
observed O
in O
most O
survivors O
( O
n O
= O
36/50 O
, O
72%).Clinical O
outcome O
was O
poor O
, O
with O
24 O
deaths O
, O
in O
10 O
cases O
during O
the O
first O
invasive O
episode O
and O
in O
16 O
cases O
of O
invasive O
pneumococcal O
disease O
. O
However O
, O
no O
death O
and O
invasive O
infectious O
disease O
were O
reported O
in O
patients O
after O
the O
age O
of O
8 O
years O
and O
14 O
years O
, O
respectively O
. O
Antibiotic O
prophylaxis O
( O
n O
= O
34 O
) O
, O
antipneumococcal O
vaccination O
( O
n O
= O
31 O
) O
, O
and/or O
IgG O
infusion O
( O
n O
= O
19 O
) O
, O
when O
instituted O
, O
had O
a O
beneficial O
impact O
on O
patients O
until O
the O
teenage O
years O
, O
with O
no O
seemingly O
detectable O
impact O
thereafter O
. O
IRAK-4 O
and O
MyD88 O
deficiencies O
predispose O
patients O
to O
recurrent O
life O
- O
threatening O
bacterial O
diseases O
, O
such O
as O
invasive O
pneumococcal O
disease O
in O
particular O
, O
in O
infancy O
and O
early O
childhood O
, O
with O
weak O
signs O
of O
inflammation O
. O
Patients O
and O
families O
should O
be O
informed O
of O
the O
risk O
of O
developing O
life O
- O
threatening O
infections O
; O
empiric O
antibacterial O
treatment O
and O
immediate O
medical O
consultation O
are O
strongly O
recommended O
in O
cases O
of O
suspected O
infection O
or O
moderate O
fever O
. O
Prophylactic O
measures O
in O
childhood O
are O
beneficial O
, O
until O
spontaneous O
improvement O
occurs B-EPI
in O
adolescence O
. O
Methylmalonic O
acidemia O
/ O
aciduria O
( O
MMA O
) O
is O
a O
genetically O
heterogeneous O
group O
of O
inherited O
metabolic O
disorders O
biochemically O
characterized O
by O
the O
accumulation O
of O
methylmalonic O
acid O
. O
Isolated O
MMA O
is O
primarily O
caused O
by O
the O
deficiency O
of O
methylmalonyl O
- O
CoA O
mutase O
( O
MMA O
mut O
; O
EC O
5.4.99.2 O
) O
. O
A O
systematic O
literature O
review O
and O
a O
meta O
- O
analysis O
were O
undertaken O
to O
assess O
and O
compile O
published O
epidemiological O
data O
on O
MMA O
with O
a O
focus O
on O
the O
MMA O
mut O
subtype O
( O
OMIM O
# O
251000 O
) O
. O
Of O
the O
1114 O
identified O
records O
, O
227 O
papers O
were O
assessed O
for O
eligibility O
in O
full O
text O
, O
48 O
articles O
reported O
on O
disease O
epidemiology O
, O
and O
39 O
articles O
were O
included O
into O
the O
quantitative O
synthesis O
. O
Implementation O
of O
newborn O
screening O
in O
various O
countries O
has O
allowed O
for O
the O
estimation O
of O
birth O
prevalence B-EPI
of O
MMA O
and O
its O
isolated O
form O
. O
Meta O
- O
analysis O
pooled O
point O
estimates O
of O
MMA O
( O
all O
types O
) O
detection O
rates O
were O
0.79 O
, O
1.12 O
, O
1.22 O
and O
6.04 B-STAT
per I-STAT
100,000 I-STAT
newborns I-STAT
in O
Asia B-LOC
- I-LOC
Pacific I-LOC
, O
Europe B-LOC
, O
North B-LOC
America I-LOC
and O
the B-LOC
Middle I-LOC
East I-LOC
and O
North B-LOC
Africa I-LOC
( O
MENA O
) O
regions O
, O
respectively O
. O
The O
detection O
rate O
of O
isolated O
MMA O
was O
< B-STAT
1 I-STAT
per I-STAT
100,000 I-STAT
newborns I-STAT
in O
all O
regions O
with O
the O
exception O
of O
MENA O
where O
it O
approached B-STAT
6 I-STAT
per I-STAT
100,000 I-STAT
newborns I-STAT
. O
Few O
studies O
published O
data O
on O
the O
epidemiology O
of O
MMA O
mut O
, O
therefore O
no O
meta O
- O
analysis O
could O
have O
been O
performed O
on O
this O
subtype O
. O
Most O
of O
the O
identified O
papers O
reported O
birth O
prevalence B-EPI
estimates O
below O
1 B-STAT
per I-STAT
100,000 I-STAT
newborns I-STAT
for O
MMA O
mut O
. O
The O
systematic O
literature O
review O
clearly O
demonstrates O
that O
MMA O
and O
its O
subtypes O
are O
ultra O
- O
rare O
disorders O
. O
Background O
: O
Neuroendocrine O
tumors O
( O
NETs O
) O
are O
rare O
, O
but O
their O
worldwide B-LOC
incidence B-EPI
is O
gradually O
increasing O
. O
NETs O
are O
generally O
heterogeneous O
; O
however O
, O
in O
rare O
cases O
, O
they O
have O
been O
shown O
to O
change O
their O
phenotype O
( O
i.e. O
, O
nonfunctional O
to O
functional O
or O
one O
functional O
phenotype O
to O
the O
addition O
of O
another O
functional O
phenotype O
) O
. O
Here O
, O
we O
present O
two O
cases O
of O
liver O
metastatic O
NETs O
with O
phenotype O
transformation O
at O
the O
advanced O
stage O
that O
led O
to O
life O
- O
threatening O
events O
. O
Case O
presentation O
: O
A O
73 O
- O
year O
- O
old O
woman O
had O
a O
small O
intestinal O
nonfunctional O
NET O
with O
liver O
metastasis O
. O
After O
uncontrollable O
liver O
metastasis O
at O
the O
advanced O
stage O
, O
she O
developed O
duodenal O
perforation O
with O
hypergastremia O
. O
The O
patient O
was O
treated O
with O
octreotide O
and O
proton O
pump O
inhibitors O
and O
underwent O
endoscopic O
closure O
for O
duodenal O
perforation O
, O
but O
her O
general O
condition O
gradually O
deteriorated O
, O
and O
she O
died O
2 O
weeks O
after O
duodenal O
perforation O
. O
Another O
patient O
, O
a O
50 O
- O
year O
- O
old O
man O
, O
had O
a O
functional O
NET O
( O
gastrinoma O
) O
with O
liver O
metastasis O
and O
duodenal O
ulcer O
. O
After O
uncontrollable O
liver O
metastasis O
at O
the O
advanced O
stage O
, O
he O
developed O
hypoglycemia O
. O
Although O
octoreotide O
and O
diazoxide O
were O
administrated O
for O
hyperalimentation O
, O
his O
hypoglycemia O
was O
uncontrollable O
, O
and O
he O
died O
after O
4 O
months O
owing O
to O
general O
deterioration O
. O
Conclusion O
: O
The O
present O
cases O
show O
that O
advanced O
NETs O
with O
treatment O
- O
uncontrollable O
liver O
metastasis O
can O
transform O
their O
phenotype O
, O
specifically O
from O
a O
nonfunctional O
NET O
into O
a O
functional O
NET O
, O
and O
from O
one O
functional O
NET O
into O
the O
addition O
of O
another O
functional O
NET O
. O
These O
experiences O
suggest O
that O
the O
presence O
of O
treatment O
- O
resistant O
liver O
metastasis O
might O
be O
a O
hallmark O
of O
the O
potential O
to O
gain O
novel O
functions O
. O
Inherited O
forms O
of O
deafness O
account O
for O
a O
sizable O
portion O
of O
hearing O
loss O
among O
children O
and O
adult O
populations O
. O
Many O
patients O
with O
sensorineural O
deficits O
have O
pathological O
manifestations O
in O
the O
peripheral O
auditory O
system O
, O
the O
inner O
ear O
. O
Within O
the O
hearing O
organ O
, O
the O
cochlea O
, O
most O
of O
the O
genetic O
forms O
of O
hearing O
loss O
involve O
defects O
in O
sensory O
detection O
and O
to O
some O
extent O
, O
signaling O
to O
the O
brain O
via O
the O
auditory O
cranial O
nerve O
. O
This O
review O
focuses O
on O
peripheral O
forms O
of O
hereditary O
hearing O
loss O
and O
how O
these O
impairments O
can O
be O
studied O
in O
diverse O
animal O
models O
or O
patient O
- O
derived O
cells O
with O
the O
ultimate O
goal O
of O
using O
the O
knowledge O
gained O
to O
understand O
the O
underlying O
biology O
and O
treat O
hearing O
loss O
. O
The O
clinical O
presentation O
except O
age O
of O
onset O
is O
similar O
in O
different O
types O
of O
angioedema O
. O
A O
lymphoproliferative O
disorder O
like O
angioimmunoblastic O
T O
cell O
lymphoma O
( O
AITL O
) O
rarely O
presents O
with O
symptoms O
of O
angioedema O
. O
We O
present O
extremely O
rare O
case O
of O
elderly O
male O
with O
recurrent O
tongue O
swelling O
, O
pruritus O
with O
normal O
levels O
of O
complements O
and O
C1 O
esterase O
inhibitor O
protein O
featuring O
as O
acquired O
angioedema O
, O
a O
rare O
manifestation O
of O
AITL O
. O
Initial O
response O
to O
corticosteroids O
may O
be O
misleading O
and O
occurs B-EPI
as O
a O
result O
of O
immunosuppression O
of O
AITL O
. O
High O
index O
of O
suspicion O
may O
prompt O
need O
for O
histopathological O
diagnosis O
of O
lymph O
node O
biopsy O
. O
Definitive O
chemotherapeutic O
treatment O
may O
achieve O
long O
term O
remission O
. O
Objective O
/ O
background O
Knowledge O
of O
idiopathic O
hypersomnia O
symptomatology O
derives O
from O
clinical O
case O
series O
. O
Web O
- O
based O
registries O
provide O
complementary O
information O
by O
allowing O
larger O
sample O
sizes O
, O
with O
greater O
geographic O
and O
social O
diversity O
. O
Patients O
/ O
methods O
Data O
were O
obtained O
from O
the O
Hypersomnia O
Foundation O
's O
online O
registry O
. O
Common O
clinical O
features O
of O
idiopathic O
hypersomnia O
and O
other O
central O
disorders O
of O
hypersomnolence O
were O
queried O
, O
for O
the O
last O
thirty O
days O
and O
when O
symptoms O
were O
most O
severe O
. O
Symptoms O
were O
compared O
between O
idiopathic O
hypersomnia O
participants O
with O
and O
without O
long O
sleep O
durations O
and O
between O
participants O
with O
idiopathic O
hypersomnia O
and O
those O
with O
either O
form O
of O
narcolepsy O
. O
Frequency O
of O
medication O
use O
and O
residual O
symptoms O
on O
medication O
were O
evaluated O
. O
Results O
Five O
- O
hundred O
sixty O
- O
three O
registry O
respondents O
were O
included O
, O
with O
idiopathic O
hypersomnia O
( O
n O
= O
468 O
) O
, O
narcolepsy O
type O
2 O
( O
n O
= O
44 O
) O
, O
and O
narcolepsy O
type O
1 O
( O
n O
= O
51 O
) O
. O
O
Brain O
fog O
, O
O
poor O
memory O
, O
and O
sleep O
drunkenness O
were O
all O
present O
in O
most O
idiopathic O
hypersomnia O
respondents O
, O
with O
brain O
fog O
and O
sleep O
drunkenness O
more O
commonly O
endorsed O
by O
those O
with O
long O
sleep O
durations O
. O
Eighty B-STAT
- O
two O
percent O
of O
participants O
with O
idiopathic O
hypersomnia O
were O
currently O
treated O
with O
medication O
, O
most O
commonly O
traditional O
psychostimulants O
such O
as O
amphetamine O
salts O
. O
Among O
treated O
patients O
, O
symptoms O
improved O
while O
on O
medication O
, O
but O
substantial O
residual O
hypersomnia O
symptoms O
remained O
. O
Participants O
with O
narcolepsy O
type O
1 O
were O
more O
likely O
than O
those O
with O
idiopathic O
hypersomnia O
to O
endorse O
intentional O
and O
unintentional O
daytime O
naps O
and O
automatic O
behaviors O
. O
Conclusions O
Symptoms O
of O
idiopathic O
hypersomnia O
extend O
well O
beyond O
excessive O
daytime O
sleepiness O
, O
and O
these O
symptoms O
frequently O
persist O
despite O
treatment O
. O
These O
findings O
highlight O
the O
importance O
of O
online O
registries O
in O
identifying O
gaps O
in O
the O
use O
and O
effectiveness O
of O
current O
treatments O
. O
The O
Ehlers O
- O
Danlos O
syndromes O
( O
EDS O
) O
are O
a O
group O
of O
13 O
disorders O
, O
clinically O
defined O
through O
features O
of O
joint O
hypermobility O
, O
skin O
hyperextensibility O
, O
and O
tissue O
fragility O
. O
Most O
subtypes O
are O
caused O
by O
mutations O
in O
genes O
affecting O
the O
structure O
or O
processing O
of O
the O
extracellular O
matrix O
( O
ECM O
) O
protein O
collagen O
. O
The O
Hypermobility O
Spectrum O
Disorders O
( O
HSDs O
) O
are O
clinically O
indistinguishable O
disorders O
, O
but O
are O
considered O
to O
lack O
a O
genetic O
basis O
. O
The O
pathogenesis O
of O
all O
these O
disorders O
, O
however O
, O
remains O
poorly O
understood O
. O
Genotype O
- O
phenotype O
correlations O
are O
limited O
, O
and O
findings O
of O
aberrant O
collagen O
fibrils O
are O
inconsistent O
and O
associate O
poorly O
with O
the O
subtype O
and O
severity O
of O
the O
disorder O
. O
The O
defective O
ECM O
, O
however O
, O
also O
has O
consequences O
for O
cellular O
processes O
. O
EDS O
/ O
HSD O
fibroblasts O
exhibit O
a O
dysfunctional O
phenotype O
including O
impairments O
in O
cell O
adhesion O
and O
cytoskeleton O
organization O
, O
though O
the O
pathological O
significance O
of O
this O
has O
remained O
unclear O
. O
Recent O
advances O
in O
our O
understanding O
of O
fibroblast O
mechanobiology O
suggest O
these O
changes O
may O
actually O
reflect O
features O
of O
a O
pathomechanism O
we O
herein O
define O
. O
This O
review O
departs O
from O
the O
traditional O
view O
of O
EDS O
/ O
HSD O
, O
where O
pathogenesis O
is O
mediated O
by O
the O
structurally O
defective O
ECM O
. O
Instead O
, O
we O
propose O
EDS O
/ O
HSD O
may O
be O
a O
disorder O
of O
membrane O
- O
bound O
collagen O
, O
and O
consider O
how O
aberrations O
in O
cell O
adhesion O
and O
cytoskeleton O
dynamics O
could O
drive O
the O
abnormal O
properties O
of O
the O
connective O
tissue O
, O
and O
be O
responsible O
for O
the O
pathogenesis O
of O
EDS O
/ O
HSD O
. O
Recessive O
mutations O
in O
genes O
encoding O
mitochondrial O
DNA O
replication O
machinery O
lead O
to O
mitochondrial O
DNA O
depletion O
syndromes O
. O
This O
genetically O
and O
phenotypically O
heterogeneous O
group O
includes O
infantile O
onset O
spinocerebellar O
ataxia O
( O
OMIM O
# O
271245 O
) O
a O
neurodegenerative O
disease O
caused O
by O
mutations O
in O
the O
mtDNA O
helicase O
gene O
, O
c10orf2 O
, O
with O
an O
increased O
frequency O
in O
the O
Finnish O
population O
due O
to O
a O
founder O
mutation O
. O
We O
describe O
a O
child O
of O
English O
descent O
who O
presented O
with O
a O
severe O
phenotype O
of O
IOSCA O
as O
a O
result O
of O
two O
- O
novel O
mutations O
in O
the O
c10orf2 O
gene O
. O
This O
paper O
expands O
the O
phenotypic O
spectrum O
of O
IOSCA O
and O
adds O
further O
evidence O
for O
the O
presence O
of O
a O
genotype O
- O
phenotype O
correlation O
among O
patients O
with O
recessive O
mutations O
in O
this O
gene O
. O
The O
world O
of O
dermatology O
is O
pieced O
together O
by O
clinical O
conditions O
unique O
in O
their O
colors O
, O
morphology O
, O
and O
configuration O
. O
Dermatological O
signs O
and O
terms O
are O
influenced O
by O
etymology O
, O
language O
, O
and O
history O
. O
Eponyms O
also O
make O
dermatology O
a O
fascinating O
but O
linguistically O
challenging O
subject O
. O
This O
article O
reviews O
dermatological O
conditions O
described O
in O
relation O
to O
fashion O
, O
and O
what O
we O
wear O
in O
everyday O
life O
from O
top O
to O
toe O
, O
demonstrating O
that O
dermatology O
can O
be O
inspired O
even O
in O
the O
most O
common O
things O
. O
Previous O
research O
has O
demonstrated O
a O
high O
prevalence B-EPI
of O
Coxiella O
burnetii O
in O
the O
bulk O
tank O
milk O
on O
large O
industrial O
dairy O
farms O
of O
the O
central O
and O
eastern O
European O
region O
. O
The O
aim O
of O
this O
survey O
was O
to O
estimate O
the O
prevalence B-EPI
of O
specific O
IgG O
antibodies O
to O
C. O
burnetii O
proving O
previous O
infection O
among O
dairy O
farm O
workers O
and O
to O
determine O
the O
possible O
risk O
factors O
. O
Serum O
samples O
from O
veterinarians O
, O
inseminators O
, O
animal O
caretakers O
, O
milking O
parlor O
workers O
, O
and O
herd O
managers O
working O
on O
dairy O
farms O
were O
tested O
for O
the O
presence O
of O
IgG O
to O
phase O
I O
and O
phase O
II O
of O
C. O
burnetii O
using O
an O
indirect O
microimmunofluorescence O
assay O
. O
Antibodies O
phase O
II O
to O
C. O
burnetii O
were O
detected O
in O
59 O
out O
of O
70 O
individuals O
tested O
( O
84.3 O
% O
) O
. O
All O
occupational O
groups O
are O
highly O
exposed O
to O
C. O
burnetii O
infection O
. O
Veterinarians O
, O
inseminators O
, O
and O
animal O
caretakers O
had O
100 O
% O
seropositivity O
rate O
of O
phase O
II O
, O
whereas O
the O
seropositivity O
rate O
found O
among O
herd O
managers O
and O
milking O
parlor O
workers O
was O
71.4 O
% O
and O
47 O
% O
, O
respectively O
. O
The O
findings O
of O
this O
survey O
suggest O
that O
the O
risk O
of O
C. O
burnetii O
infection O
is O
correlated O
with O
cattle O
density O
in O
the O
large O
dairy O
farms O
and O
also O
with O
occupational O
groups O
. O
Craniofacial O
anomalies O
are O
among O
the O
most O
common O
birth O
defects O
and O
are O
associated O
with O
increased O
mortality O
and O
, O
in O
many O
cases O
, O
the O
need O
for O
lifelong O
treatment O
. O
Over O
the O
past O
few O
decades O
, O
dramatic O
advances O
in O
the O
surgical O
and O
medical O
care O
of O
these O
patients O
have O
led O
to O
marked O
improvements O
in O
patient O
outcomes O
. O
However O
, O
none O
of O
the O
treatments O
currently O
in O
clinical O
use O
address O
the O
underlying O
molecular O
causes O
of O
these O
disorders O
. O
Fortunately O
, O
the O
field O
of O
craniofacial O
developmental O
biology O
provides O
a O
strong O
foundation O
for O
improved O
diagnosis O
and O
for O
therapies O
that O
target O
the O
genetic O
causes O
of O
birth O
defects O
. O
In O
this O
chapter O
, O
we O
discuss O
recent O
advances O
in O
our O
understanding O
of O
the O
embryology O
of O
craniofacial O
conditions O
, O
and O
we O
focus O
on O
the O
use O
of O
animal O
models O
to O
guide O
rational O
therapies O
anchored O
in O
genetics O
and O
biochemistry O
. O
Objective O
Classic O
congenital O
adrenal O
hyperplasia O
( O
CAH O
) O
secondary O
to O
21 O
- O
hydroxylase O
deficiency O
is O
characterized O
by O
increased O
prenatal O
adrenal O
androgen O
secretion O
. O
There O
are O
a O
small O
number O
of O
reports O
in O
the O
literature O
showing O
higher O
birth O
weight O
and O
length O
in O
CAH O
newborns O
. O
Methods O
We O
analyzed O
birth O
weight O
and O
length O
data O
of O
116 O
German O
newborns O
( O
48 O
boys O
, O
68 O
girls O
) O
with O
classic O
CAH O
who O
were O
born O
during O
the O
period O
from O
1990 O
to O
2017 O
. O
All O
children O
have O
been O
followed O
or O
are O
currently O
treated O
as O
outpatients O
in O
our O
clinic O
. O
All O
children O
were O
born O
at O
term O
. O
The O
mothers O
were O
healthy O
and O
their O
pregnancies O
were O
uneventful O
. O
The O
diagnosis O
of O
CAH O
was O
confirmed O
by O
molecular O
analyses O
of O
the O
CYP21A2 O
gene O
. O
Birth O
data O
were O
calculated O
as O
standard O
deviation O
( O
SD O
) O
scores O
according O
to O
German O
reference O
values O
. O
Results O
Weight O
and O
length O
in O
male O
CAH O
newborns O
( O
mean O
± O
SD O
) O
( O
3601±576 O
g O
; O
52.4±2.85 O
cm O
) O
were O
significantly O
higher O
than O
in O
female O
CAH O
newborns O
( O
3347±442 O
g O
; O
51.2±2.55 O
cm O
) O
, O
but O
male O
- O
female O
differences O
in O
the O
CAH O
cohort O
were O
lost O
when O
the O
data O
were O
converted O
into O
SD O
scores O
. O
The O
birth O
sizes O
of O
the O
CAH O
newborns O
did O
not O
differ O
from O
the O
reference O
group O
. O
The O
birth O
sizes O
also O
did O
not O
differ O
between O
the O
different O
CAH O
genotypes O
. O
Maternal O
age O
, O
mode O
of O
delivery O
and O
maternal O
parity O
had O
no O
influence O
on O
birth O
size O
. O
Conclusion O
Our O
data O
show O
that O
prenatal O
hyperandrogenism O
does O
not O
affect O
fetal O
growth O
. O
Clinical O
disorders O
known O
to O
affect O
inherited O
gamma O
- O
amino O
butyric O
acid O
( O
GABA O
) O
metabolism O
are O
autosomal O
recessively O
inherited O
succinic O
semialdehyde O
dehydrogenase O
and O
GABA O
- O
transaminase O
deficiency O
. O
The O
clinical O
presentation O
of O
succinic O
semialdehyde O
dehydrogenase O
deficiency O
includes O
intellectual O
disability O
, O
ataxia O
, O
obsessive O
- O
compulsive O
disorder O
and O
epilepsy O
with O
a O
nonprogressive O
course O
in O
typical O
cases O
, O
although O
a O
progressive O
form O
in O
early O
childhood O
as O
well O
as O
deterioration O
in O
adulthood O
with O
worsening O
epilepsy O
are O
reported O
. O
GABA O
- O
transaminase O
deficiency O
is O
associated O
with O
a O
severe O
neonatal O
- O
infantile O
epileptic O
encephalopathy O
. O
Purpose O
To O
describe O
the O
molecular O
epidemiology O
of O
nonsyndromic O
retinitis O
pigmentosa O
( O
RP O
) O
and O
Usher O
syndrome O
( O
US B-LOC
) O
in O
Italian O
patients O
. O
Methods O
A O
total O
of O
591 O
probands O
( O
315 O
with O
family O
history O
and O
276 O
sporadics O
) O
were O
analyzed O
. O
For O
155 O
of O
them O
, O
we O
performed O
a O
family O
segregation O
study O
, O
considering O
a O
total O
of O
382 O
relatives O
. O
Probands O
were O
analyzed O
by O
a O
customized O
multigene O
panel O
approach O
. O
Sanger O
sequencing O
was O
used O
to O
validate O
all O
genetic O
variants O
and O
to O
perform O
family O
segregation O
studies O
. O
Copy O
number O
variants O
of O
selected O
genes O
were O
analyzed O
by O
multiplex O
ligation O
- O
dependent O
probe O
amplification O
. O
Four O
patients O
who O
tested O
negative O
to O
targeted O
next O
- O
generation O
sequencing O
analysis O
underwent O
clinical O
exome O
sequencing O
. O
Results O
The O
mean O
diagnostic O
yield O
of O
molecular O
testing O
among O
patients O
with O
a O
family O
history O
of O
retinal O
disorders O
was O
55.2 O
% O
while O
the O
diagnostic O
yield O
including O
sporadic O
cases O
was O
37.4 B-STAT
% I-STAT
. O
We O
found O
468 O
potentially O
pathogenic O
variants O
, O
147 O
of O
which O
were O
unpublished O
, O
in O
308 O
probands O
and O
66 O
relatives O
. O
Mean O
ages O
of O
onset O
of O
the O
different O
classes O
of O
RP O
were O
autosomal O
dominant O
RP O
, O
19.3 O
± O
12.6 O
years O
; O
autosomal O
recessive O
RP O
, O
23.2 O
± O
16.6 O
years O
; O
X O
- O
linked O
RP O
, O
13.9 O
± O
9.9 O
years O
; O
and O
Usher O
syndrome O
, O
18.9 O
± O
9.5 O
years O
. O
We O
reported O
potential O
new O
genotype O
- O
phenotype O
correlations O
in O
three O
probands O
, O
two O
revealed O
by O
TruSight O
One O
testing O
. O
All O
three O
probands O
showed O
isolated O
RP O
caused O
by O
biallelic O
variants O
in O
genes O
usually O
associated O
with O
syndromes O
such O
as O
PERCHING O
and O
Senior O
- O
Loken O
or O
with O
retinal O
dystrophy O
, O
iris O
coloboma O
, O
and O
comedogenic O
acne O
syndrome O
. O
Conclusions O
This O
is O
the O
largest O
molecular O
study O
of O
Italian O
patients O
with O
RP O
in O
the O
literature O
, O
thus O
reflecting O
the O
epidemiology O
of O
the O
disease O
in O
Italy B-LOC
with O
reasonable O
accuracy O
. O
Nontuberculous O
mycobacterial O
( O
NTM O
) O
infections O
in O
humans O
have O
increased O
in O
prevalence B-EPI
in O
recent O
decades O
. O
Mycobacterium O
kansasii O
is O
one O
of O
the O
most O
prevalent B-EPI
human O
pathogenic O
NTM O
species O
worldwide B-LOC
. O
Herein O
, O
we O
report O
the O
first O
isolation O
of O
M. O
kansasii O
from O
an O
indoor O
domestic O
cat O
in O
Japan B-LOC
. O
Comparative O
genome O
sequence O
analysis O
of O
the O
feline O
isolate O
showed O
this O
pathogen O
is O
genetically O
identical O
to O
human O
pathogenic O
M. O
kansasii O
. O
This O
finding O
suggests O
that O
M. O
kansasii O
has O
a O
potential O
risk O
of O
zoonoses O
and O
requires O
the O
O
One O
Health O
O
approach O
to O
control O
NTM O
infection O
. O
Hearing O
loss O
is O
highly O
prevalent B-EPI
and O
may O
significantly O
affect O
how O
we O
age O
. O
Although O
the O
population O
is O
aging O
, O
relatively O
few O
adults O
receive O
treatment O
for O
hearing O
loss O
. O
Internists O
are O
a O
critical O
partner O
to O
audiologists O
and O
otolaryngologists O
in O
caring O
for O
the O
adult O
population O
with O
hearing O
loss O
. O
This O
review O
provides O
a O
primer O
on O
diagnosing O
and O
managing O
hearing O
loss O
. O
Q O
fever O
can O
present O
as O
a O
fever O
of O
unknown O
aetiology O
and O
can O
be O
challenging O
to O
diagnose O
because O
of O
the O
rare O
incidence B-EPI
. O
It O
can O
present O
as O
an O
acute O
illness O
with O
manifestations O
, O
including O
influenza O
- O
like O
symptoms O
, O
hepatitis O
, O
pneumonia O
or O
chronic O
disease O
involving O
the O
cardiovascular O
system O
. O
We O
present O
a O
case O
of O
a O
39 O
- O
year O
- O
old O
woman O
in O
the O
USA B-LOC
, O
who O
developed O
acute O
Q O
fever O
with O
associated O
sepsis O
and O
severe O
hepatitis O
. O
She O
received O
treatment O
with O
recovery O
from O
acute O
infection O
but O
currently O
has O
symptoms O
of O
post O
Q O
fever O
syndrome O
. O
Background O
Approximately O
70 O
% O
of O
congenital O
deafness O
is O
attributable O
to O
genetic O
causes O
. O
Incidence B-EPI
of O
congenital O
deafness O
is O
known O
to O
be O
higher O
in O
families O
with O
consanguineous O
marriage O
. O
In O
this O
study O
, O
we O
investigated O
the O
genetic O
causes O
in O
three O
consanguineous O
Pakistani O
families O
segregating O
with O
prelingual O
, O
severe O
- O
to O
- O
profound O
deafness O
. O
Results O
Through O
targeted O
next O
- O
generation O
sequencing O
of O
414 O
genes O
known O
to O
be O
associated O
with O
deafness O
, O
homozygous O
variants O
c.536del O
( O
p. O
Leu180Serfs∗20 O
) O
in O
TECTA O
, O
c.3719 O
G O
> O
A O
( O
p. O
Arg1240Gln O
) O
in O
MYO7A B-LOC
, O
and O
c.482 O
+ O
1986_1988del O
in O
HGF O
were O
identified O
as O
the O
pathogenic O
causes O
of O
enrolled O
families O
. O
Interestingly O
, O
in O
one O
large O
consanguineous O
family O
, O
an O
additional O
c.706G O
> O
A O
( O
p. O
Glu236Lys O
) O
variant O
in O
the O
X O
- O
linked O
POU3F4 O
gene O
was O
also O
identified O
in O
multiple O
affected O
family O
members O
causing O
deafness O
. O
Genotype O
- O
phenotype O
cosegregation O
was O
confirmed O
in O
all O
participating O
family O
members O
by O
Sanger O
sequencing O
. O
Conclusions O
Our O
results O
showed O
that O
the O
genetic O
causes O
of O
deafness O
are O
highly O
heterogeneous O
. O
Even O
within O
a O
single O
family O
, O
the O
affected O
members O
with O
apparently O
indistinguishable O
clinical O
phenotypes O
may O
have O
different O
pathogenic O
variants O
. O
Diseases O
of O
the O
retina O
are O
major O
causes O
of O
visual O
impairment O
and O
blindness O
in O
developed O
countries O
and O
, O
due O
to O
an O
ageing O
population O
, O
their O
prevalence B-EPI
is O
continually O
rising O
. O
The O
lack O
of O
effective O
therapies O
and O
the O
limitations O
of O
those O
currently O
in O
use O
highlight O
the O
importance O
of O
continued O
research O
into O
the O
pathogenesis O
of O
these O
diseases O
. O
Vascular O
endothelial O
growth O
factor O
( O
VEGF O
) O
plays O
a O
major O
role O
in O
driving O
vascular O
dysfunction O
in O
retinal O
disease O
and O
has O
therefore O
become O
a O
key O
therapeutic O
target O
. O
Recent O
evidence O
also O
points O
to O
a O
potentially O
similarly O
important O
role O
of O
galectins O
, O
a O
family O
of O
β O
- O
galactoside O
- O
binding O
proteins O
. O
Indeed O
, O
they O
have O
been O
implicated O
in O
regulating O
fundamental O
processes O
, O
including O
vascular O
hyperpermeability O
, O
angiogenesis O
, O
neuroinflammation O
, O
and O
oxidative O
stress O
, O
all O
of O
which O
also O
play O
a O
prominent O
role O
in O
retinopathies O
. O
Here O
, O
we O
review O
direct O
evidence O
for O
pathological O
roles O
of O
galectins O
in O
retinal O
disease O
. O
In O
addition O
, O
we O
extrapolate O
potential O
roles O
of O
galectins O
in O
the O
retina O
from O
evidence O
in O
cancer O
, O
immune O
and O
neuro O
- O
biology O
. O
We O
conclude O
that O
there O
is O
value O
in O
increasing O
understanding O
of O
galectin O
function O
in O
retinal O
biology O
, O
in O
particular O
in O
the O
context O
of O
the O
retinal O
vasculature O
and O
microglia O
. O
With O
greater O
insight O
, O
recent O
clinical O
developments O
of O
galectin O
- O
targeting O
drugs O
could O
potentially O
also O
be O
of O
benefit O
to O
the O
clinical O
management O
of O
many O
blinding O
diseases O
. O
Introduction O
Classic O
bladder O
exstrophy O
( O
BE O
) O
is O
regarded O
as O
an O
isolated O
malformation O
without O
any O
further O
anomalies O
, O
but O
some O
studies O
have O
indicated O
a O
higher O
incidence B-EPI
of O
cardiac O
anomalies O
. O
This O
cross O
- O
sectional O
study O
is O
planned O
to O
evaluate O
the O
prevalence B-EPI
of O
congenital O
heart O
defects O
( O
CHDs O
) O
and O
the O
clinical O
relevance O
for O
patients O
with O
BE O
admitted O
for O
primary O
closure O
. O
Materials O
and O
methods O
Patients O
were O
prospectively O
recruited O
between O
March O
2012 O
and O
January O
2019 O
. O
Patients O
' O
profiles O
including O
demographic O
data O
, O
results O
of O
transthoracic O
echocardiography O
( O
TTE O
) O
, O
as O
well O
as O
essential O
peri- O
and O
postoperative O
data O
were O
assessed O
. O
Results O
Thirty O
- O
nine O
( O
25 O
boys O
and O
14 O
girls O
) O
patients O
with O
BE O
( O
median O
age O
61 O
days O
) O
underwent O
delayed O
primary O
bladder O
closure O
. O
Thirty O
- O
seven O
( O
24 O
boys O
and O
13 O
girls O
) O
patients O
had O
received O
TTE O
1 O
day O
before O
surgery O
. O
CHD O
was O
detected O
in O
7 B-STAT
( O
18.9 O
% O
) O
out O
of O
the O
39 O
patients O
, O
but O
no O
clinical O
differences O
between O
patients O
with O
and O
without O
CHD O
were O
observed O
peri- O
or O
postoperatively O
. O
Discussion O
and O
conclusion O
This O
prospective O
systematic O
evaluation O
shows O
an O
even O
higher O
rate O
of O
CHD O
in O
patients O
with O
BE O
than O
assumed O
previously O
. O
Although O
peri- O
and O
postoperative O
outcome O
did O
not O
differ O
between O
patients O
with O
and O
without O
CHD O
, O
we O
consider O
TTE O
an O
important O
additional O
method O
for O
ensuring O
a O
safe O
peri- O
and O
postoperative O
courses O
and O
a O
short- O
and O
long O
- O
term O
care O
for O
patients O
with O
CHD O
. O
Oculomotor O
abnormalities O
are O
common O
in O
the O
spinocerebellar O
ataxias O
( O
SCAs O
) O
. O
In O
studies O
of O
SCAs O
1 B-STAT
, I-STAT
2 I-STAT
, O
3 O
, O
and O
6 O
, O
eye O
movement O
abnormalities O
correlate O
with O
disease O
severity O
. O
Oculomotor O
abnormalities O
may O
be O
the O
sole O
motor O
manifestation O
of O
early O
and/or O
premanifest O
disease O
; O
however O
, O
not O
all O
ataxia O
rating O
scales O
include O
oculomotor O
assessment O
. O
We O
sought O
to O
identify O
the O
prevalence B-EPI
and O
characteristics O
of O
oculomotor O
abnormalities O
at O
first O
presentation O
in O
a O
large O
SCA O
cohort O
, O
including O
those O
in O
earlier O
stages O
of O
disease O
. O
We O
performed O
a O
retrospective O
assessment O
of O
initial O
clinical O
examinations O
of O
SCA O
patients O
followed O
in O
the O
Massachusetts O
General O
Hospital O
Ataxia O
Unit O
and O
assessed O
with O
the O
Brief O
Ataxia O
Rating O
Scale O
( O
BARS O
) O
. O
One O
hundred O
thirty O
- O
four O
SCA O
patients O
were O
assessed O
: O
17 O
SCA1 O
, O
13 O
SCA2 O
, O
55 O
SCA3 O
, O
2 O
SCA5 O
, O
22 O
SCA6 O
, O
11 O
SCA7 O
, O
9 O
SCA8 O
, O
and O
5 O
SCA17 O
, O
mainly O
in O
the O
early O
stages O
of O
disease O
( O
67.2 O
% O
stage O
0 O
- O
1 O
) O
. O
Oculomotor O
abnormalities O
were O
present O
on O
initial O
assessment O
in O
94.8 O
% O
, O
including O
7/9 B-STAT
stage O
0 B-STAT
and I-STAT
77/81 I-STAT
stage O
1 O
patients O
. O
Stage O
0/1 B-STAT
patients O
had O
frequent O
saccadic O
intrusions O
, O
nystagmus O
, O
and O
hypo O
/ O
hypermetric O
saccades O
. O
Saccadic O
slowing O
was O
present O
even O
in O
early O
stage O
SCA7 O
and O
SCA2 O
, O
eventually O
leading O
to O
ophthalmoplegia O
. O
The O
burden O
of O
oculomotor O
abnormalities O
correlated O
with O
disease O
stage O
, O
duration O
, O
and O
severity O
, O
remaining O
highly O
significant O
even O
when O
controlling O
for O
age O
. O
The O
ubiquitous O
presence O
of O
oculomotor O
abnormalities O
in O
the O
SCAs O
, O
particularly O
early O
in O
the O
course O
, O
underscores O
the O
importance O
of O
oculomotor O
assessment O
in O
ataxia O
rating O
scales O
such O
as O
BARS O
. O
These O
findings O
highlight O
the O
potential O
for O
quantitative O
physiological O
oculomotor O
measures O
as O
clinical O
biomarkers O
in O
natural O
history O
studies O
and O
clinical O
trials O
. O
Carbimazole O
( O
CMZ O
) O
and O
its O
active O
metabolite O
methimazole O
( O
MMI O
) O
are O
antithyroid O
medications O
, O
which O
can O
result O
in O
MMI O
/ O
CMZ O
embryopathy O
in O
susceptible O
individuals O
. O
The O
incidence B-EPI
of O
birth O
defects O
related O
to O
MMI O
/ O
CMZ O
embryopathy O
remains O
unclear O
as O
several O
epidemiologic O
studies O
failed O
to O
prove O
a O
correlation O
, O
despite O
positive O
case O
- O
control O
studies O
and O
numerous O
case O
reports O
. O
Malformations O
reported O
in O
exposed O
individuals O
and O
commonly O
recognized O
as O
MMI O
/ O
CMZ O
embryopathy O
include O
cutis O
aplasia O
of O
the O
scalp O
, O
choanal O
atresia O
, O
esophageal O
atresia O
( O
EA O
) O
, O
tracheo O
- O
esophageal O
fistula O
( O
TEF O
) O
, O
persistent O
vitelline O
duct O
, O
athelia O
/ O
hypothelia O
, O
and O
subtle O
facial O
dysmorphisms O
including O
sparse O
or O
arched O
eyebrows O
. O
Here O
, O
we O
report O
on O
individuals O
with O
early O
pregnancy O
exposure O
to O
MMI O
, O
with O
microtia O
and O
various O
other O
anomalies O
associated O
with O
MMI O
embryopathy O
, O
suggesting O
that O
microtia O
is O
also O
seen O
with O
increased O
frequency O
after O
prenatal O
MMI O
exposure O
. O
Additional O
unusual O
malformations O
among O
our O
patients O
include O
a O
previously O
unreported O
type O
of O
TEF O
with O
three O
separate O
esophageal O
pouches O
and O
a O
fistula O
connecting O
the O
middle O
pouch O
to O
the O
trachea O
in O
one O
child O
, O
and O
absence O
of O
the O
gall O
bladder O
in O
another O
. O
An O
enlarged O
anterior O
fontanel O
was O
seen O
in O
three O
patients O
, O
and O
clinodactyly O
of O
the O
fifth O
finger O
was O
noted O
in O
three O
. O
The O
similarities O
between O
our O
three O
patients O
with O
microtia O
after O
MMI O
exposure O
and O
the O
two O
previously O
reported O
with O
microtia O
after O
CMZ O
exposure O
support O
the O
concept O
of O
microtia O
being O
related O
to O
the O
MMI O
/ O
CMZ O
exposure O
. O
Recognition O
of O
microtia O
as O
a O
manifestation O
of O
MMI O
/ O
CMZ O
embryopathy O
will O
likely O
increase O
the O
number O
of O
diagnosed O
cases O
and O
thus O
affect O
ascertainment O
. O
We O
propose O
diagnostic O
criteria O
for O
MMI O
/ O
CMZ O
embryopathy O
, O
including O
the O
presence O
of O
at O
least O
one O
major O
characteristic O
finding O
. O
Distal O
renal O
tubular O
acidosis O
( O
dRTA O
) O
, O
or O
RTA O
type O
1 O
, O
a O
rare O
inherited O
or O
acquired O
disease O
, O
is O
a O
disorder O
of O
the O
distal O
tubule O
caused O
by O
impaired O
urinary O
acid O
secretion O
. O
Due O
to O
associated O
conditions O
and O
nonspecific O
symptoms O
, O
dRTA O
may O
go O
undetected O
. O
This O
analysis O
aims O
to O
estimate O
the O
prevalence B-EPI
of O
dRTA O
in O
the O
UK O
Clinical O
Practice O
Research O
Datalink O
( O
CPRD O
) O
databases O
and O
extrapolate O
it O
to O
European O
Union O
Five O
( O
EU5 O
) O
populations O
. O
A O
retrospective O
analysis O
was O
conducted O
using O
the O
CPRD O
GOLD O
database O
and O
linked O
Hospital O
Episode O
Statistics O
( O
HES O
) O
data O
to O
identify O
diagnosed O
and O
potentially O
undiagnosed O
or O
miscoded O
patients O
( O
suspected O
patients O
) O
. O
Patients O
' O
records O
with O
at O
least O
one O
diagnosis O
code O
for O
dRTA O
, O
RTA O
, O
specific O
autoimmune O
diseases O
, O
or O
renal O
disorders O
recorded O
between O
January O
1987 O
and O
November O
2017 O
were O
obtained O
and O
analyzed O
. O
An O
algorithm O
was O
developed O
to O
detect O
potentially O
undiagnosed O
/ O
miscoded O
dRTA O
, O
based O
on O
associated O
conditions O
and O
prescriptions O
. O
A O
total O
of O
216 O
patients O
with O
diagnosis O
of O
RTA O
or O
dRTA O
were O
identified O
( O
with O
98 O
linked O
to O
hospital O
data O
) O
, O
and O
447 O
patients O
were O
identified O
as O
having O
suspected O
dRTA O
. O
dRTA O
prevalence B-EPI
for O
2017 O
was O
estimated O
between O
0.46 O
( O
recorded O
cases O
, O
of O
which O
22.1 O
% O
were O
considered O
primary O
) O
and O
1.60 O
when O
including O
suspected O
cases O
( O
7.6 O
% O
primary O
) O
per I-STAT
10,000 I-STAT
people I-STAT
. O
Prescription O
and O
clinical O
records O
of O
diagnosed O
patients O
revealed O
a O
wide O
range O
of O
comorbidities O
and O
a O
need O
for O
pharmacological O
treatment O
to O
manage O
associated O
symptoms O
. O
The O
study O
provides O
new O
estimates O
of O
dRTA O
prevalence B-EPI
in O
Europe B-LOC
and O
suggests O
that O
patients O
may O
often O
be O
unreported O
or O
miscoded O
, O
potentially O
confounding O
appropriate O
disease O
management O
. O
It O
has O
been O
well O
- O
established O
that O
cancer O
cells O
are O
under O
constant O
oxidative O
stress O
, O
as O
reflected O
by O
elevated O
basal O
level O
of O
reactive O
oxygen O
species O
( O
ROS O
) O
, O
due O
to O
increased O
metabolism O
driven O
by O
aberrant O
cell O
growth O
. O
Cancer O
cells O
can O
adapt O
to O
maintain O
redox O
homeostasis O
through O
a O
variety O
of O
mechanisms O
. O
The O
prevalent B-EPI
perception O
about O
ROS O
is O
that O
they O
are O
one O
of O
the O
key O
drivers O
promoting O
tumor O
initiation O
, O
progression O
, O
metastasis O
, O
and O
drug O
resistance O
. O
Based O
on O
this O
notion O
, O
numerous O
antioxidants O
that O
aim O
to O
mitigate O
tumor O
oxidative O
stress O
have O
been O
tested O
for O
cancer O
prevention O
or O
treatment O
, O
although O
the O
effectiveness O
of O
this O
strategy O
has O
yet O
to O
be O
established O
. O
In O
recent O
years O
, O
it O
has O
been O
increasingly O
appreciated O
that O
ROS O
have O
a O
complex O
, O
multifaceted O
role O
in O
the O
tumor O
microenvironment O
( O
TME O
) O
, O
and O
that O
tumor O
redox O
can O
be O
targeted O
to O
amplify O
oxidative O
stress O
inside O
the O
tumor O
to O
cause O
tumor O
destruction O
. O
Accumulating O
evidence O
indicates O
that O
cancer O
immunotherapies O
can O
alter O
tumor O
redox O
to O
intensify O
tumor O
oxidative O
stress O
, O
resulting O
in O
ROS O
- O
dependent O
tumor O
rejection O
. O
Herein O
we O
review O
the O
recent O
progresses O
regarding O
the O
impact O
of O
ROS O
on O
cancer O
cells O
and O
various O
immune O
cells O
in O
the O
TME O
, O
and O
discuss O
the O
emerging O
ROS O
- O
modulating O
strategies O
that O
can O
be O
used O
in O
combination O
with O
cancer O
immunotherapies O
to O
achieve O
enhanced O
antitumor O
effects O
. O
The O
recent O
discovery O
of O
genes O
involved O
in O
familial O
forms O
of O
nephrotic O
syndrome O
represents O
a O
break O
- O
through O
in O
nephrology O
. O
To O
date O
, O
15 O
genes O
have O
been O
characterized O
and O
several O
new O
loci O
have O
been O
identified O
, O
with O
a O
potential O
for O
discovery O
of O
new O
genes O
. O
Overall O
, O
these O
genes O
account O
for O
a O
large O
fraction O
of O
familial O
forms O
of O
nephrotic O
syndrome O
, O
but O
they O
can O
also O
be O
recognized O
in O
10 B-STAT
- O
20 O
% O
of O
sporadic O
cases O
. O
These O
advances O
increase O
diagnostic O
and O
therapeutic O
potentials O
, O
but O
also O
add O
higher O
complexity O
to O
the O
scenario O
, O
requiring O
clear O
definitions O
of O
clinical O
, O
histopathological O
and O
molecular O
signatures O
. O
In O
general O
, O
genetic O
forms O
of O
nephrotic O
syndrome O
are O
resistant O
to O
common O
therapeutic O
approaches O
( O
that O
include O
steroids O
and O
calcineurin O
inhibitors O
) O
but O
, O
in O
a O
few O
cases O
, O
drug O
response O
or O
spontaneous O
remission O
suggest O
a O
complex O
pathogenesis O
. O
Finally O
, O
syndromic O
variants O
can O
be O
recognized O
on O
the O
basis O
of O
the O
associated O
extra O
- O
renal O
manifestations O
. O
In O
this O
educational O
review O
, O
clinical O
, O
histological O
and O
molecular O
aspects O
of O
various O
forms O
of O
familial O
nephrotic O
syndrome O
have O
been O
reviewed O
in O
an O
attempt O
to O
define O
a O
rational O
diagnostic O
approach O
. O
The O
proposed O
model O
focuses O
on O
practical O
and O
economic O
issues O
, O
taking O
into O
consideration O
the O
impossibility O
of O
using O
genetic O
testing O
as O
starting O
diagnostic O
tool O
. O
The O
final O
objective O
of O
this O
review O
is O
to O
outline O
a O
diagnostic O
flow O
- O
chart O
for O
clinicians O
and O
geneticists O
and O
to O
generate O
a O
rational O
scheme O
for O
molecular O
testing O
. O
Pyridoxine O
- O
dependent O
epilepsy O
( O
PDE O
) O
is O
a O
recessive O
genetic O
disease O
characterized O
by O
epileptic O
encephalopathy O
with O
therapeutic O
response O
to O
pharmacological O
doses O
of O
pyridoxine O
and O
resistance O
to O
anti O
- O
epileptic O
treatments O
. O
The O
recent O
discovery O
in O
2006 O
of O
the O
genetic O
defect O
antiquitin O
( O
ALDH7A1 O
, O
OMIM O
# O
266100 O
) O
has O
helped O
to O
understand O
the O
underlying O
mechanism O
, O
which O
is O
the O
accumulation O
of O
neurotoxic O
intermediates O
in O
the O
lysine O
catabolic O
pathway O
. O
The O
goal O
of O
the O
new O
therapeutic O
approach O
, O
termed O
triple O
therapy O
( O
TT O
) O
( O
pyridoxine O
, O
lysine O
- O
restricted O
diet O
and O
arginine O
supplementation O
) O
, O
is O
to O
improve O
epilepsy O
control O
and O
neurocognitive O
development O
in O
patients O
with O
PDE O
. O
We O
present O
the O
3 O
- O
year O
treatment O
outcome O
for O
a O
child O
with O
PDE O
on O
pyridoxine O
treatment O
( O
started O
at O
age O
5 O
months O
) O
, O
lysine O
- O
restricted O
diet O
( O
started O
at O
age O
17 O
months O
) O
and O
arginine O
supplementation O
therapy O
( O
started O
at O
age O
19 O
months O
) O
. O
The O
TT O
was O
well O
- O
tolerated O
with O
good O
compliance O
. O
No O
adverse O
events O
were O
reported O
. O
We O
observed O
a O
neurodevelopmental O
improvement O
, O
significantly O
fewer O
seizures O
, O
and O
a O
reduction O
of O
pipecolic O
acid O
( O
PA O
) O
as O
a O
biomarker O
of O
the O
illness O
. O
Our O
results O
show O
an O
improving O
clinical O
evolution O
, O
supporting O
and O
extending O
previous O
studies O
reporting O
efficacy O
of O
TT O
. O
Objectives O
To O
review O
the O
data O
of O
infants O
and O
children O
with O
suspected O
monogenic O
diabetes O
who O
underwent O
genetic O
testing O
. O
Methods O
Monogenic O
diabetes O
is O
a O
rare O
form O
of O
diabetes O
resulting O
from O
mutations O
in O
a O
single O
gene O
. O
It O
can O
be O
caused O
by O
dominant O
as O
well O
as O
recessive O
modes O
of O
inheritance O
. O
In O
a O
country O
like O
Pakistan B-LOC
where O
interfamily O
marriages O
are O
common O
the O
incidence B-EPI
of O
genetic O
disorders O
is O
increased O
. O
As O
Pakistan B-LOC
a O
resource O
- O
poor O
country O
, O
the O
diagnosis O
of O
insulin O
- O
dependent O
diabetes O
is O
often O
delayed O
and O
a O
genetic O
diagnosis O
of O
monogenic O
diabetes O
is O
extremely O
difficult O
. O
Children O
with O
clinical O
diagnosis O
of O
monogenic O
and O
syndromic O
diabates O
were O
recruited O
and O
blood O
samples O
were O
sent O
for O
genetic O
analysis O
. O
Results O
One O
thousand O
sixty O
four O
new O
cases O
diagnosed O
with O
type O
1 O
diabetes O
were O
registered O
at O
the O
National O
Institute O
of O
Child O
Health O
, O
Karachi B-LOC
, O
in O
the O
last O
10 O
years O
. O
Of O
these O
39 O
patients O
were O
selected O
for O
genetic O
testing O
who O
were O
diagnosed O
with O
diabetes O
/ O
had O
a O
sibling O
diagnosed O
with O
diabetes O
before O
the O
age O
of O
nine O
months O
( O
n O
= O
27 O
) O
or O
had O
extra O
pancreatic O
features O
( O
n= O
12 O
) O
. O
We O
identified O
mutations O
in O
18/27 B-STAT
cases O
diagnosed O
with O
diabetes O
before O
nine O
months O
of O
age O
. O
The O
most O
common O
genetic O
subtype O
was O
WolcottRallison O
syndrome O
caused O
by O
EIF2AK3 O
mutations O
( O
seven O
cases O
) O
. O
KCNJ11 O
mutations O
were O
identified O
in O
two O
cases O
, O
ABCC8 O
mutations O
were O
identified O
in O
four O
cases O
from O
three O
families O
, O
GCK O
and O
INS O
mutations O
were O
each O
identified O
in O
two O
cases O
, O
and O
one O
SLC2A2 O
mutation O
was O
identified O
in O
one O
case O
. O
A O
genetic O
diagnosis O
was O
made O
in O
12/12 B-STAT
children O
from O
six O
families O
with O
diabetes O
diagnosed O
after O
the O
age O
of O
nine O
months O
who O
had O
extrapancreatic O
features O
. O
Six O
patients O
had O
genetically O
confirmed O
Wolfram O
syndrome O
( O
WFS1 O
) O
, O
three O
had O
thiamine O
- O
responsive O
megaloblastic O
anemia O
( O
SLC19A2 O
) O
and O
three O
were O
diagnosed O
with O
histocytosis O
lymphadenopathy O
plus O
syndrome O
( O
SLC29A3 O
) O
. O
Conclusions O
Genetic O
testing O
is O
essential O
to O
confirm O
a O
diagnosis O
of O
monogenic O
diabetes O
which O
guides O
clinical O
management O
and O
future O
counselling O
. O
Our O
study O
highlights O
the O
importance O
of O
diagnosing O
monogenic O
diabetes O
in O
the O
largely O
consanguineously O
- O
married O
population O
of O
Pakistan B-LOC
. O
Frontal O
fibrosing O
alopecia O
( O
FFA O
) O
is O
a O
variant O
of O
lichen O
planopilaris O
( O
LPP O
) O
with O
characteristic O
band O
- O
like O
frontotemporal O
hairline O
involvement O
and O
eyebrow O
loss O
. O
It O
most O
commonly O
occurs B-EPI
in O
post O
- O
menopausal O
White O
women O
. O
1 O
In O
skin O
of O
color O
( O
SOC O
) O
individuals O
, O
FFA O
is O
often O
misdiagnosed O
as O
traction O
alopecia O
( O
TA O
) O
, O
2 O
and O
little O
data O
exists O
regarding O
the O
presentation O
of O
FFA O
in O
the O
SOC O
patient O
population O
. O
3 O
As O
FFA O
incidence B-EPI
continues O
to O
increase O
, O
4 O
we O
aim O
to O
understand O
differences O
in O
the O
presentation O
of O
FFA O
between O
White O
and O
Black O
women O
in O
order O
to O
aid O
in O
the O
accurate O
and O
timely O
diagnosis O
as O
well O
as O
help O
inform O
prognosis O
and O
management O
. O
Unilateral O
lung O
agenesis O
is O
a O
relatively O
rare O
congenital O
anomaly O
with O
a O
reported O
incidence B-EPI
of O
1 B-STAT
in I-STAT
15 I-STAT
000 I-STAT
births I-STAT
. O
It O
is O
frequently O
associated O
with O
other O
congenital O
malformations O
. O
Some O
of O
the O
sequelae O
of O
lung O
agenesis O
are O
potentially O
life O
- O
threatening O
. O
Here O
, O
we O
report O
a O
case O
of O
left O
lung O
agenesis O
in O
association O
with O
hiatal O
hernia O
and O
atrioventricular O
septal O
defect O
, O
a O
rare O
combination O
of O
anomalies O
which O
have O
not O
been O
described O
previously O
in O
the O
literature O
. O
Li O
- O
Fraumeni O
syndrome O
( O
LFS O
) O
is O
a O
hereditary O
cancer O
predisposition O
syndrome O
, O
with O
the O
characteristics O
of O
early O
onset O
of O
cancer O
and O
high O
cancer O
incidence B-EPI
. O
TP53 O
is O
widely O
accepted O
as O
a O
pathogenic O
gene O
of O
LFS O
. O
A O
2 O
years O
and O
6 O
months O
old O
boy O
is O
reported O
in O
this O
article O
, O
who O
was O
diagnosed O
with O
embryonal O
rhabdomyosarcoma O
( O
RMS O
) O
in O
the O
left O
submandibular O
region O
. O
His O
brother O
died O
of O
RMS O
, O
and O
his O
grandmother O
was O
diagnosed O
with O
breast O
cancer O
. O
TP53 O
gene O
mutation O
detection O
was O
performed O
in O
this O
patient O
and O
some O
family O
members O
, O
indicating O
a O
missense O
mutation O
in O
exon O
8 O
of O
the O
patient O
: O
c.844C O
> O
T O
( O
p. O
Arg282Trp O
, O
heterozygous O
) O
. O
TP53 O
mutation O
was O
also O
found O
in O
his O
mother O
and O
sister O
. O
The O
boy O
met O
the O
diagnostic O
criteria O
for O
LFS O
. O
Among O
pediatric O
patients O
, O
the O
most O
common O
LFS O
diseases O
include O
osteosarcoma O
, O
adrenocortical O
cancer O
, O
central O
nervous O
system O
tumor O
, O
and O
soft O
tissue O
tumor O
. O
Additionally O
, O
leukemia O
and O
lymphoma O
are O
also O
involved O
. O
LFS O
patients O
have O
a O
high O
risk O
to O
suffer O
secondary O
or O
even O
multiple O
cancers O
. O
Therefore O
, O
it O
is O
necessary O
to O
perform O
genetic O
detection O
for O
pediatric O
cancer O
patients O
, O
especially O
those O
with O
hereditary O
predisposition O
cancers O
. O
TP53 O
mutation O
often O
indicates O
poor O
prognosis O
, O
so O
it O
is O
important O
to O
take O
active O
treatment O
and O
systematic O
monitoring O
for O
LFS O
family O
. O
The O
escalating O
prevalence B-EPI
of O
coronavirus O
disease O
2019 O
( O
COVID-19 O
) O
worldwide B-LOC
, O
with O
an O
increased O
rate O
of O
morbidity O
and O
mortality O
, O
highlights O
an O
urgent O
need O
to O
develop O
more O
effective O
therapeutic O
interventions O
. O
Despite O
the O
authorized O
treatment O
against O
COVID-19 O
by O
the O
European O
Union O
( O
EU O
) O
, O
the O
safety O
and O
effectiveness O
of O
this O
therapeutic O
strategy O
for O
a O
wide O
variety O
of O
patients O
have O
remained O
a O
significant O
challenge O
. O
In O
this O
respect O
, O
micronutrients O
such O
as O
vitamins O
and O
minerals O
, O
as O
essential O
factors O
, O
can O
be O
considered O
for O
improving O
the O
function O
of O
the O
immune O
system O
and O
accelerating O
the O
treatment O
procedure O
. O
Dietary O
supplements O
can O
attenuate O
vascular O
and O
inflammatory O
manifestations O
related O
to O
infectious O
diseases O
in O
large O
part O
due O
to O
their O
anti O
- O
inflammatory O
and O
antioxidant O
properties O
. O
Recently O
, O
it O
has O
been O
revealed O
that O
poor O
nutritional O
status O
may O
be O
one O
of O
the O
notable O
risk O
factors O
in O
severe O
COVID-19 O
infections O
. O
In O
the O
current O
review O
, O
we O
focus O
on O
the O
micronutrient O
therapy O
of O
COVID-19 O
patients O
and O
provide O
a O
comprehensive O
insight O
into O
the O
essential O
vitamins O
/ O
minerals O
and O
their O
role O
in O
controlling O
the O
severity O
of O
the O
COVID-19 O
infection O
. O
We O
also O
discuss O
the O
recent O
advancements O
, O
challenges O
, O
negative O
and O
positive O
outcomes O
in O
relevance O
to O
this O
approach O
. O
The O
Xp22.31 O
segment O
of O
the O
short O
arm O
of O
the O
human O
X O
chromosome O
is O
a O
region O
of O
high O
instability O
with O
frequent O
rearrangement O
. O
The O
duplication O
of O
this O
region O
has O
been O
found O
in O
healthy O
people O
as O
well O
as O
in O
individuals O
with O
varying O
degrees O
of O
neurological O
impairment O
. O
The O
incidence B-EPI
has O
been O
reported O
in O
a O
range O
of O
0.4 B-STAT
- I-STAT
0.44 I-STAT
% I-STAT
of O
the O
patients O
with O
neurological O
impairment O
. O
Moreover O
, O
there O
is O
evidence O
that O
Xp22.31 O
duplication O
may O
cause O
a O
common O
phenotype O
including O
developmental O
delay O
, O
intellectual O
disability O
, O
feeding O
difficulty O
, O
autistic O
spectrum O
disorders O
, O
hypotonia O
, O
seizures O
, O
and O
talipes O
. O
We O
report O
on O
a O
patient O
with O
microcephaly O
and O
trigonocephaly O
, O
moderate O
intellectual O
disability O
, O
speech O
and O
language O
delay O
, O
and O
poor O
social O
interaction O
in O
addition O
to O
minor O
but O
atypical O
dysmorphic O
features O
. O
This O
report O
provides O
further O
insight O
into O
the O
pathogenicity O
of O
the O
Xp22.31 O
duplication O
by O
extending O
knowledge O
of O
its O
clinical O
features O
. O
This O
case O
, O
in O
association O
with O
those O
reported O
in O
the O
literature O
, O
indicates O
that O
the O
Xp22.31 O
duplication O
may O
contribute O
to O
cause O
pathological O
phenotypes O
with O
minor O
facial O
dysmorphisms O
, O
microcephaly O
, O
and O
intellectual O
disability O
as O
main O
features O
. O
We O
examined O
the O
potential O
benefits O
of O
neuroimaging O
measurements O
across O
the O
first O
5 O
years O
of O
life O
in O
detecting O
early O
comorbid O
or O
etiological O
signs O
of O
autism O
spectrum O
disorder O
( O
ASD O
) O
. O
In O
particular O
, O
we O
analyzed O
the O
prevalence B-EPI
of O
neuroradiologic O
findings O
in O
routine O
magnetic O
resonance O
imaging O
( O
MRI O
) O
scans O
of O
a O
group O
of O
117 O
ASD O
children O
younger O
than O
5 O
years O
old O
. O
These O
data O
were O
compared O
to O
those O
reported O
in O
typically O
developing O
( O
TD O
) O
children O
. O
MRI O
findings O
in O
children O
with O
ASD O
were O
analyzed O
in O
relation O
to O
their O
cognitive O
level O
, O
severity O
of O
autistic O
symptoms O
, O
and O
the O
presence O
of O
electroencephalogram O
( O
EEG O
) O
abnormalities O
. O
The O
MRI O
was O
rated O
abnormal O
in O
55 O
% O
of O
children O
with O
ASD O
with O
a O
significant O
prevalence B-EPI
in O
the O
high O
- O
functioning O
subgroup O
compared O
to O
TD O
children O
. O
We O
report O
significant O
incidental O
findings O
of O
mega O
cisterna O
magna O
, O
ventricular O
anomalies O
and O
abnormal O
white O
matter O
signal O
intensity O
in O
ASD O
without O
significant O
associations O
between O
these O
MRI O
findings O
and O
EEG O
features O
. O
Based O
on O
these O
results O
we O
discuss O
the O
role O
that O
brain O
MRI O
may O
play O
in O
the O
diagnostic O
procedure O
of O
ASD O
. O
Diabetes O
is O
a O
chronic O
illness O
. O
Hyperglycemia O
is O
the O
characteristic O
of O
this O
disorder O
. O
Diabetes O
is O
a O
global O
crisis O
which O
affects O
the O
economy O
and O
health O
of O
all O
nations O
. O
Over O
the O
last O
decades O
, O
the O
number O
of O
individuals O
living O
with O
diabetes O
has O
significantly O
increased O
worldwide B-LOC
. O
Asia B-LOC
is O
a O
key O
epicenter O
of O
the O
emerging O
diabetes O
epidemic O
, O
with O
China B-LOC
and O
India B-LOC
the O
two O
nations O
having O
the O
highest O
number O
of O
diabetic O
people O
. O
Economic O
development O
, O
modernization O
, O
unhealthy O
diet O
, O
population O
aging O
, O
and O
sedentary O
lifestyles O
are O
the O
major O
factors O
responsible O
for O
the O
increasing O
diabetes O
epidemic O
. O
Diabetes O
is O
associated O
with O
several O
complications O
, O
and O
cardiovascular O
disease O
is O
the O
most O
important O
cause O
of O
morbidity O
and O
mortality O
among O
people O
with O
diabetes O
. O
These O
life O
- O
threatening O
problems O
can O
be O
prevented O
or O
delayed O
by O
proper O
management O
of O
diabetes O
. O
Lifestyle O
modification O
is O
an O
important O
factor O
to O
decrease O
the O
diabetes O
risk O
. O
The O
frequency O
of O
diabetic O
complications O
will O
rise O
if O
there O
is O
a O
lack O
of O
cost O
- O
effective O
and O
sustainable O
interventions O
. O
Hence O
, O
prevention O
of O
diabetes O
and O
its O
complications O
such O
as O
diabetic O
retinopathy O
and O
cardiovascular O
disease O
should O
be O
a O
crucial O
part O
of O
all O
future O
health O
- O
related O
public O
policies O
among O
all O
nations O
. O
This O
review O
summarizes O
current O
epidemiological O
aspects O
of O
diabetes O
in O
the O
world O
along O
with O
its O
complications O
, O
preventive O
measures O
, O
and O
treatment O
. O
Purpose O
of O
review O
The O
goal O
of O
the O
review O
is O
to O
provide O
a O
comprehensive O
overview O
of O
the O
current O
understanding O
of O
the O
mechanisms O
underlying O
variation O
in O
human O
stature O
. O
Recent O
findings O
Human O
height O
is O
an O
anthropometric O
trait O
that O
varies O
considerably O
within O
human O
populations O
as O
well O
as O
across O
the O
globe O
. O
Historically O
, O
much O
research O
focus O
was O
placed O
on O
understanding O
the O
biology O
of O
growth O
plate O
chondrocytes O
and O
how O
modifications O
to O
core O
chondrocyte O
proliferation O
and O
differentiation O
pathways O
potentially O
shaped O
height O
attainment O
in O
normal O
as O
well O
as O
pathological O
contexts O
. O
Recently O
, O
much O
progress O
has O
been O
made O
to O
improve O
our O
understanding O
regarding O
the O
mechanisms O
underlying O
the O
normal O
and O
pathological O
range O
of O
height O
variation O
within O
as O
well O
as O
between O
human O
populations O
, O
and O
today O
, O
it O
is O
understood O
to O
reflect O
complex O
interactions O
among O
a O
myriad O
of O
genetic O
, O
environmental O
, O
and O
evolutionary O
factors O
. O
Indeed O
, O
recent O
improvements O
in O
genetics O
( O
e.g. O
, O
GWAS O
) O
and O
breakthroughs O
in O
functional O
genomics O
( O
e.g. O
, O
whole O
exome O
sequencing O
, O
DNA O
methylation O
analysis O
, O
ATAC O
- O
sequencing O
, O
and O
CRISPR O
) O
have O
shed O
light O
on O
previously O
unknown O
pathways O
/ O
mechanisms O
governing O
pathological O
and O
common O
height O
variation O
. O
Additionally O
, O
the O
use O
of O
an O
evolutionary O
perspective O
has O
also O
revealed O
important O
mechanisms O
that O
have O
shaped O
height O
variation O
across O
the O
planet O
. O
This O
review O
provides O
an O
overview O
of O
the O
current O
knowledge O
of O
the O
biological O
mechanisms O
underlying O
height O
variation O
by O
highlighting O
new O
research O
findings O
on O
skeletal O
growth O
control O
with O
an O
emphasis O
on O
previously O
unknown O
pathways O
/ O
mechanisms O
influencing O
pathological O
and O
common O
height O
variation O
. O
In O
this O
context O
, O
this O
review O
also O
discusses O
how O
evolutionary O
forces O
likely O
shaped O
the O
genomic O
architecture O
of O
height O
across O
the O
globe O
. O
Background O
21 O
- O
Hydroxylase O
deficiency O
( O
21 O
- O
OHD O
) O
caused O
by O
the O
CYP21A2 O
gene O
mutations O
is O
the O
most O
common O
form O
of O
congenital O
adrenal O
hyperplasia O
. O
It O
is O
an O
autosomal O
recessive O
disorder O
that O
results O
in O
defective O
synthesis O
of O
cortisol O
and O
aldosterone O
. O
The O
incidences B-EPI
of O
various O
CYP21A2 O
gene O
mutations O
and O
the O
genotype O
- O
phenotype O
correlations O
vary O
among O
different O
populations O
. O
Materials O
and O
methods O
The O
clinical O
and O
molecular O
data O
of O
22 O
patients O
were O
analyzed O
in O
this O
study O
. O
All O
patients O
were O
recruited O
from O
the O
neonatal O
intensive O
care O
unit O
. O
Locus O
- O
specific O
polymerase O
chain O
reaction O
and O
Sanger O
sequencing O
were O
applied O
to O
identify O
gene O
micro O
- O
conversions O
, O
and O
multiplex O
ligation O
- O
dependent O
probe O
amplification O
was O
used O
to O
detect O
large O
fragment O
deletions O
/ O
conversions O
. O
Then O
, O
the O
genotypes O
were O
categorized O
in O
to O
Null O
, O
A O
, O
B O
, O
C O
, O
and O
D O
groups O
to O
analyze O
the O
relationships O
between O
genotypes O
and O
phenotypes O
. O
Results O
All O
22 O
patients O
were O
classified O
into O
classic O
salt O
wasting O
form O
of O
21 O
- O
OHD O
. O
Molecular O
defects O
were O
detected O
in O
44 O
alleles O
( O
100 O
% O
) O
. O
Micro O
- O
conversion O
mutation O
IVS2 O
- O
13A O
/ O
C O
> O
G O
( O
70.5 O
% O
) O
is O
most O
common O
in O
our O
cohort O
, O
followed O
by O
large O
gene O
deletions O
and O
conversions O
( O
22.7 O
% O
) O
. O
The O
other O
mutations O
present O
were O
p. O
R357 O
W O
( O
4.5 O
% O
) O
and O
E6 O
Cluster O
( O
2.3 O
% O
) O
. O
Genotypes O
of O
22 O
patients O
( O
100 O
% O
) O
were O
consistent O
with O
the O
predictive O
phenotypes O
. O
Conclusion O
In O
this O
study O
, O
we O
identified O
the O
mutation O
spectrum O
of O
CYP21A2 O
gene O
in O
Chinese O
patients O
, O
especially O
the O
younger O
age O
cohort O
in O
pediatrics O
. O
Micro O
- O
conversions O
were O
the O
most O
popular O
mutations O
. O
Moreover O
, O
the O
genotypes O
and O
phenotypes O
were O
well O
correlated O
in O
this O
cohort O
of O
salt O
wasting O
21 O
- O
OHD O
recruited O
from O
neonatal O
intensive O
care O
unit O
. O
Background O
Vitamin O
C O
deficiency O
is O
common O
in O
chronic O
kidney O
disease O
( O
CKD O
) O
due O
to O
losses O
through O
dialysis O
and O
dietary O
intake O
below O
requirement O
. O
We O
investigated O
prevalence B-EPI
of O
vitamin O
C O
deficiency O
and O
impact O
of O
vitamin O
C O
treatment O
in O
deficient O
/ O
insufficient O
patients O
. O
Methods O
A O
prospective O
cohort O
study O
in O
patients O
aged O
1 B-STAT
- I-STAT
18 I-STAT
years O
with O
CKD O
stages O
4 O
and O
5D O
collected O
demographic O
data O
including O
underlying O
disease O
, O
treatment O
, O
and O
anthropometric O
assessment O
. O
Vitamin O
C O
intake O
was O
assessed O
using O
24 O
- O
h O
dietary O
recall O
. O
Hemoglobin O
, O
iron O
status O
, O
serum O
vitamin O
C O
, O
and O
serum O
oxalate O
were O
measured O
at O
baseline O
and O
after O
treatment O
. O
Vitamin O
C O
( O
250 O
mg O
/ O
day O
) O
was O
given O
orally O
for O
3 O
months O
to O
deficient O
/ O
insufficient O
patients O
. O
Results O
Nineteen O
patients O
( O
mean O
age O
12.00 O
± O
4.1 O
years O
) O
showed O
prevalence B-EPI
of O
10.6 O
% O
vitamin O
C O
insufficiency O
and O
78.9 O
% O
deficiency O
. O
There O
were O
no O
associations O
between O
vitamin O
C O
level O
and O
daily O
vitamin O
C O
intake O
( O
p O
= O
0.64 O
) O
or O
nutritional O
status O
( O
p O
= O
0.87 O
) O
. O
Median O
serum O
vitamin O
C O
was O
1.51 O
( O
0.30 O
- O
1.90 O
) O
mg O
/ O
L. O
In O
16 O
patients O
receiving O
treatment O
, O
median O
serum O
vitamin O
C O
increased O
from O
1.30 O
( O
0.23 O
- O
1.78 O
) O
to O
3.22 O
( O
1.77 O
- O
5.96 O
) O
mg O
/ O
L O
( O
p O
= O
0.008 O
) O
without O
increasing O
serum O
oxalate O
( O
79.92 O
( O
56.6 O
- O
106.84 O
) O
vs. O
80.47 O
( O
56.88 O
- O
102.95 O
) O
μmol O
/ O
L O
, O
p O
= O
0.82 O
) O
. O
However O
, O
62.5 O
% O
failed O
to O
achieve O
normal O
vitamin O
C O
levels O
. O
Ordinal O
regression O
analysis O
revealed O
patients O
with O
non O
- O
oligoanuric O
CKD O
were O
less O
likely O
to O
achieve O
normal O
vitamin O
C O
levels O
( O
β O
= O
- O
3.41 O
, O
p O
= O
0.03 O
) O
. O
Conclusion O
We O
describe O
high O
prevalence B-EPI
of O
vitamin O
C O
insufficiency O
/ O
deficiency O
among O
pediatric O
CKD O
patients O
. O
Vitamin O
C O
levels O
could O
not O
be O
solely O
predicted O
by O
nutritional O
status O
or O
daily O
intake O
. O
The O
treatment O
regimen O
raised O
serum O
vitamin O
C O
without O
increasing O
serum O
oxalate O
; O
however O
, O
it O
was O
largely O
insufficient O
to O
normalize O
levels O
, O
particularly O
in O
non O
- O
oligoanuric O
CKD O
. O
Graphical O
abstract O
. O
While O
the O
epidemiology O
of O
Flaviviruses O
has O
been O
extensively O
studied O
in O
most O
of O
the B-LOC
Mediterranean I-LOC
basin I-LOC
, O
little O
is O
known O
about O
the O
current O
situation O
in O
Algeria B-LOC
. O
In O
order O
to O
detect O
the O
circulation O
of O
West B-LOC
Nile I-LOC
( O
WNV O
) O
and O
Usutu O
viruses O
( O
USUV O
) O
in O
Kabylia B-LOC
, O
165 O
sera O
were O
collected O
from O
two O
wild O
birds O
species O
, O
namely O
the O
long O
distance O
migrant O
Turdus O
philomelos O
( O
song O
thrush O
) O
( O
n O
= O
92 O
) O
and O
the O
resident O
Passer O
domesticus O
( O
house O
sparrow O
) O
( O
n O
= O
73 O
) O
. O
A O
total O
of O
154 O
sera O
were O
first O
analyzed O
by O
commercial O
competition O
ELISA O
. O
WNV O
and O
USUV O
micro O
- O
neutralization O
tests O
were O
performed O
on O
all O
c O
- O
ELISA O
positive O
sera O
and O
all O
samples O
with O
poor O
volume O
. O
Overall O
, O
7.8 O
% O
( O
CI95 O
% O
: O
3.5 O
- O
11.9 O
) O
were O
positive O
by O
c O
- O
ELISA O
. O
Positive O
results O
were O
detected O
in O
12.5 O
% O
( O
CI95 O
% O
: O
5.6 O
- O
19.4 O
) O
of O
song O
thrushes O
and O
1.5 O
% O
( O
CI95 O
% O
: O
0.0 O
- O
4.5 O
) O
for O
sparrow O
. O
Micro O
- O
neutralization O
tests O
revealed O
an O
overall O
seroprevalence O
of O
6.7 O
% O
for O
WNV O
( O
CI95 O
% O
: O
2.9 O
- O
10.3 O
) O
, O
Neutralizing O
antibodies O
were O
found O
in O
8.7 O
% O
( O
CI95 O
% O
: O
3.0 O
- O
14.4 O
) O
for O
song O
thrushes O
and O
in O
4.1 O
% O
( O
CI95 O
% O
: O
0.0 O
- O
8.7 O
) O
of O
sparrows O
. O
The O
current O
study O
demonstrates O
significant O
seroprevalence O
of O
WNV O
antibodies O
in O
wild O
birds O
in O
Algeria B-LOC
. O
The O
prevalence B-EPI
of O
congenital O
hydrocephalus O
has O
been O
estimated O
at O
1.1 B-STAT
per I-STAT
1000 I-STAT
infants I-STAT
when O
including O
cases O
diagnosed O
before O
1 O
year O
of O
age O
after O
exclusion O
of O
neural O
tube O
defects O
. O
Classification O
criteria O
are O
based O
either O
on O
CSF O
dynamics O
, O
pathophysiological O
mechanisms O
or O
associated O
lesions O
. O
Whereas O
inherited O
syndromic O
hydrocephalus O
has O
been O
associated O
with O
more O
than O
100 O
disease O
- O
causing O
genes O
, O
only O
four O
genes O
are O
currently O
known O
to O
be O
linked O
to O
congenital O
hydrocephalus O
either O
isolated O
or O
as O
a O
major O
clinical O
feature O
: O
L1CAM O
, O
AP1S2 O
, O
MPDZ O
and O
CCDC88C. O
In O
the O
past O
10 O
years O
, O
pathogenic O
variants O
in O
CCDC88C O
have O
been O
documented O
but O
the O
neuropathology O
remains O
virtually O
unknown O
. O
We O
report O
the O
neuropathology O
of O
two O
foetuses O
from O
one O
family O
harbouring O
two O
novel O
compound O
heterozygous O
pathogenic O
variants O
in O
the O
CCDC88C O
gene O
: O
a O
maternally O
inherited O
indel O
in O
exon O
22 O
, O
c.3807_3809delinsACCT;p.(Gly1270Profs*53 O
) O
and O
a O
paternally O
inherited O
deletion O
of O
exon O
23 O
, O
c.3967-?_c.4112-?;p.(Leu1323Argfs*10 O
) O
. O
Medical O
termination O
of O
pregnancy O
was O
performed O
at O
18 O
and O
23 O
weeks O
of O
gestation O
for O
severe O
bilateral O
ventriculomegaly O
. O
In O
both O
fetuses O
, O
brain O
lesions O
consisted O
of O
multifocal O
atresia O
- O
forking O
along O
the O
aqueduct O
of O
Sylvius O
and O
the O
central O
canal O
of O
the O
medulla O
, O
periventricular O
neuronal O
heterotopias O
and O
choroid O
plexus O
hydrops O
. O
The O
second O
fetus O
also O
presented O
lumbar O
myelomeningocele O
, O
left O
diaphragmatic O
hernia O
and O
bilateral O
renal O
agenesis O
. O
CCDC88C O
encodes O
the O
protein O
DAPLE O
which O
contributes O
to O
ependymal O
cell O
planar O
polarity O
by O
inhibiting O
the O
non O
- O
canonical O
Wnt O
signaling O
pathway O
and O
interacts O
with O
MPDZ O
and O
PARD3 O
. O
Interestingly O
, O
heterozygous O
variants O
in O
PARD3 O
result O
in O
neural O
tube O
defects O
by O
defective O
tight O
junction O
formation O
and O
polarization O
process O
of O
the O
neuroepithelium O
. O
Besides O
, O
during O
organ O
formation O
Wnt O
signalling O
is O
a O
prerequisite O
for O
planar O
cell O
polarity O
pathway O
activation O
, O
and O
mutations O
in O
planar O
cell O
polarity O
genes O
lead O
to O
heart O
, O
lung O
and O
kidney O
malformations O
. O
Hence O
, O
candidate O
variants O
in O
CCDC88C O
should O
be O
carefully O
considered O
whether O
brain O
lesions O
are O
isolated O
or O
associated O
with O
malformations O
suspected O
to O
result O
from O
disorders O
of O
planar O
cell O
polarity O
. O
Background O
Vitamin O
D O
deficiency O
is O
highly O
prevalent B-EPI
in O
children O
with O
intestinal O
failure O
( O
IF O
) O
who O
receive O
parenteral O
nutrition O
( O
PN O
) O
, O
but O
data O
on O
vitamin O
D O
status O
after O
achieving O
enteral O
autonomy O
( O
EA O
) O
are O
limited O
. O
We O
aimed O
to O
evaluate O
the O
prevalence B-EPI
of O
vitamin O
D O
deficiency O
in O
this O
population O
while O
exploring O
clinical O
variables O
that O
may O
be O
associated O
with O
its O
development O
. O
Methods O
A O
retrospective O
review O
was O
performed O
on O
29 O
children O
with O
IF O
who O
had O
achieved O
EA O
. O
Deficiency O
was O
defined O
as O
a O
mean O
serum O
25 O
- O
hydroxyvitamin O
D O
< O
30 O
ng O
/ O
ml O
. O
Data O
results O
Sixty B-STAT
- O
six O
percent O
of O
children O
had O
at O
least O
one O
deficient O
level O
during O
the O
study O
period O
, O
with O
38 O
% O
being O
deficient O
based O
on O
the O
mean O
vitamin O
D O
levels O
. O
Eighty B-STAT
- O
four O
percent O
had O
radiologic O
evidence O
of O
osteopenia O
. O
Compared O
with O
the O
sufficient O
group O
( O
n=18 O
) O
, O
the O
deficient O
group O
( O
n=11 O
) O
received O
higher O
daily O
mean O
vitamin O
D O
doses O
( O
2246 O
vs O
920 O
IU O
; O
P=.02 O
) O
, O
had O
shorter O
remnant O
small O
- O
bowel O
length O
( O
53.8 O
vs O
82.1 O
cm O
; O
P=.03 O
) O
, O
and O
were O
PN O
dependent O
for O
a O
longer O
duration O
( O
1.3 O
vs O
0.58 O
years O
; O
P=.01 O
) O
. O
Univariate O
analyses O
revealed O
longer O
remnant O
gut O
length O
( O
odds O
ratio O
[ O
OR O
] O
= O
1.03 O
; O
P=.04 O
) O
and O
shorter O
duration O
of O
PN O
( O
OR O
= O
0.26 O
; O
P=.04 O
) O
to O
be O
significantly O
associated O
with O
sufficient O
vitamin O
D O
status O
. O
Conclusion O
Vitamin O
D O
deficiency O
and O
osteopenia O
are O
highly O
prevalent B-EPI
in O
pediatric O
patients O
with O
a O
history O
of O
IF O
who O
have O
achieved O
EA O
, O
despite O
enteral O
supplementation O
with O
higher O
than O
standard O
doses O
. O
Shorter O
remnant O
small O
- O
bowel O
length O
and O
longer O
duration O
of O
PN O
were O
associated O
with O
vitamin O
D O
deficiency O
. O
These O
findings O
emphasize O
the O
importance O
of O
prolonged O
surveillance O
and O
highlight O
the O
need O
for O
alternate O
dosing O
regimens O
. O
Enshi O
prefecture O
of O
Hubei B-LOC
Province I-LOC
is O
well O
known O
for O
human O
selenium O
( O
Se O
) O
poisoning O
in O
the O
early O
1960s O
in O
China B-LOC
. O
Sporadic O
cases O
of O
Se O
poisoning O
in O
livestocks O
are O
still O
being O
found O
. O
In O
this O
study O
, O
Se O
levels O
in O
water O
, O
cropland O
soils O
and O
various O
crops O
from O
high O
- O
Se O
areas O
of O
Enshi O
were O
measured O
to O
investigate O
the O
distribution O
and O
bioavailability O
of O
Se O
in O
the O
environments O
, O
as O
well O
as O
probable O
daily O
intake O
( O
PDI O
) O
of O
Se O
for O
local O
residents O
. O
The O
total O
Se O
in O
surface O
water O
ranged O
from O
2.0 O
to O
519.3μg O
/ O
L O
with O
a O
geometric O
mean O
of O
46.0±127.8 O
μg O
/ O
L O
( O
n=48 O
) O
, O
70.5 O
- O
99.5 O
% O
of O
which O
was O
present O
in O
the O
form O
of O
Se(VI O
) O
. O
The O
soil O
Se O
concentration O
varied O
from O
2.89 O
to O
87.3 O
μg O
/ O
g O
with O
a O
geometric O
mean O
of O
9.36±18.6 O
μg O
/ O
g O
( O
n=45 O
) O
, O
and O
most O
of O
Se O
was O
associated O
with O
organic O
matter O
( O
OM O
- O
Se O
) O
. O
The O
total O
Se O
in O
rice O
, O
corn O
, O
and O
vegetable O
samples O
were O
2.11±2.87 O
μg O
/ O
g O
( O
n=21 O
) O
, O
3.76±11.6 O
μg O
/ O
g O
( O
n=16 O
) O
, O
and O
2.09±3.38 O
μg O
/ O
g O
( O
n=25 O
) O
, O
respectively O
. O
Stream O
water O
Se O
is O
likely O
leached O
from O
carbonaceous O
shale O
and O
mine O
wastes O
, O
leading O
to O
Se O
accumulation O
in O
paddy O
soils O
. O
OM O
- O
Se O
may O
play O
an O
important O
role O
in O
Se O
uptake O
by O
rice O
plant O
in O
high O
- O
Se O
area O
of O
Enshi O
. O
The O
PDI O
of O
Se O
is O
approximately O
2144 O
μg O
/ O
day O
, O
and O
Se O
concentration O
in O
blood O
is O
estimated O
at O
about O
3248 O
μg O
/ O
L O
, O
posing O
a O
potential O
chronic O
Se O
poisoning O
risk O
to O
local O
residents O
. O
Cereal O
consumption O
( O
48.5 O
% O
) O
makes O
a O
great O
contribution O
to O
human O
daily O
Se O
intake O
, O
followed O
by O
vegetables O
( O
36.6 O
% O
) O
, O
meats O
( O
8.5 O
% O
) O
, O
and O
drinking O
water O
( O
6.4 O
% O
) O
. O
However O
, O
when O
assessing O
health O
risk O
on O
human O
in O
high O
- O
Se O
areas O
, O
the O
contribution O
of O
drinking O
water O
to O
daily O
Se O
intake O
can O
not O
be O
ignored O
due O
to O
high O
Se O
content O
and O
dominant O
Se(VI O
) O
species O
. O
Local O
inhabitants O
should O
be O
advised O
not O
to O
grow O
crops O
in O
high O
- O
Se O
lands O
or O
irrigate O
using O
high O
- O
Se O
water O
. O
If O
possible O
, O
they O
should O
drink O
pipe O
water O
and O
consume O
foods O
mixed O
with O
those O
from O
outside O
the O
high O
- O
Se O
areas O
. O
Hearing O
loss O
( O
HL O
) O
is O
an O
extra O
- O
skeletal O
manifestation O
of O
the O
connective O
tissue O
disorder O
osteogenesis O
imperfecta O
( O
OI O
) O
. O
Systematic O
evaluation O
of O
the O
prevalence B-EPI
and O
characteristics O
of O
HL O
in O
COL1A1 O
/ O
COL1A2 O
- O
related O
OI O
will O
contribute O
to O
a O
better O
clinical O
management O
of O
individuals O
with O
OI O
. O
We O
collected O
and O
analyzed O
pure O
- O
tone O
audiometry O
data O
from O
312 O
individuals O
with O
OI O
who O
were O
enrolled O
in O
the O
Linked O
Clinical O
Research O
Centers O
and O
the O
Brittle O
Bone O
Disorders O
Consortium O
. O
The O
prevalence B-EPI
, O
type O
, O
and O
severity O
of O
HL O
in O
COL1A1 O
/ O
COL1A2 O
- O
related O
OI O
are O
reported O
. O
We O
show O
that O
the O
prevalence B-EPI
of O
HL O
in O
OI O
is O
28 O
% O
and O
increased O
with O
age O
in O
Type O
I O
OI O
but O
not O
in O
Types O
III O
and O
IV O
. O
Individuals O
with O
OI O
Types O
III O
and O
IV O
are O
at O
a O
higher O
risk O
to O
develop O
HL O
in O
the O
first O
decade O
of O
life O
when O
compared O
to O
OI O
Type O
I. O
We O
also O
show O
that O
the O
prevalence B-EPI
of O
SNHL O
is O
higher O
in O
females O
with O
OI O
compared O
to O
males O
. O
This O
study O
reveals O
new O
insights O
regarding O
prevalence B-EPI
of O
HL O
in O
OI O
including O
a O
lower O
general O
prevalence B-EPI
of O
HL O
in O
COL1A1 O
/ O
COL1A2 O
- O
related O
OI O
than O
previously O
reported O
( O
28.3 O
vs. O
65 O
% O
) O
and O
high O
prevalence B-EPI
of O
SNHL O
in O
females O
. O
Our O
data O
support O
the O
need O
in O
early O
routine O
hearing O
evaluation O
in O
all O
types O
of O
OI O
that O
can O
be O
adjusted O
to O
the O
severity O
of O
the O
skeletal O
disease O
. O
Introduction O
: O
' O
Chronic O
inflammatory O
immune O
- O
related O
skin O
disease O
' O
( O
ISDs O
) O
is O
an O
umbrella O
term O
grouping O
together O
heterogeneous O
entities O
characterized O
by O
chronic O
inflammation O
potentially O
involving O
the O
whole O
skin O
. O
We O
are O
not O
covering O
all O
ISDs O
in O
this O
review O
, O
but O
take O
a O
few O
as O
the O
most O
representative O
, O
including O
nonbullous O
and O
bullous O
diseases O
. O
The O
question O
we O
are O
aiming O
to O
address O
can O
be O
summarized O
as O
follows O
: O
' O
despite O
the O
differences O
, O
is O
it O
possible O
to O
define O
some O
unifying O
epidemiologic O
characteristics O
and O
shared O
progression O
pathways O
which O
can O
guide O
the O
organization O
of O
healthcare O
? O
' O
Areas O
covered O
: O
This O
review O
covers O
incidence B-EPI
, O
prevalence B-EPI
, O
risk O
factors O
and O
prognosis O
of O
psoriasis O
, O
atopic O
dermatitis O
( O
AD O
) O
, O
pemphigus O
and O
pemphigoid O
. O
Medline O
, O
Embase O
and O
the O
Cochrane O
Library O
were O
searched O
for O
papers O
published O
between O
January O
2005 O
and O
December O
2019 O
. O
Expert O
opinion O
: O
ISDs O
epidemiology O
varies O
according O
to O
the O
ISD O
type O
, O
age O
, O
sex O
, O
climate O
, O
and O
sociodemographic O
variables O
. O
AD O
and O
psoriasis O
pose O
a O
considerable O
public O
health O
burden O
owing O
to O
their O
high O
prevalence B-EPI
worldwide B-LOC
and O
morbidity O
. O
Their O
secular O
trend O
of O
increasing O
incidence B-EPI
points O
to O
a O
role O
for O
environmental O
factors O
and O
gene O
- O
environment O
interactions O
. O
Bullous O
diseases O
are O
much O
rarer O
, O
with O
limited O
data O
available O
. O
Worldwide O
, O
the O
leading O
cause O
of O
skin O
disease O
disability O
- O
adjusted O
life O
- O
years O
( O
DALYs O
) O
is O
attributable O
to O
AD O
. O
Future O
research O
should O
focus O
on O
risk O
factors O
and O
prevention O
at O
the O
global O
level O
. O
Background O
Neurological O
involvement O
due O
to O
intraspinal O
extension O
in O
sacrococcygeal O
malignant O
germ O
cell O
tumors O
( O
SC O
- O
MGCTs O
) O
has O
rarely O
been O
reported O
. O
Aim O
To O
evaluate O
the O
incidence B-EPI
, O
presentation O
, O
management O
and O
the O
outcome O
of O
patients O
of O
SC O
- O
MGCT O
with O
intraspinal O
extension O
. O
Materials O
and O
methods O
Case O
records O
of O
all O
cases O
of O
SC O
- O
MGCT O
from O
2001 O
to O
2008 O
, O
were O
reviewed O
to O
identify O
cases O
with O
vertebral O
involvement O
and O
intraspinal O
extension O
. O
They O
were O
evaluated O
in O
terms O
of O
their O
presentation O
, O
response O
to O
therapy O
, O
extent O
of O
surgical O
resection O
, O
recovery O
of O
neurological O
symptoms O
and O
outcome O
. O
Results O
Of O
the O
31 O
cases O
of O
SC O
- O
MGCT O
, O
5 B-STAT
( O
16 O
% O
) O
had O
intraspinal O
extension O
. O
Age O
ranged O
from O
12 O
to O
84 O
months O
( O
median O
24 O
months O
) O
. O
Four O
patients O
had O
Altman O
type O
4 O
disease O
( O
stage O
4 O
) O
and O
1 O
had O
Altman O
type O
3 O
( O
stage O
3 O
) O
disease O
. O
The O
intraspinal O
extension O
in O
all O
patients O
was O
detected O
on O
contrast O
CT O
scan O
. O
Patients O
presented O
with O
neurological O
symptoms O
in O
the O
form O
of O
lower O
limb O
paresis O
( O
80 O
% O
) O
, O
bowel O
and O
bladder O
( O
20 O
% O
) O
incontinence O
. O
All O
the O
tumors O
responded O
to O
pre O
- O
operative O
chemotherapy O
. O
Gross O
complete O
local O
resection O
could O
be O
achieved O
in O
4(80 O
% O
) O
. O
Neurological O
recovery O
was O
complete O
in O
all O
except O
for O
persisting O
neurogenic O
bladder O
in O
one O
. O
During O
follow O
up O
of O
3 O
- O
32 O
months O
, O
all O
were O
alive O
with O
no O
recurrence O
. O
Conclusions O
SC O
- O
MGCT O
presenting O
with O
neurological O
deficits O
due O
to O
intraspinal O
extension O
is O
usually O
advanced O
disease O
. O
These O
patients O
respond O
to O
chemotherapy O
and O
surgical O
resection O
and O
most O
have O
complete O
neurological O
improvement O
. O
Middle O
ear O
barotrauma O
( O
MEB O
) O
is O
a O
common O
complication O
of O
hyperbaric O
oxygen O
( O
HBO2 O
) O
therapy O
. O
It O
has O
been O
reported O
in O
more O
than O
40 B-STAT
% O
of O
HBO2 O
treatments O
and O
can O
interrupt O
the O
sequence O
of O
HBO2 O
. O
MEB O
may O
lead O
to O
pain O
, O
tympanic O
membrane O
rupture O
, O
and O
even O
hearing O
loss O
. O
The O
aim O
of O
this O
study O
was O
to O
determine O
if O
pretreatment O
with O
intranasal O
fluticasone O
and O
oxymetazoline O
affected O
the O
incidence B-EPI
of O
MEB O
. O
We O
conducted O
a O
retrospective O
chart O
review O
of O
subjects O
undergoing O
HBO2 O
at O
our O
institution O
between O
February O
1 O
, O
2014 O
, O
and O
May O
31 O
, O
2019 O
. O
Subjects O
in O
the O
fluticasone O
/ O
oxymetazoline O
( O
FOT O
) O
treatment O
group O
used O
intranasal O
fluticasone O
50 B-STAT
mcg I-STAT
two I-STAT
times I-STAT
per I-STAT
day I-STAT
and I-STAT
oxymetazoline O
0.05 B-STAT
% I-STAT
one O
spray O
two B-STAT
times I-STAT
per I-STAT
day I-STAT
beginning I-STAT
48 I-STAT
hours O
prior O
to O
initial O
HBO2 O
. O
Oxymetazoline O
was O
discontinued O
after O
four O
days O
. O
Fluticasone O
was O
continued O
for O
the O
duration O
of O
HBO2 O
therapy O
. O
A O
total O
of O
154 O
unique O
subjects O
underwent O
5,683 O
HBO2 O
treatments O
: O
39 O
unique O
subjects O
in O
the O
FOT O
group O
underwent O
1,501 O
HBO2 O
; O
115 O
unique O
subjects O
in O
the O
nFOT O
( O
no O
oxymetazoline O
or O
fluticasone O
treatment O
) O
group O
underwent O
4,182 O
HBO2 O
treatments O
. O
The O
incidence B-EPI
of O
MEB O
was O
15.4 O
% O
in O
the O
FOT O
group O
and O
16.2 O
% O
in O
the O
nFOT O
group O
. O
This O
was O
not O
a O
statistically O
significant O
difference O
( O
OR O
= O
0.77 O
; O
p O
= O
0.636 O
) O
. O
Treatment O
pressure O
, O
age O
over O
65 O
years O
, O
male O
sex O
, O
and O
BMI O
were O
not O
associated O
with O
a O
difference O
in O
MEB O
incidence B-EPI
. O
In O
summary O
, O
pretreatment O
with O
intranasal O
oxymetazoline O
and O
fluticasone O
in O
patients O
undergoing O
HBO2 O
did O
not O
significantly O
reduce O
MEB O
. O
More O
investigation O
with O
larger O
numbers O
of O
participants O
and O
prospective O
studies O
could O
further O
clarify O
this O
issue O
. O
BACKGROUND O
: O
The O
incidence B-EPI
of O
Taralomyces O
marneffei O
infection O
in O
HIV O
- O
infected O
individuals O
has O
been O
decreasing O
, O
whereas O
its O
rate O
is O
rising O
among O
non O
- O
HIV O
immunodeficient O
persons O
, O
particularly O
patients O
with O
anti O
- O
interferon O
- O
gamma O
autoantibodies O
. O
T. O
marneffei O
usually O
causes O
invasive O
and O
disseminated O
infections O
, O
including O
fungemia O
. O
T. O
marneffei O
oro O
- O
pharyngo O
- O
laryngitis O
is O
an O
unusual O
manifestation O
of O
talaromycosis O
. O
CASE O
PRESENTATION O
: O
A O
52 O
- O
year O
- O
old O
Thai O
woman O
had O
been O
diagnosed O
anti O
- O
IFNɣ O
autoantibodies O
for O
4 O
years O
. O
She O
had O
a O
sore O
throat O
, O
odynophagia O
, O
and O
hoarseness O
for O
3 O
weeks O
. O
She O
also O
had O
febrile O
symptoms O
and O
lost O
5 O
kg O
in O
weight O
. O
Physical O
examination O
revealed O
marked O
swelling O
and O
hyperemia O
of O
both O
sides O
of O
the O
tonsils O
, O
the O
uvula O
and O
palatal O
arches O
including O
a O
swelling O
of O
the O
epiglottis O
, O
and O
arytenoid O
. O
The O
right O
tonsillar O
biopsy O
exhibited O
a O
few O
intracellular O
oval O
and O
elongated O
yeast O
- O
like O
organisms O
with O
some O
central O
transverse O
septum O
seen O
, O
which O
subsequently O
grew O
a O
few O
colonies O
of O
T. O
marneffei O
on O
fungal O
cultures O
. O
The O
patient O
received O
amphotericin O
B O
deoxycholate O
45 O
mg O
/ O
dayfor O
1 B-STAT
weeks O
, O
followed O
by O
oral O
itraconazole O
400 O
mg O
/ O
day O
for O
several O
months O
. O
Her O
symptoms O
completely O
resolved O
without O
complication O
. O
CONCLUSION O
: O
In O
patients O
with O
anti O
- O
IFN O
- O
ɣ O
autoantibodies O
, O
T. O
marneffei O
can O
rarely O
cause O
a O
local O
infection O
involving O
oropharynx O
and O
larynx O
. O
Fungal O
culture O
and O
pathological O
examination O
are O
warranted O
for O
diagnosis O
T. O
marneffei O
oro O
- O
pharyngo O
- O
laryngitis O
. O
This O
condition O
requires O
a O
long O
term O
antifungal O
therapy O
. O
Background O
and O
objective O
To O
understand O
the O
microvascular O
abnormalities O
in O
cystoid O
macular O
edema O
( O
CME O
) O
in O
gyrate O
atrophy O
. O
Patients O
and O
methods O
Spectral O
- O
domain O
optical O
coherence O
tomography O
( O
SD O
- O
OCT O
) O
and O
OCT O
angiography O
( O
OCTA O
) O
were O
used O
in O
four O
consecutive O
female O
patients O
( O
eight O
eyes O
) O
with O
clinically O
and O
biochemistry O
- O
confirmed O
cases O
of O
gyrate O
atrophy O
and O
associated O
CME O
. O
Foveal O
avascular O
zone O
( O
FAZ O
) O
area O
and O
macular O
vessel O
density O
percentage O
were O
calculated O
and O
compared O
with O
normal O
subjects O
. O
Results O
The O
average O
age O
was O
20 O
years O
( O
range O
: O
13 O
years O
to O
32 O
years O
) O
. O
The O
mean O
refractive O
error O
was O
-6.5 O
diopters O
( O
D O
) O
( O
range O
: O
-1.0 O
D O
to O
-11.0 O
D O
) O
. O
The O
average O
central O
macular O
thickness O
was O
509 O
μm O
( O
range O
: O
291 O
μm O
to O
750 O
μm O
) O
. O
OCTA O
showed O
an O
enlarged O
FAZ O
in O
the O
deep O
capillary O
plexus O
( O
DCP O
) O
with O
presence O
of O
hyporeflective O
cysts O
in O
both O
the O
superficial O
and O
deep O
capillary O
layers O
corresponding O
to O
CME O
. O
Compared O
to O
the O
normal O
subjects O
, O
the O
mean O
FAZ O
area O
was O
enlarged O
and O
macular O
vessel O
density O
was O
reduced O
in O
both O
the O
superficial O
capillary O
plexus O
and O
DCP O
; O
this O
was O
statistically O
significant O
( O
P O
< O
.05 O
) O
. O
En O
face O
OCT O
of O
the O
DCPs O
showed O
classical O
hyporeflective O
honeycomb O
pattern O
delineating O
the O
structural O
pattern O
of O
CME O
in O
the O
inner O
plexiform O
and O
outer O
plexiform O
layer O
. O
Conclusion O
OCTA O
helps O
understand O
the O
basic O
pathophysiologic O
mechanisms O
in O
gyrate O
atrophy O
of O
choroid O
as O
well O
as O
etiology O
for O
CME O
and O
macular O
schisis O
. O
[ O
Ophthalmic O
Surg O
Lasers O
Imaging O
Retina O
. O
2019;50:423 O
- O
427 O
. O
] O
. O
Larsen O
syndrome O
( O
OMIM O
150250 O
) O
was O
first O
described O
in O
1950 O
as O
an O
entity O
characterized O
by O
distinct O
facial O
features O
and O
dislocations O
of O
the O
multiple O
large O
joint O
, O
and O
cleft O
palate O
, O
hearing O
loss O
, O
and O
spinal O
abnormalities O
were O
occasionally O
observed O
. O
The O
prevalence B-EPI
of O
Larsen O
syndrome O
is O
estimated O
to O
be O
one O
in O
100,000 O
live O
births O
. O
Management O
of O
multiple O
large O
- O
joint O
dislocations O
often O
proves O
difficult O
with O
a O
tendency O
toward O
recurrence O
, O
particularly O
if O
a O
patient O
has O
complete O
dislocation O
of O
the O
knee O
.We O
treated O
a O
boy O
with O
the O
clinical O
phenotype O
of O
Larsen O
syndrome O
using O
10 O
orthopedic O
procedures O
, O
but O
failed O
to O
achieve O
a O
satisfactory O
outcome O
. O
The O
aim O
of O
this O
report O
is O
to O
review O
the O
surgical O
course O
and O
report O
results O
of O
surgical O
treatments O
for O
this O
patient O
with O
12 O
years O
of O
follow O
- O
up O
. O
Objective O
Dominant O
optic O
atrophy O
( O
DOA O
) O
is O
the O
most O
common O
inherited O
optic O
neuropathy O
, O
with O
a O
prevalence B-EPI
of O
1:12,000 B-STAT
to O
1:25,000 O
. O
OPA1 O
mutations O
are O
found O
in O
70 O
% O
of O
DOA O
patients O
, O
with O
a O
significant O
number O
remaining O
undiagnosed O
. O
Methods O
We O
screened O
286 O
index O
cases O
presenting O
optic O
atrophy O
, O
negative O
for O
OPA1 O
mutations O
, O
by O
targeted O
next O
generation O
sequencing O
or O
whole O
exome O
sequencing O
. O
Pathogenicity O
and O
molecular O
mechanisms O
of O
the O
identified O
variants O
were O
studied O
in O
yeast O
and O
patient O
- O
derived O
fibroblasts O
. O
Results O
Twelve O
cases O
( O
4 O
% O
) O
were O
found O
to O
carry O
novel O
variants O
in O
AFG3L2 O
, O
a O
gene O
that O
has O
been O
associated O
with O
autosomal O
dominant O
spinocerebellar O
ataxia O
28 O
( O
SCA28 O
) O
. O
Half O
of O
cases O
were O
familial O
with O
a O
dominant O
inheritance O
, O
whereas O
the O
others O
were O
sporadic O
, O
including O
de O
novo O
mutations O
. O
Biallelic O
mutations O
were O
found O
in O
3 O
probands O
with O
severe O
syndromic O
optic O
neuropathy O
, O
acting O
as O
recessive O
or O
phenotype O
- O
modifier O
variants O
. O
All O
the O
DOA O
- O
associated O
AFG3L2 O
mutations O
were O
clustered O
in O
the O
ATPase O
domain O
, O
whereas O
SCA28 O
- O
associated O
mutations O
mostly O
affect O
the O
proteolytic O
domain O
. O
The O
pathogenic O
role O
of O
DOA O
- O
associated O
AFG3L2 O
mutations O
was O
confirmed O
in O
yeast O
, O
unraveling O
a O
mechanism O
distinct O
from O
that O
of O
SCA28 O
- O
associated O
AFG3L2 O
mutations O
. O
Patients O
' O
fibroblasts O
showed O
abnormal O
OPA1 O
processing O
, O
with O
accumulation O
of O
the O
fission O
- O
inducing O
short O
forms O
leading O
to O
mitochondrial O
network O
fragmentation O
, O
not O
observed O
in O
SCA28 O
patients O
' O
cells O
. O
Interpretation O
This O
study O
demonstrates O
that O
mutations O
in O
AFG3L2 O
are O
a O
relevant O
cause O
of O
optic O
neuropathy O
, O
broadening O
the O
spectrum O
of O
clinical O
manifestations O
and O
genetic O
mechanisms O
associated O
with O
AFG3L2 O
mutations O
, O
and O
underscores O
the O
pivotal O
role O
of O
OPA1 O
and O
its O
processing O
in O
the O
pathogenesis O
of O
DOA O
. O
ANN O
NEUROL O
2020 O
ANN O
NEUROL O
2020;88:18 O
- O
32 O
. O
Objective O
To O
analyze O
the O
results O
and O
follow O
up O
data O
of O
screening O
for O
newborn O
organic O
aciduria O
in O
Zhejiang B-LOC
province I-LOC
. O
Methods O
The O
results O
and O
follow O
- O
up O
data O
of O
1 B-STAT
861 I-STAT
262 I-STAT
newborns O
from O
Zhejiang B-LOC
province O
undergoing O
screening O
for O
organic O
aciduria O
during O
January O
2009 O
and O
December O
2016 O
were O
retrospectively O
analyzed O
. O
The O
acylcarnitine O
spectrum O
in O
urine O
samples O
was O
detected O
by O
tandem O
mass O
spectrum O
( O
MS O
/ O
MS O
) O
and O
the O
positive O
patients O
were O
confirmed O
by O
urine O
gas O
chromatography O
mass O
spectrometry O
and/or O
gene O
analysis O
. O
Results O
Ninety O
two O
cases O
of O
organic O
aciduria O
were O
confirmed O
with O
a O
prevalence B-EPI
of O
1:20 B-STAT
200 I-STAT
. I-STAT
Among O
40 O
cases O
of O
methylmalonic O
academia O
( O
MMA O
) O
, O
13 B-STAT
( O
32.5 O
% O
) O
were O
of O
MMA O
simple O
type O
and O
27 B-STAT
( O
67.5 O
% O
) O
were O
combined O
type O
. O
Genetic O
analysis O
showed O
6 O
cases O
of O
MUT O
type O
and O
1 O
case O
of O
CblB O
type O
out O
of O
7 O
patients O
with O
MMA O
simple O
type O
, O
10 O
cases O
of O
CblC O
and O
1 O
case O
of O
CblF O
out O
of O
11 O
patients O
with O
combined O
type O
, O
respectively O
. O
Six O
patients O
had O
propionic O
academia O
with O
a O
prevalence B-EPI
of O
1:310 B-STAT
200 I-STAT
, I-STAT
7 I-STAT
had O
isovaleric O
academia O
( O
1:265 B-STAT
900 I-STAT
) I-STAT
, O
6 O
had O
glutaric O
academia O
type O
1 B-STAT
( I-STAT
1:310 B-STAT
200 I-STAT
) I-STAT
, O
27 O
had O
3 O
- O
methylcrotonyl O
- O
CoA O
carboxylase O
deficiency O
( O
MCC O
, O
1:68 B-STAT
900 I-STAT
) I-STAT
, O
1 B-STAT
had I-STAT
3 I-STAT
- O
hydroxy-3 O
- O
methylglutaric O
aciduria O
( O
1:1 B-STAT
861 I-STAT
300 I-STAT
) I-STAT
, O
2 O
had O
β O
- O
ketothiolase O
deficiency O
( O
1:960 B-STAT
600 I-STAT
) I-STAT
, O
and O
3 O
had O
biotinidase O
deficiency O
/ O
holocarboxylase O
synthetase O
deficiency O
( O
1:620 B-STAT
400 I-STAT
) I-STAT
. O
Thirty O
- O
one O
patients O
had O
a O
disease O
onset O
at O
neonatal O
period O
, O
and O
15 O
at O
post O
- O
neonatal O
period O
. O
Thirty O
- O
three O
patients O
had O
brain O
involvements O
or O
cranial O
imaging O
disorders O
. O
Three O
patients O
with O
MMA O
had O
kidney O
diseases O
or O
heomlytic O
uremic O
syndrome O
, O
and O
3 O
had O
myocardial O
impairments O
. O
Twenty O
patients O
died O
during O
the O
follow O
- O
up O
. O
Conclusions O
MMA O
is O
the O
most O
common O
newborn O
organic O
aciduria O
in O
Zhejiang B-LOC
province I-LOC
. O
Except O
MCC O
, O
most O
organic O
aciduria O
may O
lead O
to O
metabolism O
decompensation O
, O
complications O
or O
even O
death O
. O
Oral O
dexamethasone O
mini O
pulse O
( O
OMP O
) O
is O
an O
established O
treatment O
modality O
for O
active O
vitiligo O
. O
Cyclosporine O
may O
have O
therapeutic O
role O
in O
active O
vitiligo O
but O
current O
evidence O
supporting O
its O
role O
is O
scarce O
. O
The O
objective O
of O
study O
was O
to O
compare O
the O
efficacy O
and O
safety O
of O
oral O
cyclosporine O
with O
OMP O
in O
patients O
of O
active O
vitiligo O
. O
Fifty O
patients O
with O
active O
vitiligo O
were O
randomized O
into O
two O
groups O
of O
25 O
patients O
. O
Group O
1 O
was O
treated O
with O
OMP O
( O
2.5 O
mg O
dexamethasone O
) O
on O
two O
consecutive O
days O
/ O
week O
for O
4 O
months O
while O
group O
2 O
was O
treated O
with O
cyclosporine O
( O
3 O
mg O
/ O
kg O
/ O
day O
) O
for O
4 O
months O
. O
Laboratory O
monitoring O
was O
performed O
as O
per O
the O
prevalent B-EPI
protocol O
. O
The O
patients O
were O
followed O
up O
for O
another O
2 O
months O
after O
stopping O
treatment O
. O
Arrest O
of O
disease O
progression O
( O
ADP O
) O
was O
defined O
as O
change O
of O
vitiligo O
disease O
activity O
score O
from O
4 O
+ O
to O
3 O
+ O
( O
time O
elapsed O
since O
last O
disease O
activity O
being O
more O
than O
6 O
weeks O
upto O
3 O
months O
) O
during O
the O
study O
period O
( O
6 O
months O
) O
. O
ADP O
was O
attained O
in O
21 O
patients O
in O
group O
1 B-STAT
and I-STAT
22 I-STAT
patients O
in O
group O
2 B-STAT
( O
84 O
% O
vs. O
88 O
% O
, O
p O
= O
1.00 O
) O
at O
the O
end O
of O
6 O
months O
. O
However O
, O
mean O
time O
to O
achieve O
ADP O
was O
significantly O
lower O
in O
group O
2 O
as O
compared O
to O
group O
1 O
( O
10.92 O
[ O
4.12 O
] O
weeks O
vs. O
13.90 O
[ O
3.92 O
] O
weeks O
, O
p O
= O
0.01 O
) O
. O
Extent O
of O
repigmentation O
, O
improvement O
in O
patient O
assessment O
score O
, O
vitiligo O
quality O
of O
life O
and O
clinical O
markers O
of O
disease O
activity O
were O
marginal O
and O
comparable O
in O
both O
groups O
. O
Cyclosporine O
leads O
to O
earlier O
disease O
stabilization O
in O
active O
vitiligo O
as O
compared O
to O
OMP O
. O
Although O
considered O
a O
rescue O
drug O
in O
dermatology O
, O
low O
dose O
cyclosporine O
can O
be O
an O
effective O
therapeutic O
alternative O
in O
vitiligo O
patients O
. O
Methylmalonic O
acidemia O
( O
MMA O
) O
is O
a O
lethal O
, O
severe O
heterogeneous O
disorder O
of O
methylmalonate O
and O
cobalamin O
( O
cbl O
; O
vitamin O
B12 O
) O
metabolism O
with O
poor O
prognosis O
. O
Two O
main O
forms O
of O
the O
disease O
have O
been O
identified O
, O
isolated O
methylmalonic O
acidurias O
and O
combined O
methylmalonic O
aciduria O
and O
homocystinuria O
, O
which O
is O
respectively O
caused O
by O
different O
gene O
mutations O
. O
Here O
, O
we O
review O
the O
improvement O
of O
pathogenesis O
, O
diagnosis O
and O
treatment O
in O
MMA B-LOC
. O
Importantly O
, O
the O
reported O
epidemiological O
data O
of O
MMA O
patients O
in O
China B-LOC
and O
the O
hot O
mutation O
sites O
in O
Chinese O
patients O
are O
listed O
, O
which O
will O
aid O
in O
improving O
healthcare O
of O
Chinese O
patients O
in O
the O
future O
. O
c.729_730insTT O
was O
the O
most O
common O
mutation O
in O
Chinese O
isolated O
MMA O
patients O
, O
while O
c.609G O
> O
A O
and O
c.658_660delAAG O
were O
in O
Chinese O
cblC O
type O
patients O
according O
to O
unrelated O
studies O
. O
The O
estimated O
newborn O
screening O
incidence B-EPI
was O
reported O
to O
be O
1:26,000 B-STAT
, O
1:3,920 B-STAT
, O
1:11,160 B-STAT
, O
1:6,032 B-STAT
respectively I-STAT
in I-STAT
Beijing B-LOC
and O
Shanghai B-LOC
, O
Shandong B-LOC
province I-LOC
, O
Taian B-LOC
district I-LOC
, O
and O
Henan B-LOC
province I-LOC
of I-LOC
China B-LOC
. O
Alternatively O
, O
when O
patients O
with O
suspected O
inherited O
metabolic O
diseases O
were O
used O
as O
the O
screened O
sample O
, O
the O
relatively O
high O
incidence B-EPI
0.3 B-STAT
% I-STAT
and O
1.32 O
% O
were O
respectively O
obtained O
in O
southern O
China B-LOC
and O
throughout O
all O
the O
provinces O
of O
mainland O
China B-LOC
and O
Macao B-LOC
with O
the O
exception O
of O
five O
provinces O
( O
Hainan B-LOC
, O
Neimenggu B-LOC
, O
Tibet B-LOC
, O
Ningxia B-LOC
, O
and O
Hong B-LOC
Kong I-LOC
) O
. O
The O
establishing O
of O
46 O
chromosomes O
as O
the O
normal O
complement O
in O
man O
and O
the O
report O
of O
the O
sex O
chromatin O
bodies O
in O
buccal O
smears O
were O
followed O
by O
reports O
of O
trisomies O
and O
other O
abnormal O
patterns O
of O
the O
X O
and O
Y O
chromosomes O
in O
Klinefelter O
's O
and O
Turner O
's O
syndromes O
. O
Abnormal O
autosomal O
complements O
were O
described O
in O
mongolism O
, O
in O
the O
E O
- O
trisomy O
syndrome O
, O
the O
D O
- O
trisomy O
syndrome O
, O
in O
the O
Sturge O
- O
Weber O
syndrome O
, O
Waldenstrom O
's O
macroglobulinemia O
, O
benign O
congenital O
hypotonia O
, O
atrial O
septal O
defect O
and O
in O
the O
schizoid O
personality O
. O
Certain O
of O
these O
conditions O
, O
as O
well O
as O
the O
O
oral O
- O
facial O
- O
digital O
O
syndrome O
, O
were O
also O
found O
to O
exist O
as O
partial O
trisomies O
. O
The O
mechanism O
of O
a O
trisomy O
is O
one O
of O
non O
- O
disjunction O
and O
of O
partial O
trisomy O
translocation O
or O
insertion O
. O
Two O
cases O
of O
the O
partial O
trisomy O
in O
the O
E O
group O
are O
described O
; O
these O
are O
of O
especial O
interest O
because O
of O
the O
familial O
incidence B-EPI
, O
longer O
survival O
and O
male O
sex O
occurrence B-EPI
, O
features O
which O
are O
rarely O
seen O
in O
the O
full O
E O
- O
trisomy O
syndrome O
. O
Background O
Consanguineous O
families O
have O
a O
relatively O
high O
prevalence B-EPI
of O
genetic O
disorders O
caused O
by O
bi O
- O
allelic O
mutations O
in O
recessive O
genes O
. O
This O
study O
aims O
to O
evaluate O
the O
effectiveness O
and O
efficiency O
of O
a O
consanguinity O
- O
based O
exome O
sequencing O
approach O
to O
capturing O
genetic O
mutations O
in O
inherited O
retinal O
dystrophy O
families O
with O
consanguineous O
marriages O
. O
Methods O
Ten O
unrelated O
consanguineous O
families O
with O
a O
proband O
affected O
by O
inherited O
retinal O
dystrophy O
were O
recruited O
in O
this O
study O
. O
All O
participants O
underwent O
comprehensive O
ophthalmic O
examinations O
. O
Whole O
exome O
sequencing O
was O
performed O
, O
followed O
by O
a O
homozygote O
- O
prior O
strategy O
to O
rapidly O
filter O
disease O
- O
causing O
mutations O
. O
Bioinformatic O
prediction O
of O
pathogenicity O
, O
Sanger O
sequencing O
and O
co O
- O
segregation O
analysis O
were O
carried O
out O
for O
further O
validation O
. O
Results O
In O
ten O
consanguineous O
families O
, O
a O
total O
of O
10 O
homozygous O
mutations O
in O
8 O
IRD O
genes O
were O
identified O
, O
including O
2 O
novel O
mutations O
, O
c.1654_1655delAG O
( O
p. O
R552Afs*5 O
) O
in O
gene O
FAM161A O
in O
a O
patient O
diagnosed O
with O
retinitis O
pigmentosa O
, O
and O
c.830 O
T O
> O
C O
( O
p. O
L277P O
) O
in O
gene O
CEP78 O
in O
a O
patient O
diagnosed O
with O
cone O
and O
rod O
dystrophy O
. O
Conclusion O
The O
genetic O
etiology O
in O
consanguineous O
families O
with O
IRD O
were O
successfully O
identified O
using O
consanguinity O
- O
based O
analysis O
of O
exome O
sequencing O
data O
, O
suggesting O
that O
this O
approach O
could O
provide O
complementary O
insights O
into O
genetic O
diagnoses O
in O
consanguineous O
families O
with O
variant O
genetic O
disorders O
. O
Charcot O
- O
Marie O
- O
Tooth O
( O
CMT O
) O
disease O
is O
a O
common O
inherited O
peripheral O
neuropathy O
. O
The O
CMT2 O
K O
axonal O
form O
is O
associated O
with O
GDAP1 O
dominant O
mutations O
, O
which O
according O
to O
the O
affected O
domain O
cause O
a O
gradient O
of O
severity O
. O
Indeed O
, O
the O
p. O
C240Y O
mutation O
, O
located O
within O
GDAP1 O
glutathione O
S O
- O
transferase O
( O
GST O
) O
domain O
and O
associated O
to O
a O
mitochondrial O
complex O
I O
defect O
, O
is O
related O
to O
a O
faster O
disease O
progression O
, O
compared O
to O
other O
mutations O
, O
such O
as O
the O
p. O
R120W O
located O
outside O
the O
GST O
domain O
. O
Here O
, O
we O
analysed O
the O
pathophysiology O
of O
six O
CMT2 O
K O
fibroblast O
cell O
lines O
, O
carrying O
either O
the O
p. O
C240Y O
or O
p. O
R120W O
mutations O
. O
We O
show O
that O
complex O
I O
deficiency O
leads O
to O
a O
redox O
potential O
alteration O
and O
a O
significant O
reduction O
of O
sirtuin O
1 O
( O
SIRT1 O
) O
expression O
, O
a O
major O
deacetylase O
sensitive O
to O
the O
cellular O
redox O
state O
, O
and O
NRF1 O
the O
downstream O
target O
of O
SIRT1 O
. O
In O
addition O
, O
we O
disclosed O
that O
the O
p. O
C240Y O
mutation O
is O
associated O
with O
a O
greater O
mitochondrial O
oxidative O
stress O
than O
the O
p. O
R120W O
mutation O
. O
Moreover O
, O
complex O
I O
activity O
is O
further O
restored O
in O
CMT2 O
K O
mutant O
cell O
lines O
exposed O
to O
resveratrol O
. O
Together O
, O
these O
results O
suggest O
that O
the O
reduction O
of O
oxidative O
stress O
may O
constitute O
a O
promising O
therapeutic O
strategy O
for O
CMT2K. O
Purpose O
Graves O
' O
orbitopathy O
( O
GO O
) O
is O
an O
inflammatory O
autoimmune O
disorder O
of O
the O
orbit O
and O
while O
the O
antiphospholipid O
antibodies O
( O
aPL O
) O
Abs O
were O
associated O
with O
the O
markers O
of O
inflammation O
in O
the O
antiphospholipid O
syndrome O
( O
APS O
) O
, O
there O
is O
no O
literature O
that O
investigate O
the O
presence O
of O
aPL O
Abs O
in O
GO O
. O
We O
analyzed O
the O
prevalence B-EPI
of O
aPL O
Abs O
and O
the O
differences O
between O
aPL O
( O
+ O
) O
and O
aPL O
( O
- O
) O
subgroups O
of O
GO O
patients O
. O
Methods O
Study O
included O
consecutive O
patients O
with O
GO O
( O
66 O
with O
Graves O
' O
( O
GD O
) O
, O
10 O
with O
Hashimoto O
( O
HD O
) O
, O
and O
8 O
were O
euthyroid O
) O
. O
Anticardiolipin O
( O
aCL O
) O
and O
anti O
- O
beta O
2glycoprotein O
I O
( O
aβ2gpI O
) O
Abs O
were O
measured O
by O
ELISA O
. O
Results O
aPL O
Abs O
were O
present O
in O
9/84 B-STAT
( O
10.71 O
% O
) O
patients O
. O
The O
IgM O
aβ2gpI O
Abs O
were O
present O
in O
8/66 B-STAT
and O
in O
1/10 B-STAT
patients O
with O
GD O
and O
HD O
. O
The O
IgG O
aCL O
Abs O
were O
present O
in O
one O
GD O
patient O
, O
and O
IgM O
aCL O
were O
present O
in O
3/66 B-STAT
GD O
and O
in O
1/10 B-STAT
patients O
with O
HD O
. O
In O
GD O
group O
, O
anti O
- O
Tg O
Abs O
were O
in O
positive O
correlation O
with O
aβ2gpI O
IgG O
( O
p O
= O
0.000 O
) O
and O
with O
anti O
- O
TPO O
Abs O
( O
p O
= O
0.016 O
) O
. O
In O
HD O
group O
, O
anti O
- O
Tg O
Abs O
were O
in O
positive O
correlation O
with O
IgM O
aCL O
( O
p O
= O
0.042 O
) O
, O
while O
anti O
- O
TPO O
Abs O
were O
in O
positive O
correlation O
with O
aβ2gpI O
IgM O
( O
p O
= O
0.014 O
) O
. O
Conclusion O
This O
study O
is O
the O
first O
report O
of O
the O
aPL O
Abs O
presence O
in O
GO O
patients O
. O
The O
anti O
- O
thyroid O
Abs O
were O
linked O
to O
aPL O
suggesting O
that O
their O
presence O
is O
not O
the O
sole O
consequence O
of O
hyperstimulation O
of O
autoreactive O
B O
- O
lymphocytes O
. O
Larger O
studies O
are O
necessary O
to O
confirm O
potential O
cause O
- O
effect O
relations O
. O
Since O
1984 O
, O
we O
have O
diagnosed O
at O
the O
La O
Paz O
University O
Hospital O
, O
Madrid B-LOC
, O
Spain B-LOC
, O
41 O
patients O
with O
hypoxanthine O
phosphoribosyltransferase O
( O
HPRT O
) O
activity O
deficiency O
. O
These O
patients O
belonged O
to O
34 O
families O
. O
We O
have O
also O
performed O
molecular O
and O
enzymatic O
diagnosis O
in O
three O
patients O
from O
India B-LOC
, O
one O
from O
Belgium B-LOC
, O
and O
three O
from O
Colombia B-LOC
. O
About O
1/3 B-STAT
of O
these O
patients O
were O
followed O
up O
at O
La O
Paz O
University O
Hospital O
at O
least O
every O
year O
. O
This O
fact O
has O
allowed O
us O
to O
examine O
the O
complete O
spectrum O
of O
HPRT O
deficiency O
as O
well O
as O
to O
perform O
a O
more O
accurate O
diagnosis O
and O
treatment O
. O
In O
the O
present O
review O
, O
we O
also O
summarized O
our O
studies O
on O
the O
basis O
of O
physiopathology O
of O
the O
neurological O
manifestation O
of O
Lesch O
Nyhan O
disease O
( O
LND O
) O
. O
Background O
Community O
- O
acquired O
pneumonia O
( O
CAP O
) O
is O
the O
major O
manifestation O
of O
Q O
fever O
, O
an O
emerging O
disease O
in O
French O
Guiana B-LOC
. O
Consequently O
, O
the O
empirical O
antibiotherapy O
used O
for O
the O
treatment O
of O
CAP O
combines O
doxycycline O
and O
the O
recommended O
amoxicillin O
. O
Our O
objectives O
were O
to O
estimate O
the O
prevalence B-EPI
of O
Q O
fever O
pneumonia O
and O
to O
build O
a O
prediction O
rule O
to O
identify O
patients O
with O
Q O
fever O
pneumonia O
for O
empirical O
antibiotic O
guidance O
. O
Methods O
A O
retrospective O
case O
- O
control O
study O
was O
conducted O
on O
inpatients O
admitted O
with O
CAP O
in O
the O
Department O
of O
Infectious O
Diseases O
of O
Cayenne O
Hospital O
from O
2004 O
to O
2007 O
. O
Serodiagnosis O
for O
Coxiella O
burnetii O
was O
performed O
for O
all O
patients O
. O
Risk O
factor O
analysis O
was O
performed O
using O
multivariate O
logistic O
regression O
, O
and O
a O
prognostic O
score O
was O
computed O
using O
bootstrap O
procedures O
. O
The O
score O
performance O
characteristics O
were O
used O
to O
choose O
the O
best O
prediction O
rule O
to O
identify O
patients O
with O
Q O
fever O
pneumonia O
. O
Results O
One O
hundred O
thirty O
- O
one O
patients O
with O
CAP O
were O
included O
and O
the O
Q O
fever O
pneumonia O
prevalence B-EPI
was O
24.4 O
% O
( O
95 O
% O
confidence O
interval O
[ O
CI O
] O
, O
17.1 O
- O
31.9 O
) O
. O
In O
multivariate O
analysis O
, O
male O
sex O
, O
middle O
age O
( O
age O
, O
30 O
- O
60 O
years O
) O
, O
headache O
, O
leukocyte O
count O
< O
10 B-STAT
× I-STAT
10(9)/L I-STAT
and O
C O
- O
reactive O
protein O
level O
> O
185 O
mg O
/ O
L O
were O
independently O
associated O
with O
Q O
fever O
pneumonia O
. O
Patients O
with O
a O
predictive O
score O
≤3 O
had O
a O
low O
risk O
of O
Q O
fever O
pneumonia O
with O
a O
negative O
predictive O
value O
of O
0.97 O
( O
95 O
% O
CI O
, O
.90 O
- O
1 O
) O
and O
a O
sensitivity O
of O
0.97 O
( O
95 O
% O
CI O
, O
.89 O
- O
1 O
) O
. O
Conclusions O
The O
prediction O
rule O
described O
here O
accurately O
identifies O
patients O
with O
low O
risk O
of O
Q O
fever O
pneumonia O
and O
may O
help O
physicians O
to O
make O
more O
rational O
decisions O
about O
the O
empirical O
use O
of O
antibiotherapy O
. O
Further O
prospective O
studies O
should O
be O
performed O
to O
validate O
this O
score O
. O
Introduction O
Neuromyelitis O
optica O
spectrum O
disorders O
( O
NMOSD O
) O
is O
an O
inflammatory O
and O
heterogeneous O
astrocyte O
disorder O
of O
the O
central O
nervous O
system O
with O
the O
characteristic O
of O
higher O
incidence B-EPI
in O
women O
and O
Asian O
people O
. O
Most O
patients O
with O
NMOSD O
have O
a O
course O
of O
recurrence O
and O
remission O
that O
is O
prone O
to O
cause O
paralysis O
and O
blindness O
. O
Several O
studies O
have O
confirmed O
the O
efficacy O
and O
promising O
prospect O
of O
mycophenolate O
mofetil O
( O
MMF O
) O
in O
the O
treatment O
of O
NMOSD O
. O
Yet O
its O
therapeutic O
effect O
and O
safety O
are O
controversial O
. O
Although O
there O
has O
been O
two O
published O
literature O
that O
is O
relevant O
to O
the O
topic O
of O
this O
study O
, O
both O
of O
them O
have O
certain O
defects O
, O
and O
they O
can O
only O
provide O
answers O
about O
the O
efficacy O
or O
safety O
of O
MMF O
in O
the O
treatment O
of O
NMOSD O
from O
partial O
perspectives O
or O
conclusions O
. O
This O
research O
aims O
to O
perform O
a O
direct O
and O
comprehensive O
systematic O
review O
and O
meta O
- O
analysis O
to O
evaluate O
MMF O
's O
effectiveness O
and O
safety O
in O
treating O
NMOSD O
. O
Methods O
and O
analysis O
This O
systematic O
review O
will O
cover O
all O
comparative O
researches O
, O
from O
randomised O
controlled O
trials O
to O
cohort O
studies O
, O
and O
case O
- O
control O
study O
. O
A O
relevant O
literature O
search O
will O
be O
conducted O
in O
PubMed O
, O
Web O
of O
Science O
, O
EMBASE O
, O
the O
Cochrane O
Library O
, O
China O
National O
Knowledge O
Infrastructure O
, O
Wanfang O
Database O
, O
China O
Science O
and O
Technology O
Journal O
Database O
and O
Chinese O
Biomedical O
Literature O
Database O
from O
their O
inception O
to O
31 O
June O
2020 O
. O
We O
will O
also O
search O
registers O
of O
clinical O
trials O
, O
potential O
grey O
literature O
and O
abstracts O
from O
conferences O
. O
There O
are O
no O
limits O
on O
language O
and O
publication O
status O
. O
The O
reporting O
quality O
and O
risk O
of O
bias O
will O
be O
assessed O
by O
two O
researchers O
independently O
. O
Expanded O
Disability O
Status O
Scales O
and O
annualised O
relapse O
rate O
will O
be O
evaluated O
as O
the O
primary O
outcome O
. O
The O
secondary O
outcomes O
will O
consist O
of O
the O
frequency O
and O
severity O
of O
adverse O
events O
, O
best O
- O
corrected O
visual O
acuity O
, O
relapse O
- O
free O
rate O
and O
time O
to O
the O
next O
attack O
. O
A O
meta O
- O
analysis O
will O
be O
performed O
using O
RevMan O
V.5.3 O
software O
provided O
by O
the O
Cochrane O
Collaboration O
and O
Stata O
V.12.0 O
. O
Ethics O
and O
dissemination O
Because O
the O
data O
used O
for O
this O
systematic O
review O
will O
be O
exclusively O
extracted O
from O
published O
studies O
, O
ethical O
approval O
and O
informed O
consent O
of O
patients O
will O
not O
be O
required O
. O
The O
systematic O
review O
will O
be O
published O
in O
a O
peer O
- O
reviewed O
journal O
, O
presented O
at O
conferences O
and O
will O
be O
shared O
on O
social O
media O
platforms O
. O
Prospero O
registration O
number O
CRD42020164179 O
. O
Purpose O
/ O
aim O
of O
the O
study O
: O
We O
report O
a O
rare O
case O
of O
autosomal O
dominant O
genetic O
syndrome O
O
Pfeiffer O
O
, O
which O
is O
part O
of O
the O
group O
of O
acrocephalosyndactyly O
, O
with O
an O
annual B-EPI
incidence I-EPI
< B-STAT
1/100,000 I-STAT
. O
Three O
forms O
are O
known O
. O
Type O
I O
is O
the O
less O
common O
form O
and O
it O
is O
characterized O
by O
moderate O
- O
severe O
mediofacial O
hypoplasia O
usually O
with O
normal O
cognitive O
development O
. O
Conversely O
, O
types O
2 O
and O
3 O
are O
more O
common O
and O
they O
are O
associated O
with O
more O
severe O
signs O
and O
complications O
with O
a O
more O
unfavorable O
prognosis O
. O
The O
type O
3 O
form O
due O
to O
the O
presence O
of O
a O
cloverleaf O
skull O
distinguishes O
type O
2 O
. O
Materials O
and O
methods O
: O
Thirty O
- O
eight O
- O
year O
- O
old O
primigravida O
was O
referred O
to O
our O
center O
, O
at O
28 O
weeks O
of O
gestation O
due O
to O
borderline O
ventriculomegaly O
, O
macrocrania O
, O
and O
a O
short O
femur O
. O
First O
trimester O
screening O
for O
chromosomopathies O
and O
CF O
- O
DNA O
was O
low O
risk O
; O
II O
trimester O
screening O
ultrasound O
showed O
the O
presence O
of O
O
short O
femur O
O
and O
macrocrania O
. O
Result O
: O
Our O
ultrasound O
evaluation O
, O
assisted O
by O
3D O
ultrasound O
, O
showed O
cloverleaf O
skull O
, O
turricephaly O
, O
moderate O
ventriculomegaly O
( O
13 O
mm O
) O
, O
hypertelorism O
and O
exophthalmos O
, O
low O
ear O
implantation O
, O
mild O
rhizomelia O
. O
Ultrasound O
depicts O
Pfeiffer O
syndrome O
or O
other O
acrocephalosyndactyly O
syndromes O
( O
Apert O
syndromes O
, O
Saethre O
- O
Chotzen O
) O
or O
other O
syndromic O
forms O
of O
craniosynostosis O
like O
Crouzon O
syndrome O
. O
The O
NGS O
panel O
for O
molecular O
analysis O
of O
genes O
involved O
in O
skeletal O
dysplasias O
showed O
the O
mutation O
of O
the O
FGFR2 O
gene O
, O
de O
novo O
. O
Conclusions O
: O
Using O
three O
- O
dimensional O
( O
3D O
) O
ultrasound O
, O
it O
is O
easier O
to O
distinguish O
rare O
syndromes O
characterized O
by O
facial O
dysmorphisms O
such O
as O
exophthalmos O
, O
mediofacial O
hypoplasia O
, O
and O
craniosynostosis O
. O
Genetic O
testing O
is O
used O
to O
optimise O
the O
management O
of O
inherited O
cardiovascular O
disorders O
that O
can O
cause O
sudden O
cardiac O
death O
. O
Yet O
more O
genotype O
- O
phenotype O
correlation O
studies O
from O
populations O
not O
ascertained O
on O
clinical O
symptoms O
or O
family O
history O
of O
disease O
are O
required O
to O
improve O
understanding O
of O
gene O
penetrance O
. O
We O
performed O
targeted O
sequencing O
of O
25 O
genes O
used O
routinely O
in O
clinical O
genetic O
testing O
for O
inherited O
cardiovascular O
disorders O
in O
a O
population O
of O
13,131 O
asymptomatic O
older O
individuals O
( O
mean O
age O
75 O
years O
) O
enrolled O
in O
the O
ASPREE O
trial O
. O
Participants O
had O
no O
prior O
history O
of O
cardiovascular O
disease O
events O
, O
dementia O
or O
physical O
disability O
at O
enrolment O
. O
Variants O
were O
classified O
following O
ACMG O
/ O
AMP O
standards O
. O
Sudden O
and O
rapid O
cardiac O
deaths O
were O
clinically O
adjudicated O
as O
ASPREE O
trial O
endpoints O
, O
and O
assessed O
during O
mean O
4.7 O
years O
of O
follow O
- O
up O
. O
In O
total O
, O
119 O
participants O
had O
pathogenic O
/ O
deleterious O
variants O
in O
one B-STAT
of I-STAT
the I-STAT
25 I-STAT
genes O
analysed O
( O
carrier O
rate O
of O
1 B-STAT
in I-STAT
110 B-STAT
or I-STAT
0.9 I-STAT
% I-STAT
) O
. O
Participants O
carried O
variants O
associated O
with O
hypertrophic O
cardiomyopathy O
( O
N O
= O
24 O
) O
, O
dilated O
cardiomyopathy O
( O
N O
= O
29 O
) O
, O
arrhythmogenic O
right O
- O
ventricular O
cardiomyopathy O
( O
N O
= O
22 O
) O
, O
catecholaminergic O
polymorphic O
ventricular O
tachycardia O
( O
N O
= O
4 O
) O
, O
aortopathies O
( O
N O
= O
1 B-STAT
) I-STAT
, O
and O
long O
- O
QT O
syndrome O
( O
N O
= O
39 O
) O
. O
Among O
119 O
carriers O
, O
two O
died O
from O
presumed O
sudden O
/ O
rapid O
cardiac O
deaths O
during O
follow O
- O
up O
( O
1.7 O
% O
) O
; O
both O
with O
pathogenic O
variants O
in O
long O
- O
QT O
syndrome O
genes O
( O
KCNQ1 O
, O
SCN5A O
) O
. O
Among O
non O
- O
carriers O
, O
the O
rate O
of O
sudden O
/ O
rapid O
cardiac O
deaths O
was O
significantly O
lower O
( O
0.08 B-STAT
% I-STAT
, O
11/12936 B-STAT
, O
p O
< O
0.001 O
) O
. O
Variants O
associated O
with O
inherited O
cardiovascular O
disorders O
are O
found O
in O
asymptomatic O
individuals O
aged O
70 O
years O
and O
older O
without O
a O
history O
of O
cardiovascular O
disease O
. O
Adrenal O
insufficiency O
may O
result O
from O
a O
wide O
variety O
of O
congenital O
or O
acquired O
disorders O
of O
hypothalamus O
, O
pituitary O
, O
or O
adrenal O
cortex O
. O
Destruction O
or O
dysfunction O
of O
the O
adrenal O
cortex O
is O
the O
cause O
of O
primary O
adrenal O
insufficiency O
, O
while O
secondary O
adrenal O
insufficiency O
is O
a O
result O
of O
pituitary O
or O
hypothalamic O
disease O
. O
Timely O
diagnosis O
and O
clinical O
management O
of O
adrenal O
insufficiency O
are O
critical O
to O
prevent O
morbidity O
and O
mortality O
. O
This O
review O
summarizes O
the O
etiologies O
, O
presentation O
, O
and O
diagnosis O
of O
adrenal O
insufficiency O
utilizing O
different O
dynamic O
hormone O
testing O
and O
describes O
current O
treatment O
recommendations O
and O
new O
therapies O
. O
Objective O
To O
determine O
the O
prevalence B-EPI
of O
Barth O
syndrome O
in O
the O
pediatric O
population O
. O
Study O
design O
Data O
were O
collected O
from O
the O
Barth O
Syndrome O
Foundation O
Registry O
and O
relevant O
literature O
. O
With O
the O
advent O
of O
genetic O
testing O
and O
whole O
- O
exome O
sequencing O
, O
a O
multipronged O
Bayesian O
analysis O
was O
used O
to O
estimate O
the O
prevalence B-EPI
of O
Barth O
syndrome O
based O
on O
published O
data O
on O
the O
incidence B-EPI
and O
prevalence B-EPI
of O
cardiomyopathy O
and O
neutropenia O
, O
and O
the O
respective O
subpopulations O
of O
patients O
with O
Barth O
syndrome O
indicated O
in O
these O
publications O
. O
Results O
Based O
on O
7 O
published O
studies O
of O
cardiomyopathy O
and O
2 O
published O
studies O
of O
neutropenia O
, O
the O
estimated B-EPI
prevalence I-EPI
of O
Barth O
syndrome O
is O
approximately O
1 B-STAT
case I-STAT
per I-STAT
million I-STAT
male I-STAT
population O
. O
This O
contrasts O
with O
99 O
cases O
in O
the O
Barth O
Syndrome O
Foundation O
Registry O
, O
58 O
of O
which O
indicate O
a O
US B-LOC
location O
, O
and O
only O
230 O
- O
250 O
cases O
known O
worldwide B-LOC
. O
Conclusions O
It O
appears O
that O
Barth O
syndrome O
is O
greatly O
underdiagnosed O
. O
There O
is O
a O
need O
for O
better O
education O
and O
awareness O
of O
this O
rare O
disease O
to O
move O
toward O
early O
diagnosis O
and O
treatment O
. O
Ogilvie O
syndrome O
is O
a O
clinical O
condition O
in O
which O
there O
is O
a O
colorectal O
distention O
in O
the O
absence O
of O
mechanical O
obstacles O
. O
Early O
diagnosis O
and O
appropriate O
therapy O
significantly O
reduce O
mortality O
. O
The O
incidence B-EPI
of O
this O
is O
not O
known O
. O
This O
paper O
presents O
the O
course O
of O
diagnosis O
and O
treatment O
, O
both O
conservative O
and O
operational O
, O
of O
an O
82 O
year O
old O
patient O
with O
pulmonary O
embolism O
, O
burdened O
with O
coronary O
artery O
disease O
, O
hypertension O
, O
heart O
failure O
and O
chronic O
kidney O
failure O
, O
in O
which O
the O
hospital O
diagnosed O
Ogilvie O
syndrome O
. O
OBJECTIVES O
: O
To O
examine O
the O
incidence B-EPI
, O
mortality O
, O
and O
health O
care O
use O
related O
to O
neonatal O
herpes O
simplex O
virus O
( O
HSV O
) O
infection O
. O
METHODS O
: O
A O
retrospective O
longitudinal O
cohort O
study O
using O
a O
multistate O
Medicaid O
claims O
database O
. O
We O
identified O
neonates O
hospitalized O
with O
HSV O
infection O
from O
2009 O
to O
2015 O
by O
using O
discharge O
diagnosis O
codes O
and O
managed O
them O
for O
6 O
months O
after O
discharge O
. O
Incidence B-EPI
rates O
were O
corrected O
for O
the O
imperfect O
sensitivity O
and O
specificity O
of O
thediagnosis O
codes O
for O
identifying O
HSV O
infection O
. O
RESULTS O
: O
Of O
2 O
107 O
124 O
births O
from O
2009 O
to O
2015 O
, O
900 O
neonates O
were O
identified O
with O
HSV O
infection O
, O
with O
a O
corrected O
incidence B-EPI
rate O
of O
4.5 O
( O
95 O
% O
confidence O
interval O
[ O
CI O
] O
: O
4.2 B-STAT
- I-STAT
4.8 I-STAT
) I-STAT
per I-STAT
10 I-STAT
000 I-STAT
births I-STAT
. O
The O
yearly O
disease O
incidence B-EPI
increased O
by O
56 O
% O
, O
from O
3.4 O
( O
95 O
% O
CI O
: O
2.8 B-STAT
- I-STAT
4.2 I-STAT
) I-STAT
per I-STAT
10 I-STAT
000 I-STAT
births I-STAT
( O
or O
1 B-STAT
in I-STAT
2941 I-STAT
births I-STAT
) O
in O
2009 O
to O
5.3 O
( O
95 O
% O
CI O
: O
4.6 B-STAT
- I-STAT
6.1 I-STAT
) I-STAT
per I-STAT
10 I-STAT
000 I-STAT
births I-STAT
( O
or O
1 B-STAT
in I-STAT
1886 I-STAT
births I-STAT
) O
in O
2015 O
( O
P O
< O
.001 O
) O
. O
Of O
the O
900 O
neonates O
with O
HSV O
infection O
, O
54 B-STAT
( O
6.0 O
% O
[ O
95 O
% O
CI O
: O
4.4%-7.6 O
% O
] O
) O
died O
during O
the O
index O
hospitalization O
; O
there O
was O
no O
increase O
in O
the O
yearly O
mortality O
rate O
. O
Of O
the O
692 B-STAT
( O
81.2 O
% O
) O
infants O
with O
follow O
- O
up O
data O
, O
316 B-STAT
( O
45.7 O
% O
) O
had O
an O
emergency O
department O
visit O
, O
and O
112 B-STAT
( O
16.2 O
% O
) O
had O
a O
hospital O
readmission O
. O
Total O
payments O
at O
6 O
months O
amounted O
to O
$ O
60 O
620 O
431 O
, O
a O
median O
of O
$ O
87 B-STAT
602 I-STAT
per I-STAT
case I-STAT
of I-STAT
neonatal O
HSV O
infection O
. O
CONCLUSIONS O
: O
We O
observed O
an O
increase O
in O
neonatal O
HSV O
infection O
incidence B-EPI
over O
a O
recent O
7 O
- O
year O
period O
in O
a O
Medicaid O
population O
. O
Associated O
health O
care O
use O
and O
payments O
were O
substantial O
. O
Public O
health O
interventions O
targeting O
disease O
prevention O
and O
early O
diagnosis O
are O
needed O
. O
Despite O
the O
prevalence B-EPI
of O
preterm O
brain O
injury O
, O
there O
are O
no O
established O
neuroprotective O
strategies O
to O
prevent O
or O
alleviate O
mild O
- O
to O
- O
moderate O
inflammation O
- O
related O
brain O
injury O
. O
Perinatal O
infection O
and O
inflammation O
have O
been O
shown O
to O
trigger O
acute O
neuroinflammation O
, O
including O
proinflammatory O
cytokine O
release O
and O
gliosis O
, O
which O
are O
associated O
with O
acute O
and O
chronic O
disturbances O
in O
brain O
cell O
survival O
and O
maturation O
. O
These O
findings O
suggest O
the O
hypothesis O
that O
the O
inhibition O
of O
peripheral O
immune O
responses O
following O
infection O
or O
nonspecific O
inflammation O
may O
be O
a O
therapeutic O
strategy O
to O
reduce O
the O
associated O
brain O
injury O
and O
neurobehavioral O
deficits O
. O
This O
review O
provides O
an O
overview O
of O
the O
neonatal O
immunity O
, O
neuroinflammation O
, O
and O
mechanisms O
of O
inflammation O
- O
related O
brain O
injury O
in O
preterm O
infants O
and O
explores O
the O
safety O
and O
efficacy O
of O
anti O
- O
inflammatory O
agents O
as O
potentially O
neurotherapeutics O
. O
Inferior O
vena O
cava O
( O
IVC O
) O
agenesis O
is O
a O
rare O
congenital O
abnormality O
affecting O
the O
infrarenal O
segment O
, O
the O
suprarenal O
or O
the O
whole O
of O
the O
IVC O
. O
It O
has O
an O
estimated B-EPI
prevalence I-EPI
of O
up O
to O
1 B-STAT
% O
in O
the O
general O
population O
that O
can O
rise B-STAT
to O
8.7 O
% O
when O
abnormalities O
of O
the O
left O
renal O
vein O
are O
considered O
. O
Most O
IVC O
malformations O
are O
asymptomatic O
but O
may O
be O
associated O
with O
nonspecific O
symptoms O
or O
present O
as O
deep O
vein O
thrombosis O
( O
DVT O
) O
. O
Up B-STAT
to O
5 O
% O
of O
young O
individuals O
under O
30 O
years O
of O
age O
with O
unprovoked O
DVT O
are O
found O
to O
have O
this O
condition O
. O
Regarding O
the O
treatment O
of O
IVC O
agenesis O
- O
associated O
DVT O
, O
there O
are O
no O
standard O
guidelines O
. O
Treatment O
is O
directed O
towards O
preventing O
thrombosis O
or O
its O
recurrence O
. O
Low O
molecular O
weight O
heparin O
and O
oral O
anticoagulation O
medication O
, O
in O
particular O
vitamin O
K O
antagonists O
( O
VKAs O
) O
are O
the O
mainstay O
of O
therapy O
. O
Given O
the O
high O
risk O
of O
DVT O
recurrence O
in O
these O
patients O
, O
oral O
anticoagulation O
therapy O
is O
suggested O
to O
be O
pursued O
indefinitely O
. O
As O
far O
as O
we O
know O
, O
this O
is O
the O
first O
case O
reporting O
the O
use O
of O
a O
direct O
factor O
Xa O
inhibitor O
in O
IVC O
agenesis O
- O
associated O
DVT O
. O
Given O
VKA O
monitoring O
limitations O
, O
the O
use O
of O
a O
direct O
Xa O
inhibitor O
could O
be O
an O
alternative O
in O
young O
individuals O
with O
anatomical O
defects O
without O
thrombophilia O
, O
but O
further O
studies O
will O
be O
needed O
to O
confirm O
its O
efficacy O
and O
safety O
. O
LEARNING O
POINTS O
: O
Up O
to O
5 B-STAT
% O
of O
young O
individuals O
under O
30 O
years O
of O
age O
with O
unprovoked O
deep O
vein O
thrombosis O
( O
DVT O
) O
are O
found O
to O
have O
this O
condition O
. O
Therefore O
, O
these O
types O
of O
anomalies O
should O
be O
actively O
looked O
for O
, O
particularly O
in O
young O
patients O
with O
DVT.Treatment O
with O
low O
molecular O
weight O
heparin O
or O
oral O
anticoagulation O
medication O
is O
the O
mainstay O
of O
therapy O
, O
directed O
towards O
preventing O
thrombosis O
or O
its O
recurrence O
. O
A O
direct O
factor O
Xa O
inhibitor O
could O
be O
a O
possible O
alternative O
to O
vitamin O
K O
antagonists O
in O
these O
patients O
, O
despite O
the O
lack O
of O
clinical O
evidence O
supporting O
its O
use O
at O
the O
moment O
. O
BACKGROUND O
: O
Lesch O
- O
Nyhan O
syndrome O
( O
LNS O
) O
is O
a O
congenital O
X O
- O
linked O
recessive O
neurogenetic O
disorder O
caused O
by O
mutations O
in O
the O
hypoxanthine O
- O
guanine O
phosphoribosyltransferase O
( O
HPRT O
) O
gene O
. O
The O
main O
clinical O
manifestation O
includes O
hyperuricemia O
, O
juvenile O
- O
onset O
gouty O
arthritis O
, O
and O
neurological O
developmental O
disorders O
. O
Studies O
have O
reported O
more O
than O
400 O
HPRT O
gene O
mutation O
sites O
, O
but O
the O
incidence B-EPI
of O
LNS O
in O
the O
Chinese O
population O
is O
extremely O
low O
. O
METHODS O
: O
Here O
we O
report O
a O
16 O
- O
year O
- O
old O
male O
patient O
who O
suffered O
neurological O
dysfunction O
at O
an O
early O
age O
and O
gouty O
arthritis O
in O
his O
youth O
. O
RESULTS O
: O
No O
activity O
of O
the O
HPRT O
enzyme O
was O
detected O
in O
the O
erythrocytes O
. O
Furthermore O
, O
we O
found O
a O
mutation O
on O
exon O
3 O
of O
the O
HPRT O
gene O
in O
the O
patient O
and O
his O
mother O
( O
exon O
3 O
: O
c.143G O
> O
A O
) O
, O
which O
resulted O
in O
arginine O
to O
histidine O
( O
p. O
R48H O
) O
substitution O
in O
the O
encoded O
protein O
. O
The O
same O
mutation O
was O
reported O
in O
several O
European O
families O
, O
but O
was O
found O
for O
the O
first O
time O
in O
a O
Chinese O
family O
. O
CONCLUSIONS O
: O
Clinicians O
in O
China B-LOC
have O
poor O
experience O
in O
diagnosing O
LNS O
cases O
due O
to O
the O
low O
incidence B-EPI
in O
China B-LOC
. O
Therefore O
, O
LNS O
screening O
for O
infants O
or O
adolescents O
with O
hyperuricemia O
, O
gouty O
arthritis O
, O
and O
neurological O
dysfunction O
should O
be O
performed O
. O
Objectives O
Few O
studies O
have O
investigated O
the O
prognostic O
factors O
for O
idiopathic O
inflammatory O
myopathy O
- O
associated O
interstitial O
lung O
disease O
( O
IIM O
- O
ILD O
) O
across O
different O
clinical O
/ O
serological O
phenotypes O
. O
Methods O
We O
conducted O
a O
retrospective O
analysis O
of O
patients O
diagnosed O
with O
IIM O
between O
January O
2012 O
and O
December O
2017 O
. O
Results O
Of O
the O
760 O
IIM O
cases O
registered O
, O
679 O
adult O
cases O
were O
included O
in O
this O
study O
. O
ILD O
was O
present O
in O
508 O
cases O
, O
and O
the O
presence O
of O
ILD O
in O
the O
clinically O
amyopathic O
DM B-LOC
, O
DM O
and O
PM O
groups O
was O
92.7 O
, O
73.6 O
and O
55.1 O
% O
, O
respectively O
( O
P O
< O
0.01 O
) O
. O
The O
prevalence B-EPI
of O
ILD O
in O
the O
anti O
- O
synthetase O
antibody O
( O
ASA)+-IIM O
group O
was O
higher O
than O
that O
in O
ASA O
-- O
IIM O
group O
( O
95.2 O
vs O
72.4 O
% O
, O
P O
< O
0.01 O
) O
; O
no O
such O
difference O
was O
found O
between O
the O
anti O
- O
histidyl O
- O
tRNA O
synthetase O
( O
Jo-1)+-IIM O
and O
Jo-1 O
- O
ASA+-IIM O
groups O
( O
93.0 O
vs O
98.5 O
% O
, O
P O
> O
0.05 O
) O
. O
The O
prevalence B-EPI
of O
ILD O
in O
the O
melanoma O
differentiation O
- O
associated O
protein-5 O
( O
MDA-5)+-IIM O
group O
was O
higher O
than O
that O
in O
MDA-5 O
- O
-IIM O
group O
( O
97.8 O
vs O
72.1 O
% O
, O
P O
< O
0.01 O
) O
. O
Among O
adults O
with O
IIM O
, O
men O
with O
concurrent O
ILD O
, O
who O
were O
older O
than O
50 O
years O
, O
were O
most O
likely O
to O
die O
. O
No O
significant O
difference O
was O
found O
in O
the O
all O
- O
cause O
mortality O
rates O
between O
DM O
- O
ILD O
and O
clinically O
amyopathic O
DM O
- O
ILD O
groups O
( O
33.3 O
vs O
23 O
% O
, O
P O
> O
0.05 O
) O
, O
although O
both O
were O
higher O
than O
that O
in O
PM O
group O
( O
13.2 O
% O
, O
P O
= O
0.01 O
and O
P O
< O
0.05 O
, O
respectively O
) O
. O
No O
difference O
was O
found O
in O
the O
all O
- O
cause O
mortality O
rates O
between O
MDA5 O
- O
ASA O
-- O
IM O
- O
ILD O
and O
MDA5 O
- O
ASA+-IM O
- O
ILD O
groups O
( O
17.2 O
vs O
12.8 O
% O
, O
P O
> O
0.05 O
) O
, O
and O
both O
were O
lower O
than O
that O
in O
MDA5+ASA O
-- O
IM O
- O
ILD O
group O
( O
33.7 O
% O
, O
P O
< O
0.05 O
) O
. O
Conclusion O
The O
prevalence B-EPI
of O
ILD O
in O
IIM O
and O
the O
prognosis O
of O
IIM O
- O
ILD O
patients O
may O
vary O
depending O
on O
the O
statuses O
of O
the O
ASA O
and O
MDA-5 O
antibodies O
. O
Background O
: O
Little O
is O
known O
about O
the O
surgical O
conditions O
affecting O
the O
pediatric O
population O
in O
low O
- O
income O
countries O
. O
In O
this O
article O
we O
describe O
the O
epidemiology O
of O
pediatric O
surgical O
diseases O
observed O
in O
Mutoyi B-LOC
hospital O
, O
a O
first O
- O
level O
hospital O
in O
Burundi B-LOC
. O
Methods O
and O
Findings O
: O
We O
retrospectively O
reviewed O
the O
records O
of O
all O
children O
( O
0 O
- O
14 O
years O
) O
admitted O
to O
the O
Surgery O
ward O
from O
January O
2017 O
to O
December O
2017 O
. O
We O
also O
reviewed O
the O
records O
of O
all O
the O
patients O
admitted O
to O
the O
Neonatology B-LOC
ward O
in O
2017 O
and O
among O
them O
we O
selected O
the O
ones O
in O
which O
a O
surgical O
diagnosis O
was O
present O
. O
Five O
hundred O
twenty O
- O
eight O
children O
were O
admitted O
to O
the O
surgical O
ward O
during O
the O
study O
period O
. O
The O
most O
common O
conditions O
requiring O
hospitalization O
were O
abscesses O
( O
29.09 O
% O
) O
, O
fractures O
( O
13.59 O
% O
) O
, O
osteomyelitis O
( O
9.76 O
% O
) O
, O
burns O
( O
5.40 O
% O
) O
and O
head O
injuries O
( O
4.36 O
% O
) O
. O
The O
average O
length O
of O
stay O
was O
16 O
days O
. O
Fifty O
- O
six O
newborns O
were O
admitted O
to O
the O
Neonatology B-LOC
ward O
for O
a O
surgical O
condition O
; O
29 O
% O
of O
them O
had O
an O
abscess O
. O
Conclusions O
: O
Conditions O
requiring O
surgical O
care O
are O
frequent O
in O
Burundian O
children O
and O
have O
a O
completely O
different O
spectrum O
from O
the O
western O
ones O
. O
This O
is O
due O
on O
one O
side O
to O
an O
under O
- O
diagnosis O
of O
certain O
conditions O
caused O
by O
the O
lack O
of O
diagnostic O
tools O
and O
on O
the O
other O
to O
the O
living O
conditions O
of O
the O
population O
. O
This O
difference O
should O
lead O
to O
intervention O
plans O
tailored O
on O
the O
actual O
necessities O
of O
the O
country O
and O
not O
on O
the O
western O
ones O
. O
Introduction O
Tinea O
capitis O
is O
the O
most O
common O
form O
of O
dermatophytosis O
among O
children O
, O
contributing O
significantly O
to O
the O
global O
burden O
of O
skin O
and O
hair O
infections O
. O
However O
, O
an O
accurate O
account O
of O
its O
burden O
in O
Africa B-LOC
, O
where O
most O
cases O
are O
thought O
to O
occur O
, O
is O
lacking O
. O
We O
aim O
to O
systematically O
evaluate O
the O
burden O
, O
aetiology O
and O
epidemiological O
trend O
of O
tinea O
capitis O
among O
children O
over O
a O
30 O
- O
year O
period O
in O
Africa B-LOC
. O
Methods O
and O
analysis O
A O
systematic O
review O
will O
be O
conducted O
using O
Embase O
, O
PubMed O
, O
African O
Journals O
Online O
, O
Web O
of O
Science O
and O
the O
Cochrane O
Library O
of O
Systematic O
Review O
. O
These O
resources O
will O
be O
used O
to O
identify O
studies O
published O
between O
1990 O
and O
December O
2020 O
, O
which O
report O
the O
prevalence B-EPI
, O
aetiology O
and O
trend O
of O
tinea O
capitis O
among O
children O
younger O
than O
18 O
years O
in O
Africa B-LOC
. O
Articles O
in O
English O
and O
French O
will O
be O
considered O
. O
Two O
independent O
reviewers O
will O
screen O
the O
articles O
for O
eligibility O
, O
and O
any O
discrepancies O
will O
be O
resolved O
by O
discussion O
and O
consensus O
between O
the O
authors O
. O
Methodological O
quality O
of O
all O
studies O
will O
be O
assessed O
and O
critically O
appraised O
. O
We O
will O
perform O
a O
metaregression O
to O
assess O
the O
impact O
of O
study O
characteristics O
on O
heterogeneity O
and O
also O
to O
correct O
the O
meta O
- O
analytical O
estimates O
for O
biases O
. O
A O
qualitative O
synthesis O
will O
be O
performed O
, O
and O
STATA O
V.16.0 O
software O
will O
be O
used O
to O
estimate O
the O
pooled B-EPI
prevalence I-EPI
and O
aetiology O
of O
tinea O
capitis O
. O
The O
Mann O
- O
Kendall O
trend O
test O
will O
be O
use O
to O
evaluate O
the O
trend O
in O
the O
prevalence B-EPI
of O
tinea O
capitis O
over O
the O
study O
period O
. O
Ethics O
and O
dissemination O
Ethical O
approval O
from O
an O
institutional O
review O
board O
or O
research O
ethics O
committee O
is O
not O
required O
for O
this O
systematic O
review O
and O
meta O
- O
analysis O
. O
The O
results O
will O
be O
published O
in O
a O
peer O
- O
reviewed O
journal O
and O
presented O
in O
conferences O
. O
Background O
: O
Previous O
research O
has O
suggested O
that O
vigorous O
physical O
activity O
( O
VPA O
) O
during O
adolescence O
and O
early O
adulthood O
is O
associated O
with O
ALS O
. O
The O
National O
ALS O
Registry O
( O
Registry O
) O
collects O
physical O
activity O
data O
from O
persons O
with O
ALS O
. O
Objective O
: O
To O
examine O
the O
association O
between O
vigorous O
VPA O
and O
early O
onset O
ALS O
, O
defined O
as O
a O
diagnosis O
before O
age O
60 O
, O
among O
patients O
enrolled O
in O
the O
Registry O
. O
VPA O
was O
defined O
as O
engaging O
in O
dynamic O
exercise O
for O
at O
least O
10 O
minutes O
in O
a O
session O
that O
caused O
heavy O
sweating O
or O
large O
increases O
in O
breathing O
or O
heart O
rate O
. O
Methods O
: O
A O
cross O
- O
sectional O
study O
was O
conducted O
of O
5463 O
ALS O
patients O
with O
VPA O
history O
and O
956 O
ALS O
patients O
who O
never O
engaged O
in O
VPA O
. O
Patient O
characteristics O
were O
collected O
via O
online O
surveys O
in O
the O
following O
areas O
: O
demographic O
, O
lifetime O
VPA O
history O
, O
and O
initial O
onset O
of O
symptoms O
. O
General O
linear O
modeling O
was O
used O
to O
estimate O
mean O
age O
of O
diagnosis O
and O
to O
compute O
95 O
% O
confidence O
intervals O
. O
Results O
: O
Patients O
who O
reported O
engaging O
in O
VPA O
at O
least O
moderately O
( O
three O
times O
a O
week O
) O
during O
early O
adulthood O
were O
more O
likely O
to O
have O
an O
ALS O
diagnosis O
earlier O
compared O
to O
patients O
who O
did O
not O
( O
p O
< O
0.0001 O
) O
. O
After O
controlling O
for O
year O
of O
birth O
, O
statistically O
significant O
associations O
between O
those O
reporting O
VPA O
at O
age O
15 O
- O
24 O
and O
25 O
- O
34 O
and O
diagnosis O
of O
ALS O
earlier O
( O
p O
= O
0.0009 O
, O
p O
= O
0.0144 O
respectively O
) O
. O
Conclusion O
: O
Patients O
with O
ALS O
who O
had O
a O
history O
of O
VPA O
before O
age O
35 O
, O
were O
significantly O
more O
likely O
to O
be O
diagnosed O
with O
ALS O
before O
age O
60 O
compared O
to O
patients O
with O
ALS O
who O
never O
engaged O
vigorously O
. O
More O
research O
is O
needed O
in O
the O
relationship O
between O
VPA O
and O
early O
onset O
ALS O
. O
Despite O
numerous O
studies O
in O
the O
field O
of O
congenital O
adrenal O
hyperplasia O
( O
CAH O
) O
due O
to O
21 O
- O
hydroxylase O
deficiency O
, O
some O
clinical O
variability O
of O
the O
presentation O
and O
discrepancies O
in O
the O
genotype O
/ O
phenotype O
correlation O
are O
still O
unexplained O
. O
Some O
, O
but O
not O
all O
, O
discordant O
phenotypes O
caused O
by O
mutations O
with O
known O
enzyme O
activity O
have O
been O
explained O
by O
in O
silico O
structural O
changes O
in O
the O
21 O
- O
hydroxylase O
protein O
. O
The O
incidence B-EPI
of O
P30L O
mutation O
varies O
in O
different O
populations O
and O
is O
most O
frequently O
found O
in O
several O
Central O
and O
Southeast O
European O
countries O
as O
well O
as O
Mexico B-LOC
. O
Patients O
carrying O
P30L O
mutation O
present O
predominantly O
as O
non O
- O
classical O
CAH O
; O
however O
, O
simple O
virilizing O
forms O
are O
found O
in O
up O
to O
50 B-STAT
% O
of O
patients O
. O
Taking O
into O
consideration O
the O
residual O
21 O
- O
hydroxulase O
activity O
present O
with O
P30L O
mutation O
this O
is O
unexpected O
. O
Different O
mechanisms O
for O
increased O
androgenization O
in O
patients O
carrying O
P30L O
mutation O
have O
been O
proposed O
including O
influence O
of O
different O
residues O
, O
accompanying O
promotor O
allele O
variability O
or O
mutations O
, O
and O
individual O
androgene O
sensitivity O
. O
Early O
diagnosis O
of O
patients O
who O
would O
present O
with O
SV O
is O
important O
in O
order O
to O
improve O
outcome O
. O
Outcome O
studies O
of O
CAH O
have O
confirmed O
the O
uniqueness O
of O
this O
mutation O
such O
as O
difficulties O
in O
phenotype O
classification O
, O
different O
fertility O
, O
growth O
, O
and O
psychologic O
issues O
in O
comparison O
with O
other O
genotypes O
. O
Additional O
studies O
of O
P30L O
mutation O
are O
warranted O
. O
Background O
Charcot O
- O
Marie O
- O
Tooth O
disease O
type O
1A O
( O
CMT1A O
) O
is O
the O
most O
common O
form O
of O
hereditary O
neuropathy O
. O
Objective O
To O
investigate O
the O
prevalence B-EPI
and O
characteristics O
of O
pain O
in O
patients O
with O
CMT1A. O
Methods O
Nineteen O
patients O
with O
a O
diagnosis O
of O
CMT1A O
were O
evaluated O
between O
September O
2018 O
and O
October O
2019 O
, O
and O
other O
causes O
of O
neuropathy O
were O
ruled O
out O
. O
The O
following O
tools O
were O
used O
for O
the O
pain O
assessment O
: O
neurological O
assessment O
, O
LANSS O
, O
DN4 O
, O
clinical O
evaluation O
, O
VAS O
, O
CMTNS2 O
and O
SF-36 O
. O
Statistical O
analysis O
was O
performed O
using O
prevalence B-EPI
analysis O
, O
t O
test O
, O
chi O
- O
square O
test O
and O
Spearman O
's O
rho O
. O
Results O
The O
prevalence B-EPI
of O
pain O
was O
84.2 O
% O
in O
the O
sample O
of O
this O
study O
, O
with O
moderate O
intensity O
and O
nociceptive O
characteristics O
according O
to O
the O
LANSS O
scale O
( O
75 O
% O
) O
and O
clinical O
evaluation O
( O
50 O
% O
) O
, O
but O
differing O
from O
DN4 O
, O
which O
found O
neuropathic O
pain O
in O
the O
majority O
of O
the O
patients O
( O
56.2 O
% O
) O
. O
Mixed O
pain O
was O
also O
observed O
in O
43.7 O
% O
of O
the O
patients O
, O
according O
to O
clinical O
criteria O
. O
There O
was O
a O
statistically O
significant O
correlation O
between O
pain O
intensity O
and O
SF-36 O
, O
thus O
demonstrating O
that O
the O
lower O
the O
pain O
was O
, O
the O
lower O
the O
impairment O
was O
, O
in O
all O
domains O
. O
Conclusion O
Pain O
is O
a O
prevalent B-EPI
and O
important O
symptom O
in O
CMT1A O
, O
with O
moderate O
intensity O
and O
nociceptive O
characteristics O
according O
to O
two O
tools O
, O
but O
neuropathic O
pain O
is O
also O
present O
, O
and O
there O
may O
even O
be O
a O
mixed O
pattern O
of O
pain O
. O
The O
correlation O
of O
the O
pain O
with O
SF-36 O
suggests O
that O
pain O
relief O
could O
provide O
improvements O
to O
the O
quality O
of O
life O
of O
these O
individuals O
. O
Auditory O
neuropathy O
spectrum O
disorder O
( O
ANSD O
) O
refers O
to O
a O
range O
of O
hearing O
impairments O
characterized O
by O
deteriorated O
speech O
perception O
, O
despite O
relatively O
preserved O
pure O
- O
tone O
detection O
thresholds O
. O
Affected O
individuals O
usually O
present O
with O
abnormal O
auditory O
brainstem O
responses O
( O
ABRs O
) O
, O
but O
normal O
otoacoustic O
emissions O
( O
OAEs O
) O
. O
These O
electrophysiological O
characteristics O
have O
led O
to O
the O
hypothesis O
that O
ANSD O
may O
be O
caused O
by O
various O
dysfunctions O
at O
the O
cochlear O
inner O
hair O
cell O
( O
IHC O
) O
and O
spiral O
ganglion O
neuron O
( O
SGN O
) O
levels O
, O
while O
the O
activity O
of O
outer O
hair O
cells O
( O
OHCs O
) O
is O
preserved O
, O
resulting O
in O
discrepancies O
between O
pure O
- O
tone O
and O
speech O
comprehension O
thresholds O
. O
The O
exact O
prevalence B-EPI
of O
ANSD O
remains O
unknown O
; O
clinical O
findings O
show O
a O
large O
variability O
among O
subjects O
with O
hearing O
impairment O
ranging O
from O
mild O
to O
profound O
hearing O
loss O
. O
A O
wide O
range O
of O
prenatal O
and O
postnatal O
etiologies O
have O
been O
proposed O
. O
The O
study O
of O
genetics O
and O
of O
the O
implicated O
sites O
of O
lesion O
correlated O
with O
clinical O
findings O
have O
also O
led O
to O
a O
better O
understanding O
of O
the O
molecular O
mechanisms O
underlying O
the O
various O
forms O
of O
ANSD O
, O
and O
may O
guide O
clinicians O
in O
better O
screening O
, O
assessment O
and O
treatment O
of O
ANSD O
patients O
. O
Besides O
OAEs O
and O
ABRs O
, O
audiological O
assessment O
includes O
stapedial O
reflex O
measurements O
, O
supraliminal O
psychoacoustic O
tests O
, O
electrocochleography O
( O
ECochG O
) O
, O
auditory O
steady O
- O
state O
responses O
( O
ASSRs O
) O
and O
cortical O
auditory O
evoked O
potentials O
( O
CAEPs O
) O
. O
Hearing O
aids O
are O
indicated O
in O
the O
treatment O
of O
ANSD O
with O
mild O
to O
moderate O
hearing O
loss O
, O
whereas O
cochlear O
implantation O
is O
the O
first O
choice O
of O
treatment O
in O
case O
of O
profound O
hearing O
loss O
, O
especially O
in O
case O
of O
IHC O
presynaptic O
disorders O
, O
or O
in O
case O
of O
poor O
auditory O
outcomes O
with O
conventional O
hearing O
aids O
. O
Thyroid O
cancer O
( O
TC O
) O
represents O
a O
worldwide B-LOC
problem O
, O
the O
consistent O
growth O
of O
the O
incidence B-EPI
increment O
issues O
about O
management O
of O
risk O
factors O
and O
curative O
treatment O
. O
Updated O
statistical O
data O
are O
not O
complete O
in O
the O
North B-LOC
East I-LOC
region O
of O
Romania B-LOC
and O
need O
to O
be O
improved O
. O
Therefore O
, O
through O
this O
study O
, O
we O
aim O
to O
renew O
the O
existing O
data O
on O
thyroid O
cancer O
. O
We O
conducted O
a O
retrospective O
study O
covering O
a O
period O
of O
10 O
years O
. O
Data O
were O
collected O
from O
a O
hospital O
information O
system O
( O
InfoWorld O
) O
between O
2009 O
and O
2019 O
. O
Patients O
' O
age O
groups O
were O
stratified O
in O
relation O
with O
the O
age O
at O
the O
moment O
of O
the O
Chernobyl B-LOC
event O
. O
A O
database O
was O
obtained O
( O
Microsoft O
Excel O
) O
and O
statistical O
correlations O
were O
applied O
. O
In O
the O
studied O
period O
, O
1159 O
patients O
were O
diagnosed O
: O
968 O
females O
and O
191 O
males O
, O
distributed O
by O
region O
, O
with O
the O
highest O
addressability O
in O
Iasi B-LOC
( O
529 O
) O
, O
followed O
by O
neighboring O
counties O
. O
Age O
distribution O
displayed O
that O
most O
of O
the O
thyroid O
cancers O
were O
in O
the O
range O
4060 O
years O
old O
( O
50.94 O
% O
) O
, O
followed O
by O
60 O
- O
80 O
years O
old O
( O
32.41 O
% O
) O
. O
Most O
patients O
were O
diagnosed O
with O
papillary O
carcinoma O
63.10 O
% O
, O
then O
follicular O
14.7 O
% O
, O
medullary O
6.74 O
% O
and O
undifferentiated O
1.02 B-STAT
% I-STAT
. O
Romania B-LOC
was O
in O
the O
vicinity O
of O
the O
radioactive O
cloud O
at O
Chernobyl B-LOC
fallout O
, O
so O
we O
must O
deliberate O
whether O
the O
increased O
incidence B-EPI
of O
thyroid O
cancer O
in O
the O
age O
group O
40 O
- O
60 O
years O
is O
associated O
with O
radiogenicity O
( O
iodine O
131 O
) O
given O
the O
fact O
that O
over O
has O
35 O
years O
and O
the O
half O
- O
life O
of O
other O
radioisotopes O
like O
Caesium-137 O
and O
Strontium O
-90 O
is O
completed O
. O
The O
field O
of O
Cardio O
- O
oncology O
is O
rapidly O
growing O
with O
significant O
advances O
in O
research O
leading O
to O
better O
understanding O
of O
the O
underlying O
pathogenesis O
with O
implications O
in O
the O
diagnosis O
and O
management O
of O
cancer O
- O
related O
cardiomyopathy O
. O
Parallel O
to O
advancement O
in O
cardio O
- O
oncology O
is O
an O
increased O
awareness O
of O
the O
incidence B-EPI
of O
congestive O
heart O
failure O
and O
cardiomyopathy O
associated O
with O
malignancy O
. O
While O
specific O
cardiotoxic O
profiles O
exist O
for O
certain O
chemotherapeutic O
agents O
, O
there O
is O
increasing O
evidence O
of O
unexpected O
cardiotoxic O
side O
effects O
of O
some O
therapeutic O
modalities O
, O
combination O
chemo- O
and O
radiotherapy O
with O
large O
analyses O
identifying O
a O
strong O
association O
between O
malignancy O
and O
Takotsubo O
cardiomyopathy O
. O
Takotsubo O
Cardiomyopathy O
, O
also O
known O
as O
O
broken O
- O
heart O
O
syndrome O
or O
stress O
cardiomyopathy O
, O
is O
characterized O
by O
transient O
and O
reversible O
, O
regional O
or O
global O
, O
myocardial O
dysfunction O
without O
inciting O
ischemic O
perfusion O
defect O
from O
obstructive O
coronary O
artery O
disease O
. O
While O
direct O
causative O
pathophysiologic O
mechanisms O
continue O
to O
be O
investigated O
, O
much O
of O
the O
postulated O
pathways O
center O
on O
the O
high O
emotional O
and O
physical O
burdens O
of O
cancer O
and O
the O
related O
emotional O
stress O
associated O
with O
the O
diagnosis O
of O
cancer O
as O
well O
as O
the O
corporal O
effects O
of O
anti O
- O
neoplastic O
therapies O
, O
radiation O
, O
and O
oncologic O
surgery O
. O
In O
this O
manuscript O
we O
review O
the O
most O
current O
data O
in O
this O
rapidly O
emerging O
field O
highlighting O
the O
epidemiology O
, O
the O
postulated O
pathogenetic O
mechanisms O
as O
well O
as O
the O
current O
guidelines O
by O
major O
societies O
addressing O
malignancy O
-associated O
heart O
failure O
and O
cardiomyopathy O
, O
a O
rather O
complex O
disease O
entity O
with O
high O
morbidity O
and O
mortality O
. O
Mutations O
in O
the O
genes O
for O
extracellular O
matrix O
( O
ECM O
) O
components O
cause O
a O
wide O
range O
of O
genetic O
connective O
tissues O
disorders O
throughout O
the O
body O
. O
The O
elucidation O
of O
mutations O
and O
their O
correlation O
with O
pathology O
has O
been O
instrumental O
in O
understanding O
the O
roles O
of O
many O
ECM O
components O
. O
The O
pathological O
consequences O
of O
ECM O
protein O
mutations O
depend O
on O
its O
tissue O
distribution O
, O
tissue O
function O
, O
and O
on O
the O
nature O
of O
the O
mutation O
. O
The O
prevalent B-EPI
paradigm O
for O
the O
molecular O
pathology O
has O
been O
that O
there O
are O
two O
global O
mechanisms O
. O
First O
, O
mutations O
that O
reduce O
the O
production O
of O
ECM O
proteins O
impair O
matrix O
integrity O
largely O
due O
to O
quantitative O
ECM O
defects O
. O
Second O
, O
mutations O
altering O
protein O
structure O
may O
reduce O
protein O
secretion O
but O
also O
introduce O
dominant O
negative O
effects O
in O
ECM O
formation O
, O
structure O
and/or O
stability O
. O
Recent O
studies O
show O
that O
endoplasmic O
reticulum O
( O
ER O
) O
stress O
, O
caused O
by O
mutant O
misfolded O
ECM O
proteins O
, O
makes O
a O
significant O
contribution O
to O
the O
pathophysiology O
. O
This O
suggests O
that O
targeting O
ER O
- O
stress O
may O
offer O
a O
new O
therapeutic O
strategy O
in O
a O
range O
of O
ECM O
disorders O
caused O
by O
protein O
misfolding O
mutations O
. O
Anat O
Rec O
, O
2019 O
. O
© O
2019 O
The O
Authors O
. O
The O
Anatomical O
Record O
published O
by O
Wiley O
Periodicals O
, O
Inc. O
on O
behalf O
of O
American O
Association O
of O
Anatomists O
. O
E. O
histolytica O
is O
an O
intestinal O
parasite O
that O
causes O
asymptomatic O
infection O
mostly O
; O
however O
, O
it O
may O
also O
cause O
amoebic O
dysentery O
and O
liver O
abscess O
. O
Molecular O
identification O
is O
required O
in O
epidemiological O
studies O
due O
to O
the O
presence O
of O
morphologically O
identical O
nonpathogenic O
species O
. O
Therefore O
, O
this O
study O
was O
conducted O
to O
first O
evaluate O
the O
prevalence B-EPI
rate O
of O
E. O
histolytica O
among O
symptomatic O
individuals O
of O
Erbil B-LOC
city O
, O
and O
to O
investigate O
the O
genetic O
diversity O
of O
the O
parasite O
in O
a O
limited O
geographic O
area O
. O
Accordingly O
, O
a O
total O
of O
2026 O
samples O
were O
examined O
microscopically O
, O
and O
confirmed O
by O
nested O
PCR O
for O
18s O
rRNA O
gene O
. O
The O
results O
showed O
that O
the O
prevalence B-EPI
rate O
of O
E. O
histolytica O
was O
1.97 O
% O
( O
40 O
samples O
) O
among O
symptomatic O
patients O
. O
The O
SREHP O
gene O
was O
used O
as O
a O
marker O
to O
show O
the O
genetic O
polymorphism O
of O
E. O
histolytica O
; O
however O
, O
to O
compare O
the O
genetic O
diversity O
of O
symptomatic O
with O
asymptomatic O
isolates O
, O
57 O
asymptomatic O
samples O
were O
obtained O
from O
our O
previous O
study O
. O
The O
amplified O
products O
of O
the O
SREHP O
gene O
were O
digested O
by O
AluI O
endonuclease O
, O
and O
DNA O
banding O
patterns O
were O
analysed O
. O
Results O
showed O
29 O
different O
DNA O
patterns O
among O
the O
97 O
symptomatic O
and O
asymptomatic O
samples O
, O
62 O
of O
which O
shared O
similar O
DNA O
patterns O
. O
However O
, O
8 O
different O
DNA O
patterns O
were O
observed O
among O
asymptomatic O
samples O
, O
whereas O
15 O
distinct O
patterns O
were O
observed O
among O
symptomatic O
isolates O
. O
In O
conclusion O
, O
this O
study O
found O
that O
the O
prevalence B-EPI
rate O
of O
E. O
histolytica O
was O
relatively O
low O
; O
relatively O
high O
genetic O
diversity O
was O
observed O
in O
a O
restricted O
endemic O
area O
; O
with O
higher O
rates O
of O
variability O
in O
symptomatic O
rather O
than O
in O
asymptomatic O
isolates O
, O
indicating O
a O
possible O
correlation O
between O
the O
genotype O
of O
E. O
histolytica O
and O
their O
clinical O
outcome O
. O
Background O
Nonclassical O
congenital O
adrenal O
hyperplasia O
due O
to O
21 O
- O
hydroxylase O
deficiency O
is O
caused O
by O
mutations O
in O
the O
active O
21 O
- O
hydroxylase O
gene O
( O
CYP21A2 O
) O
. O
The O
clinical O
symptoms O
can O
vary O
greatly O
. O
To O
date O
, O
no O
systematic O
studies O
have O
been O
undertaken O
in O
Germany B-LOC
. O
Aims O
Description O
of O
the O
phenotype O
, O
evaluation O
of O
the O
diagnostics O
and O
genotype O
- O
phenotype O
correlation O
PATIENTS O
AND O
METHODOLOGY O
: O
Retrospective O
analysis O
of O
the O
data O
of O
134 O
patients O
( O
age O
range O
0.1 O
- O
18.6 O
years O
) O
in O
a O
multicentre O
study O
covering O
10 O
paediatric O
endocrinology O
centres O
in O
Bavaria B-LOC
and O
Baden B-LOC
- I-LOC
Württemberg I-LOC
. O
The O
data O
was O
gathered O
on O
site O
from O
the O
medical O
records O
. O
Two O
hundred O
and O
thirty O
- O
three O
alleles O
with O
a O
mutation O
of O
the O
CYP21A2 O
gene O
were O
identified O
in O
126 O
patients O
. O
A O
genotype O
- O
phenotype O
correlation O
of O
the O
mutation O
findings O
was O
undertaken O
( O
C1 O
, O
severe O
/ O
mild O
; O
C2 O
, O
mild O
/ O
mild O
) O
. O
Individuals O
with O
a O
heterozygous O
mutation O
of O
the O
CYP21A2 O
were O
also O
included O
( O
C3 O
) O
. O
The O
data O
was O
collected O
with O
the O
approval O
of O
the O
ethics O
committee O
of O
the O
University O
Hospital O
of O
Erlangen O
during O
the O
period O
of O
2014 O
and O
2015 O
. O
RESULTS O
( O
MW O
± O
SD O
): O
One O
hundred O
and O
seventeen O
out O
of O
134 O
patients O
( O
115 O
f O
, O
29 O
m O
) O
were O
symptomatic O
. O
The O
chronological O
age O
( O
CA O
) O
at O
diagnosis O
was O
7.1 O
± O
4.4 O
years O
. O
The O
most O
frequent O
symptom O
( O
73.5 O
% O
) O
was O
premature O
pubarche O
. O
The O
height O
- O
SDS O
on O
diagnosis O
was O
0.8 O
± O
1.3 O
and O
the O
BMI O
- O
SDS O
was O
0.8 O
± O
1.2 O
. O
Bone O
age O
( O
BA O
) O
was O
ascertained O
in O
82.9 O
% O
of O
the O
symptomatic O
patients O
. O
The O
difference O
between O
BA O
and O
CA O
was O
1.9 O
± O
1.4 O
years O
. O
Basal O
17OHP O
concentrations O
were O
14.5 O
± O
19.1 O
ng O
/ O
ml O
( O
18 O
patients O
< O
2 O
ng O
/ O
ml O
) O
. O
In O
total O
, O
58.1 O
% O
mild O
and O
34.7 O
% O
severe O
mutations O
were O
found O
. O
The O
most O
common O
mutation O
was O
p. O
Val281Leu O
( O
39.1 O
% O
) O
; O
65.8 O
% O
of O
the O
patients O
could O
be O
allocated O
to O
group O
C1 O
. O
No O
phenotypical O
differences O
were O
found O
between O
the O
3 O
mutation O
groups O
. O
The O
17OHP O
levels O
( O
basal O
and O
after O
ACTH O
) O
in O
the O
standard O
ACTH O
stimulation O
test O
were O
highest O
in O
group O
C1 O
and O
also O
significantly O
higher O
in O
group O
C2 O
as O
in O
C3 O
, O
the O
ACTH O
- O
stimulated O
cortisol O
levels O
( O
ng O
/ O
ml O
) O
were O
significantly O
lower O
in O
groups O
C1 O
( O
192.1 O
± O
62.5 O
) O
and O
C2 O
( O
218 O
± O
50 O
) O
than O
in O
C3 O
( O
297.3 O
± O
98.7 O
) O
. O
Conclusion O
Most O
of O
the O
patients O
have O
symptoms O
of O
mild O
androgenisation O
. O
Male O
patients O
are O
underdiagnosed O
. O
Diagnostics O
are O
not O
standardised O
. O
Differences O
between O
the O
types O
of O
mutations O
are O
found O
in O
the O
hormone O
concentrations O
but O
not O
in O
phenotype O
. O
We O
speculate O
that O
further O
, O
as O
yet O
not O
clearly O
defined O
, O
factors O
are O
responsible O
for O
the O
development O
of O
the O
respective O
phenotypes O
. O
Standardized O
screening O
assessments O
and O
sex O
differences O
in O
autism O
spectrum O
disorder O
( O
ASD O
) O
are O
still O
under O
- O
explored O
in O
Poland B-LOC
. O
This O
study O
investigated O
the O
differences O
between O
Polish O
ASD O
females O
and O
males O
based O
on O
the O
responses O
provided O
by O
parents O
/ O
caregivers O
to O
a O
Polish O
adaptation O
of O
the O
Social O
Communication O
Questionnaire O
, O
SCQ O
Lifetime O
and O
SCQ O
Current O
. O
The O
study O
included O
90 O
ASD O
participants O
from O
Mental O
Health O
Services O
and O
Autism O
Clinics O
in O
Poland B-LOC
with O
no O
intellectual O
disability O
and O
no O
profound O
communication O
difficulties O
. O
Parents O
provided O
information O
on O
the O
SCQ O
items O
which O
were O
compared O
under O
three O
domains O
of O
the O
Autism O
Diagnostic O
Interview O
- O
Revised O
( O
ADI O
- O
R O
) O
. O
Four O
SCQ O
items O
with O
the O
examples O
were O
investigated O
. O
No O
significant O
differences O
were O
found O
between O
the O
two O
sexes O
in O
the O
three O
domains O
. O
The O
repetitive O
use O
of O
objects O
declined O
with O
age O
in O
ASD O
males O
. O
Although O
the O
findings O
of O
the O
present O
study O
did O
not O
reveal O
substantial O
gender O
biases O
in O
the O
Polish O
adaptation O
of O
the O
SCQ O
, O
it O
is O
necessary O
to O
take O
into O
account O
potential O
gender O
differences O
in O
the O
clinical O
presentation O
of O
ASD O
and O
in O
the O
adaptation O
of O
screening O
and O
diagnostic O
tools O
. O
Congenital O
disorders O
of O
glycosylation O
( O
CDG O
) O
are O
rare O
diseases O
with O
variable O
phenotypes O
and O
severity O
. O
Immunological O
involvement O
remains O
a O
largely O
uncharted O
topic O
in O
CDG O
, O
mainly O
due O
to O
lack O
of O
robust O
data O
. O
To O
better O
characterize O
immune O
- O
related O
manifestations O
' O
prevalence B-EPI
, O
relevance O
, O
and O
quality O
- O
of O
- O
life O
( O
QoL O
) O
impact O
, O
we O
developed O
electronic O
questionnaires O
targeting O
( O
1 O
) O
CDG O
patients O
and O
( O
2 O
) O
the O
general O
O
healthy O
O
population O
. O
Two O
- O
hundred O
and O
nine O
CDG O
patients O
/ O
caregivers O
and O
349 O
healthy O
participants O
were O
included O
in O
this O
study O
. O
PMM2 O
- O
CDG O
was O
the O
most O
represented O
CDG O
( O
n O
= O
122/209 B-STAT
) O
. O
About O
half O
of O
these O
participants O
( O
n O
= O
65/122 B-STAT
) O
described O
relevant O
infections O
with O
a O
noteworthy O
prevalence B-EPI
of O
those O
affecting O
the O
gastrointestinal O
tract O
( O
GI O
) O
( O
63.1 O
% O
, O
n O
= O
41/65 B-STAT
) O
. O
Infection O
burden O
and O
QoL O
impact O
were O
shown O
as O
infections O
correlated O
with O
more O
severe O
clinical O
phenotypes O
and O
with O
a O
set O
of O
relevant O
non O
- O
immune O
PMM2 O
- O
CDG O
signs O
. O
Autoimmune O
diseases O
had O
only O
a O
marginal O
presence O
in O
PMM2 O
- O
CDG O
( O
2.5 O
% O
, O
n O
= O
3/122 B-STAT
) O
, O
all O
being O
GI O
- O
related O
. O
Allergy O
prevalence B-EPI
was O
also O
low O
in O
PMM2 O
- O
CDG O
( O
33 O
% O
, O
n O
= O
41/122 B-STAT
) O
except O
for O
food O
allergies O
( O
26.8 O
% O
, O
n O
= O
11/41 B-STAT
, O
of O
PMM2 O
- O
CDG O
and O
10.8 O
% O
, O
n O
= O
17/158 B-STAT
, O
of O
controls O
) O
. O
High O
vaccination O
compliance O
with O
greater O
perceived O
ineffectiveness O
( O
28.3 O
% O
, O
n O
= O
17/60 B-STAT
) O
and O
more O
severe O
adverse O
reactions O
were O
described O
in O
PMM2 O
- O
CDG O
. O
This O
people O
- O
centric O
approach O
not O
only O
confirmed O
literature O
findings O
, O
but O
created O
new O
insights O
into O
immunological O
involvement O
in O
CDG O
, O
namely O
by O
highlighting O
the O
possible O
link O
between O
the O
immune O
and O
GI O
systems O
in O
PMM2 O
- O
CDG O
. O
Finally O
, O
our O
results O
emphasized O
the O
importance O
of O
patient O
/ O
caregiver O
knowledge O
and O
raised O
several O
red O
flags O
about O
immunological O
management O
. O
Isolated O
cleft O
palate O
( O
CPO O
) O
is O
the O
rarest O
form O
of O
oral O
clefting O
. O
The O
incidence B-EPI
of O
CPO O
varies O
substantially O
by O
geography O
from O
1.3 B-STAT
to I-STAT
25.3 I-STAT
per I-STAT
10,000 I-STAT
live I-STAT
births I-STAT
, O
with O
the O
highest O
rates O
in O
British B-LOC
Columbia I-LOC
, O
Canada B-LOC
and O
the O
lowest O
rates O
in O
Nigeria B-LOC
, O
Africa B-LOC
. O
Stratified O
by O
ethnicity O
/ O
race O
, O
the O
highest O
rates O
of O
CPO O
are O
observed O
in O
non O
- O
Hispanic O
Whites O
and O
the O
lowest O
in O
Africans O
; O
nevertheless O
, O
rates O
of O
CPO O
are O
consistently O
higher O
in O
females O
compared O
to O
males O
. O
Approximately O
fifty O
percent O
of O
cases O
born O
with O
cleft O
palate O
occur O
as O
part O
of O
a O
known O
genetic O
syndrome O
or O
with O
another O
malformation O
( O
e.g. O
, O
congenital O
heart O
defects O
) O
and O
the O
other O
half O
occur O
as O
solitary O
defects O
, O
referred O
to O
often O
as O
non O
- O
syndromic O
clefts O
. O
The O
etiology O
of O
CPO O
is O
multifactorial O
involving O
genetic O
and O
environmental O
risk O
factors O
. O
Several O
animal O
models O
have O
yielded O
insight O
into O
the O
molecular O
pathways O
responsible O
for O
proper O
closure O
of O
the O
palate O
, O
including O
the O
BMP O
, O
TGF O
- O
β O
, O
and O
SHH O
signaling O
pathways O
. O
In O
terms O
of O
environmental O
exposures O
, O
only O
maternal O
tobacco O
smoke O
has O
been O
found O
to O
be O
strongly O
associated O
with O
CPO O
. O
Some O
studies O
have O
suggested O
that O
maternal O
glucocorticoid O
exposure O
may O
also O
be O
important O
. O
Clearly O
, O
there O
is O
a O
need O
for O
larger O
epidemiologic O
studies O
to O
further O
investigate O
both O
genetic O
and O
environmental O
risk O
factors O
and O
gene O
- O
environment O
interactions O
. O
In O
terms O
of O
treatment O
, O
there O
is O
a O
need O
for O
long O
- O
term O
comprehensive O
care O
including O
surgical O
, O
dental O
and O
speech O
pathology O
. O
Overall O
, O
five O
main O
themes O
emerge O
as O
critical O
in O
advancing O
research O
: O
( O
1 O
) O
monitoring O
of O
the O
occurrence B-EPI
of O
CPO O
( O
capacity O
building O
) O
; O
( O
2 O
) O
detailed O
phenotyping O
of O
the O
severity O
( O
biology O
) O
; O
( O
3 O
) O
understanding O
of O
the O
genetic O
and O
environmental O
risk O
factors O
( O
primary O
prevention O
) O
; O
( O
4 O
) O
access O
to O
early O
detection O
and O
multidisciplinary O
treatment O
( O
clinical O
services O
) O
; O
and O
( O
5 O
) O
understanding O
predictors O
of O
recurrence O
and O
possible O
interventions O
among O
families O
with O
a O
child O
with O
CPO O
( O
secondary O
prevention O
) O
. O
Introduction O
Psoriatic O
arthritis O
( O
PsA O
) O
is O
a O
chronic O
immune O
- O
mediated O
inflammatory O
spondyloarthropathy O
associated O
with O
psoriasis O
. O
PsA O
is O
frequently O
associated O
with O
metabolic O
disorders O
including O
, O
obesity O
, O
metabolic O
syndrome O
, O
and O
diabetes O
mellitus O
( O
DM O
) O
. O
Type O
2 O
DM O
is O
among O
the O
most O
common O
metabolic O
disorders O
, O
with O
a O
prevalence B-EPI
ranging O
from O
2.4 B-STAT
to O
14.8 O
% O
in O
the O
general O
population O
. O
Methods O
We O
conducted O
a O
narrative O
review O
of O
the O
English O
- O
language O
studies O
from O
January O
1989 O
to O
September O
2019 O
investigating O
the O
risk O
of O
type O
2 O
DM O
in O
patients O
with O
PsA O
, O
the O
pathogenic O
mechanism O
linking O
DM O
to O
PsA O
, O
and O
the O
effects O
on O
insulin O
sensitivity O
exerted O
by O
systemic O
therapies O
for O
PsA. O
Results O
The O
prevalence B-EPI
of O
type O
2 O
DM O
in O
patients O
with O
PsA O
ranges O
from O
6.1 B-STAT
to O
20.2 O
% O
, O
generally O
higher O
when O
compared O
to O
the O
general O
population O
. O
The O
higher O
risk O
of O
DM O
is O
reported O
in O
women O
with O
more O
severe O
forms O
of O
PsA. O
Elevated O
serum O
levels O
of O
adipokines O
, O
including O
TNF O
- O
α O
, O
which O
inhibits O
the O
autophosphorylation O
of O
the O
insulin O
receptor O
and O
suppresses O
the O
expression O
of O
glucose O
transporter O
4 O
, O
favor O
insulin O
resistance O
and O
could O
partially O
explain O
the O
association O
between O
PsA O
and O
DM O
. O
Moreover O
, O
adiponectin O
and O
omentin O
, O
with O
insulin O
- O
sensitizing O
and O
anti O
- O
atherogenic O
properties O
, O
are O
decreased O
in O
patients O
with O
PsA. O
Some O
of O
the O
treatments O
for O
PsA O
could O
affect O
the O
glucose O
homeostasis O
. O
Systemic O
corticosteroids O
are O
known O
to O
impair O
insulin O
resistance O
, O
whereas O
apremilast O
( O
phosphodiesterase O
type O
4 O
inhibitor O
) O
and O
TNF O
- O
α O
inhibitors O
could O
exert O
neutral O
effect O
or O
reduce O
the O
insulin O
- O
resistance O
. O
The O
role O
of O
IL-17 O
or O
IL-23 O
inhibitors O
has O
been O
marginally O
investigated O
. O
Conclusions O
Patients O
affected O
by O
PsA O
have O
a O
higher O
prevalence B-EPI
of O
type O
2 O
DM O
compared O
with O
the O
general O
population O
. O
The O
mechanism O
linking O
PsA O
with O
DM O
has O
not O
been O
completely O
clarified O
, O
but O
some O
of O
the O
principal O
mediators O
could O
be O
TNF O
- O
α O
and O
adipokine O
, O
especially O
adiponectin O
and O
omentin O
. O
Apremilast O
and O
TNF O
- O
α O
inhibitor O
may O
have O
a O
favorable O
effect O
and O
could O
be O
safely O
used O
in O
patients O
with O
DM O
. O
The O
life O
span O
of O
patients O
with O
primary O
and O
secondary O
immunodeficiency O
is O
increasing O
due O
to O
recent O
improvements O
in O
therapeutic O
strategies O
. O
While O
the O
incidence B-EPI
of O
primary O
immunodeficiencies O
( O
PIDs O
) O
is O
1:10,000 B-STAT
births I-STAT
, I-STAT
that O
of O
secondary O
immunodeficiencies O
are O
more O
common O
and O
are O
associated O
with O
posttransplantation O
immune O
dysfunction O
, O
with O
immunosuppressive O
medication O
for O
human O
immunodeficiency O
virus O
or O
with O
human O
T O
- O
cell O
lymphotropic O
virus O
infection O
. O
After O
infection O
, O
malignancy O
is O
the O
most O
prevalent B-EPI
cause O
of O
death O
in O
both O
children O
and O
adults O
with O
( O
PIDs O
) O
. O
PIDs O
more O
often O
associated O
with O
cancer O
include O
common O
variable O
immunodeficiency O
( O
CVID O
) O
, O
Wiskott O
- O
Aldrich O
syndrome O
, O
ataxia O
- O
telangiectasia O
, O
and O
severe O
combined O
immunodeficiency O
. O
This O
suggests O
that O
a O
protective O
immune O
response O
against O
both O
infectious O
non O
- O
self-(pathogens O
) O
and O
malignant O
self O
- O
challenges O
( O
cancer O
) O
exists O
. O
The O
increased O
incidence B-EPI
of O
cancer O
has O
been O
attributed O
to O
defective O
elimination O
of O
altered O
or O
O
transformed O
O
cells O
and/or O
defective O
immunity O
towards O
cancer O
cells O
. O
The O
concept O
of O
aberrant O
immune O
surveillance O
occurring O
in O
PIDs O
is O
supported O
by O
evidence O
in O
mice O
and O
from O
patients O
undergoing O
immunosuppression O
after O
transplantation O
. O
Here O
, O
we O
discuss O
the O
importance O
of O
PID O
defects O
in O
the O
development O
of O
malignancies O
and O
the O
current O
limitations O
associated O
with O
molecular O
pathogenesis O
of O
these O
diseases O
and O
emphasize O
the O
need O
for O
further O
knowledge O
of O
how O
specific O
mutations O
can O
modulate O
the O
immune O
system O
to O
alter O
immunosurveillance O
and O
thereby O
play O
a O
key O
role O
in O
the O
etiology O
of O
malignancies O
in O
PID O
patients O
. O
Purpose O
of O
review O
The O
aim O
was O
to O
review O
evidence O
about O
diabetes O
secondary O
to O
hereditary O
pancreatitis O
, O
seeking O
novel O
diagnostic O
and O
treatment O
features O
. O
Recent O
findings O
Hereditary O
pancreatitis O
( O
HP O
) O
is O
an O
autosomal O
dominant O
condition O
, O
characterized O
by O
recurrent O
episodes O
of O
acute O
pancreatitis O
, O
progression O
to O
fibrosis O
, O
and O
chronic O
pancreatitis O
. O
Clinical O
presentation O
includes O
diabetes O
of O
the O
exocrine O
pancreas O
( O
DEP O
) O
. O
HP O
prevalence B-EPI
ranges O
from O
0.3 B-STAT
to I-STAT
0.57 I-STAT
per I-STAT
100,000 I-STAT
people I-STAT
, O
with O
up O
to O
80 B-STAT
% O
of O
these O
develop O
DEP O
. O
This O
condition O
often O
requires O
specific O
interventions O
: O
with O
regard O
to O
metabolic O
control O
, O
metformin O
is O
the O
first O
choice O
for O
those O
with O
mild O
DEP O
, O
and O
for O
those O
in O
advanced O
disease O
, O
insulin O
is O
considered O
the O
first O
- O
line O
therapy O
. O
Insulin O
analogues O
and O
insulin O
pump O
therapy O
are O
preferred O
due O
to O
the O
brittle O
glycemic O
pattern O
and O
risk O
of O
hypoglycemia O
. O
In O
case O
of O
exocrine O
insufficiency O
, O
pancreatic O
enzyme O
replacement O
therapy O
is O
recommended O
. O
Pancreatic O
polypeptide O
administration O
is O
a O
promising O
novel O
treatment O
feature O
. O
DEP O
due O
to O
HP O
appears O
to O
be O
a O
misdiagnosed O
condition O
. O
The O
requirement O
of O
specific O
management O
demonstrates O
the O
importance O
of O
this O
matter O
; O
therefore O
, O
appropriate O
recognition O
and O
classification O
are O
important O
. O
Background O
. O
Vitamin O
C O
, O
E O
, O
D O
, O
A O
, O
zinc O
are O
considered O
to O
be O
essential O
in O
preventing O
and O
treating O
of O
acute O
respiratory O
infections O
( O
ARI O
) O
including O
COVID-19 O
. O
Methods O
. O
We O
reviewed O
published O
studies O
evaluating O
the O
potential O
roles O
of O
these O
vitamin O
and O
zinc O
for O
ARIs O
and O
COVID-19 O
using O
Medline O
database O
, O
medRxiv O
, O
and O
bibliographic O
references O
. O
Results O
. O
Vitamins O
C O
, O
D O
, O
and O
E O
did O
not O
reduce O
incidence B-EPI
of O
common O
cold O
in O
general O
, O
but O
vitamin O
C O
reduced O
by O
half O
in O
population O
with O
physical O
and O
environment O
stresses O
. O
Vitamins O
C O
and O
E O
shortened O
duration O
and O
reduced O
severity O
of O
common O
cold O
. O
A O
large O
- O
dose O
vitamin O
A O
had O
no O
effect O
on O
recovery O
from O
pneumonia O
. O
Zinc O
improved O
clinical O
deterioration O
and O
pneumonia O
duration O
in O
under O
five O
. O
The O
effect O
on O
preventing O
COVID-19 O
morbidity O
and O
related O
- O
death O
was O
lacking O
. O
Conclusions O
. O
Although O
the O
effects O
of O
vitamins O
and O
zinc O
on O
ARIs O
including O
COVID-19 O
were O
inconclusive O
, O
taking O
these O
for O
a O
short O
period O
during O
pandemic O
may O
be O
beneficial O
when O
there O
is O
risks O
of O
deficiency O
. O
Infection O
of O
a O
maternal O
urachal O
cyst O
during O
pregnancy O
is O
rare O
; O
Sonography O
is O
an O
important O
diagnostic O
tool O
that O
can O
help O
minimize O
maternal O
and O
fetal O
complications O
. O
We O
describe O
the O
case O
of O
a O
35 O
- O
year O
- O
old O
multiparous O
woman O
presenting O
in O
the O
third O
trimester O
with O
2 O
weeks O
of O
fever O
, O
abdominal O
pain O
, O
and O
urinary O
symptoms O
. O
Imaging O
showed O
a O
5 O
- O
cm O
complex O
anterior O
midline O
mass O
, O
found O
intraoperatively O
to O
be O
eroding O
into O
the O
uterus O
. O
Sonographic O
imaging O
aided O
in O
the O
diagnosis O
and O
management O
of O
the O
urachal O
cyst O
, O
and O
antepartum O
sonographic O
measurements O
of O
the O
lower O
uterine O
segment O
helped O
to O
counsel O
regarding O
a O
trial O
of O
labor O
. O
Following O
treatment O
, O
the O
patient O
stabilized O
and O
had O
an O
uncomplicated O
vaginal O
delivery O
. O
Context O
Because O
the O
skin O
and O
modified O
mucosal O
surfaces O
of O
the O
vulvar O
region O
contain O
dense O
apocrine O
glands O
and O
anogenital O
mammary O
- O
like O
glands O
, O
in O
addition O
to O
eccrine O
glands O
and O
folliculosebaceous O
units O
, O
benign O
as O
well O
as O
malignant O
lesions O
derived O
from O
these O
adnexal O
structures O
are O
, O
not O
surprisingly O
, O
found O
in O
the O
vulva O
. O
However O
, O
their O
incidence B-EPI
occurring O
in O
the O
vulva O
has O
not O
been O
reported O
, O
to O
our O
knowledge O
. O
Objective O
To O
determine O
the O
incidence B-EPI
of O
various O
vulvar O
adnexal O
lesions O
. O
Design O
We O
performed O
a O
retrospective O
review O
( O
1978 O
- O
2010 O
) O
of O
the O
cases O
at O
our O
institution O
. O
Results O
A O
total O
of O
189 O
vulvar O
adnexal O
lesions O
were O
identified O
. O
Most O
of O
these O
lesions O
were O
benign O
( O
133 O
of O
189 B-STAT
; O
70 O
% O
) O
, O
with O
hidradenoma O
papilliferum O
being O
the O
most O
common O
, O
followed O
by O
syringoma O
and O
various O
types O
of O
cysts O
. O
Rare O
cases O
of O
tubular O
adenoma O
, O
poroma O
, O
spiradenoma O
, O
hidradenoma O
, O
cylindroma O
, O
sebaceoma O
, O
and O
trichoepithelioma O
were O
identified O
. O
Malignant O
adnexal O
neoplasms O
comprised O
the O
remaining O
30 O
% O
( O
56 O
of O
189 O
) O
of O
the O
cases O
. O
Extramammary O
Paget O
disease O
was O
the O
most O
common O
( O
49 O
of O
56 O
) O
, O
and O
29 O
% O
( O
14 O
of O
49 O
) O
demonstrated O
an O
invasive O
component O
. O
Rare O
cases O
of O
basal O
cell O
carcinoma O
, O
sebaceous O
carcinoma O
, O
apocrine O
carcinoma O
, O
adenoid O
cystic O
carcinoma O
, O
and O
spiradenocarcinoma O
were O
identified O
. O
Conclusions O
In O
this O
retrospective O
review O
, O
we O
identified O
several O
benign O
entities O
that O
have O
not O
been O
previously O
reported O
on O
the O
vulva O
, O
namely O
pilomatricoma O
, O
poroma O
, O
spiradenoma O
, O
and O
sebaceoma O
. O
Hidradenoma O
papilliferum O
and O
extramammary O
Paget O
disease O
were O
the O
most O
common O
benign O
and O
malignant O
adnexal O
neoplasms O
, O
respectively O
. O
The O
spectrum O
of O
various O
vulvar O
adnexal O
lesions O
appears O
to O
reflect O
the O
frequency O
of O
the O
underlying O
glandular O
elements O
. O
Background O
Primary O
and O
secondary O
aortopathy O
are O
frequently O
encountered O
in O
patients O
with O
congenital O
heart O
disease O
. O
The O
aim O
of O
this O
study O
is O
to O
present O
our O
experience O
and O
the O
incidence B-EPI
of O
primary O
and O
secondary O
adult O
CHD O
- O
associated O
aortopathy O
. O
Methods O
The O
cohort O
is O
comprised O
of O
adult O
patients O
with O
congenital O
heart O
disease O
from O
the O
registry O
of O
the O
Eastern O
Slovakia O
Institute O
of O
Cardiovascular O
Diseases O
. O
Data O
from O
the O
last O
follow O
- O
up O
examinations O
are O
included O
in O
this O
study O
. O
In O
the O
primary O
and O
secondary O
aortopathy O
groups O
were O
35 O
and O
12 O
patients O
respectively O
. O
As O
a O
control O
group O
were O
selected O
64 O
patients O
with O
non O
aortopathy O
associated O
congenital O
heart O
disease O
( O
atrial O
and O
ventricular O
septal O
defect O
) O
. O
Results O
Patients O
with O
primary O
and O
secondary O
aortopathy O
had O
larger O
ascending O
aorta O
/ O
aortic O
root O
diameters O
than O
the O
control O
group O
( O
36.28 O
( O
26 O
- O
49 O
) O
mm O
vs O
30.25 O
( O
21 O
- O
41 O
) O
mm O
p O
= O
0.000113 O
, O
33.82 O
27 O
- O
49 O
) O
mm O
vs O
29.03 O
( O
19 O
- O
38)mm O
p O
= O
0.000366 O
and O
42.1 O
( O
30 O
- O
50 O
) O
mm O
vs O
30.25 O
( O
21 O
- O
41 O
) O
mm O
, O
p O
= O
0.000106 O
, O
35.67 O
( O
27 O
- O
48 O
) O
mm O
vs O
29.03 O
( O
19 O
- O
38 O
) O
mm O
, O
p O
= O
0.000119 O
respectively O
) O
. O
Moreover O
, O
patients O
with O
secondary O
aortopathy O
had O
statistically O
significant O
larger O
ascending O
aorta O
diameter O
compared O
to O
the O
patients O
with O
primary O
aortopathy O
( O
42.1 O
( O
30 O
- O
50 O
) O
mm O
vs O
36.28 O
( O
26 O
- O
49 O
) O
mm O
p O
= O
0.030 O
) O
. O
During O
the O
follow O
- O
up O
period O
, O
were O
performed O
only O
in O
2 O
patients O
( O
one O
from O
each O
group O
) O
operations O
on O
the O
aortic O
root O
and O
the O
ascending O
aorta O
due O
to O
aortic O
root O
or O
ascending O
aorta O
dilatation O
. O
Conclusion O
More O
patients O
with O
secondary O
aortopathy O
had O
dilated O
ascending O
aorta/ O
aortic O
root O
, O
as O
well O
as O
larger O
aortic O
diameters O
compare O
to O
the O
patients O
with O
primary O
aortopathy O
. O
Routine O
follow O
- O
up O
of O
these O
patients O
with O
attention O
to O
aortic O
diameter O
is O
necessary O
. O
Amoebiasis O
is O
a O
common O
infection O
widely O
prevalent B-EPI
in O
tropical O
countries O
with O
low O
income O
and O
poor O
sanitation O
. O
The O
clinical O
picture O
is O
usually O
nonspecific O
; O
however O
, O
invasion O
of O
the O
liver O
by O
Entamoeba O
histolytica O
could O
lead O
to O
an O
amoebic O
liver O
abscess O
( O
ALA O
) O
. O
It O
is O
relatively O
uncommon O
in O
women O
and O
children O
. O
Though O
rare O
, O
extension O
of O
ALA O
into O
the O
lungs O
, O
pleural O
cavity O
, O
and O
pericardium O
may O
prove O
fatal O
. O
Pericardial O
amoebiasis O
is O
a O
rare O
complication O
which O
, O
if O
not O
treated O
early O
, O
could O
result O
in O
cardiac O
tamponade O
and O
subsequent O
death O
. O
The O
standard O
management O
option O
is O
eradication O
with O
metronidazole O
along O
with O
the O
drainage O
of O
fluid O
from O
the O
liver O
abscess O
and O
pericardial O
effusion O
. O
Herein O
, O
we O
present O
a O
case O
of O
a O
seven O
- O
year O
- O
old O
male O
child O
with O
ALA O
, O
who O
developed O
signs O
and O
symptoms O
suggesting O
pericardial O
effusion O
within O
a O
few O
days O
of O
hospital O
admission O
. O
Early O
diagnosis O
of O
pericardial O
complication O
and O
successful O
management O
of O
abscess O
resolved O
the O
pericardial O
effusion O
. O
Background O
: O
Electrophysiological O
examination O
plays O
an O
important O
role O
in O
the O
diagnosis O
of O
X O
- O
linked O
Charcot O
- O
Marie O
- O
Tooth O
disease O
( O
CMTX1 O
) O
with O
transient O
central O
nervous O
system O
deficits O
. O
However O
, O
the O
electrophysiological O
features O
are O
seldom O
reported O
. O
Methods O
: O
We O
reviewed O
and O
analyzed O
published O
reports O
to O
determine O
the O
electrophysiological O
features O
of O
CMTX1 O
patients O
with O
transient O
central O
nervous O
system O
deficits O
. O
Results O
: O
A O
total O
of O
21 O
CMTX1 O
patients O
with O
transient O
central O
nervous O
system O
deficits O
were O
found O
in O
17 O
published O
case O
reports O
/ O
series O
. O
The O
age O
of O
onset O
ranged O
from O
0.5 O
to O
18 O
years O
( O
mean O
12.02 O
± O
0.78 O
years O
) O
. O
All O
patients O
were O
male O
. O
Recurrent O
episodes O
of O
central O
nervous O
system O
deficits O
were O
reported O
in O
all O
21 O
cases O
and O
resolved O
in O
periods O
ranging O
from O
several O
minutes O
to O
3 O
days O
. O
All O
20 O
patients O
who O
had O
MRIs O
at O
presentation O
had O
bilaterally O
symmetrical O
abnormal O
T2 O
/ O
Diffusion O
signals O
in O
the O
white O
matter O
without O
enhancement O
of O
gadolinium O
. O
All O
subsequent O
MRIs O
showed O
improvement O
or O
were O
within O
normal O
limits O
. O
The O
median O
motor O
nerve O
conduction O
velocity O
( O
MNCV O
) O
, O
motor O
latencies O
, O
and O
compound O
muscle O
action O
potential O
( O
CMAP O
) O
amplitude O
were O
the O
most O
commonly O
measurable O
electrophysiological O
parameters O
( O
85.7 O
% O
) O
. O
All O
cases O
that O
had O
MNCV O
at O
presentation O
had O
slower O
and O
significantly O
decreased O
MNCV O
compared O
with O
the O
normal O
value O
( O
34.1 O
± O
1.10 O
m O
/ O
s O
vs. O
46.8±2.05 O
m O
/ O
s O
, O
P O
< O
0.0001 O
; O
95 O
% O
CI O
, O
-17.4 O
to O
-7.92 O
) O
. O
The O
average O
variations O
of O
MNCV O
in O
median O
nerve O
, O
ulnar O
nerve O
, O
peroneal O
nerve O
, O
and O
tibial O
nerve O
were O
22.0 B-STAT
± O
5.96 O
% O
, O
27.6 O
± O
11.9 O
% O
, O
25.9 O
± O
4.36 O
% O
, O
and O
27.3 B-STAT
± O
4.30 O
% O
, O
respectively O
. O
All O
cases O
with O
measured O
sensory O
nerve O
conduction O
velocity O
( O
SNCV O
) O
at O
presentation O
had O
slower O
and O
significantly O
decreased O
SNCV O
compared O
with O
the O
normal O
value O
( O
35.3 O
± O
1.33 O
m O
/ O
s O
vs. O
47.7 O
± O
2.40 O
m O
/ O
s O
, O
P O
< O
0.001 O
; O
95 O
% O
CI O
-18.2 O
to O
-6.46 O
) O
. O
The O
average O
variations O
of O
SNCV O
in O
median O
nerve O
, O
ulnar O
nerve O
, O
and O
sural O
nerve O
were O
19.9 B-STAT
± O
8.24 O
% O
, O
25.2 O
± O
7.75 O
% O
, O
and O
23.2 O
± O
3.95 O
% O
, O
respectively O
. O
Conclusion O
: O
This O
case O
series O
serves O
as O
a O
reminder O
that O
electrophysiological O
examination O
should O
be O
included O
in O
the O
diagnosis O
of O
recurrent O
and O
episodic O
neurological O
deficit O
with O
white O
matter O
lesions O
. O
Median O
MNCV O
is O
a O
sensitive O
and O
valuable O
parameter O
to O
support O
the O
diagnosis O
of O
CMTX1 O
with O
transient O
central O
nervous O
system O
deficits O
. O
Most O
of O
the O
knowledge O
in O
pediatric O
antiphospholipid O
syndrome O
( O
APS O
) O
is O
derived O
from O
studies O
performed O
on O
the O
adult O
population O
. O
As O
in O
adults O
, O
antiphospholipid O
antibodies O
( O
aPL O
) O
can O
contribute O
to O
thrombosis O
, O
especially O
cerebrovascular O
thrombosis O
, O
in O
neonates O
and O
children O
. O
Since O
aPL O
have O
the O
potential O
to O
cross O
the O
placental O
barrier O
, O
and O
since O
the O
pediatric O
population O
is O
prone O
to O
infections O
, O
re O
- O
testing O
for O
their O
positivity O
is O
essential O
to O
specify O
their O
role O
in O
cerebrovascular O
thrombosis O
. O
In O
this O
review O
, O
we O
aimed O
at O
assessing O
the O
prevalence B-EPI
of O
aPL O
, O
criteria O
or O
non O
- O
criteria O
, O
in O
neonatal O
and O
childhood O
ischemic O
stroke O
and O
sinovenous O
thrombosis O
trying O
to O
find O
an O
association O
between O
aPL O
and O
cerebrovascular O
thrombosis O
in O
the O
neonatal O
and O
pediatric O
population O
. O
Also O
, O
we O
looked O
into O
the O
effect O
of O
aPL O
and O
anticoagulants O
/ O
antiplatelets O
on O
the O
long O
term O
neurological O
outcomes O
of O
affected O
neonates O
or O
children O
. O
The O
questions O
regarding O
the O
prevalence B-EPI
of O
aPL O
among O
pediatric O
patients O
with O
cerebrovascular O
thrombosis O
, O
the O
relationship O
between O
the O
titers O
of O
aPL O
and O
incidence B-EPI
and O
recurrence O
of O
cerebrovascular O
events O
, O
the O
predictability O
of O
the O
long O
term O
neurological O
outcomes O
, O
and O
the O
most O
optimal O
anticoagulation O
plan O
are O
still O
to O
be O
answered O
. O
However O
, O
it O
is O
crucial O
for O
clinicians O
to O
screen O
neonates O
and O
children O
with O
cerebrovascular O
thrombosis O
for O
aPL O
and O
confirm O
their O
presence O
if O
positive O
. O
Babies O
in O
Neonatal O
Intensive O
Care O
Units O
( O
NICU O
) O
have O
an O
additional O
risk O
for O
hearing O
loss O
due O
to O
various O
risk O
factors O
like O
, O
prematurity O
, O
low O
birth O
weight O
, O
mechanical O
ventilation O
, O
hyperbillirubinemia O
, O
ototoxic O
drugs O
, O
low O
APGAR O
score O
etc O
. O
as O
compared O
to O
the O
babies O
from O
well O
baby O
nursery O
( O
WBN O
) O
who O
, O
poses O
risk O
factors O
mostly O
family O
history O
, O
syndromic O
deafness O
. O
So O
the O
present O
study O
was O
aimed O
know O
the O
risk O
factors O
responsible O
for O
hearing O
loss O
in O
NICU O
and O
WBN O
babies O
and O
to O
assess O
the O
incidence B-EPI
of O
deafness O
. O
A O
total O
of O
800 O
babies O
from O
NICU O
( O
n O
= O
402 O
) O
and O
WBN O
( O
n O
= O
398 O
) O
underwent O
hearing O
screening O
from O
a O
tertiary O
care O
center O
. O
Hearing O
screening O
was O
done O
using O
two O
staged O
screening O
protocol O
as O
per O
JCIH O
guidelines O
with O
Distortion O
product O
Evoked O
Otoacoustic O
Emissions O
( O
DPOAE O
) O
and O
Automated O
Auditory O
Brainstem O
Responses O
( O
A O
- O
ABR O
) O
. O
According O
to O
DPOAE O
test O
, O
311 O
from O
NICU O
and O
383 O
from O
WBN O
passed O
the O
test O
and O
during O
second O
screening O
, O
80 O
out O
of O
91 O
from O
NICU O
and O
11 O
out O
of O
13 O
from O
WBN O
passed O
the O
DPOAE O
test O
. O
Further O
BERA O
was O
done O
at O
the O
3 O
rd O
month O
of O
corrected O
age O
where O
6 O
out O
of O
11 O
showed O
positive O
responses O
from O
NICU O
and O
3 O
babies O
from O
WBN O
had O
profound O
hearing O
loss O
. O
Data O
analysis O
revealed O
that O
family O
history O
of O
deafness O
, O
anemia O
and O
hypertension O
in O
ANC O
, O
TORCH O
in O
mother O
, O
low O
Apgar O
score O
and O
hyperbillirubinemia O
in O
newborns O
were O
a O
major O
risk O
factor O
for O
hearing O
impairment O
. O
We O
conclude O
that O
the O
diagnoses O
of O
auditory O
disorders O
at O
early O
stage O
due O
to O
various O
risk O
factors O
are O
important O
since O
appropriate O
therapeutic O
intervention O
and O
rehabilitation O
would O
help O
in O
better O
development O
of O
children O
. O
Background O
As O
a O
result O
of O
the O
current O
global O
pandemic O
, O
the O
dental O
profession O
has O
utilized O
teledentistry O
to O
reduce O
footfall O
in O
the O
hospitals O
and O
clinics O
where O
possible O
. O
Pediatric O
dental O
consultants O
form O
a O
vital O
part O
of O
a O
multidisciplinary O
team O
and O
regularly O
monitor O
the O
dental O
growth O
and O
development O
of O
patients O
with O
cleft O
lip O
and O
palate O
. O
Objective O
To O
assess O
the O
effectiveness O
of O
the O
service O
provided O
by O
pediatric O
dental O
consultants O
in O
the O
South O
Thames O
Cleft O
Service O
at O
Evelina O
Children O
's O
Hospital O
during O
the O
COVID-19 O
pandemic O
through O
virtual O
clinics O
. O
Design O
Data O
were O
collected O
retrospectively O
and O
include O
all O
cleft O
patients O
contacted O
via O
the O
virtual O
clinic O
during O
May O
to O
July O
2020 O
. O
Patients O
were O
prioritized O
by O
the O
Red O
, O
Amber O
, O
Green O
( O
RAG O
) O
scale O
to O
highlight O
the O
urgency O
of O
their O
next O
face O
- O
to O
- O
face O
appointment O
. O
Results O
A O
total O
of O
215 O
patients O
were O
contacted O
during O
this O
period O
with O
a O
97 O
% O
response O
rate O
. O
Patients O
given O
a O
RAG O
score O
of O
GREEN O
( O
86 O
% O
) O
meant O
no O
urgent O
requirement O
for O
a O
face O
- O
to O
- O
face O
consultation O
and O
AMBER O
( O
8 O
% O
) O
patients O
required O
treatment O
that O
was O
deemed O
nonurgent O
. O
However O
, O
3 O
% O
of O
patients O
received O
a O
RED O
rating O
as O
they O
required O
urgent O
input O
. O
Conclusion O
Through O
these O
virtual O
clinics O
, O
the O
pediatric O
team O
was O
able O
to O
reach O
208 O
patients O
and O
provided O
advice O
and O
reassurance O
. O
The O
need O
for O
face O
- O
to O
- O
face O
appointment O
was O
eliminated O
for O
11 O
% O
of O
patients O
who O
were O
discharged O
to O
their O
local O
dental O
practitioners O
, O
thereby O
reducing O
the O
risk O
of O
spreading O
COVID-19 O
. O
Of O
7,028 O
disorders O
with O
suspected O
Mendelian O
inheritance O
, O
1,139 O
are O
recessive O
and O
have O
an O
established O
molecular O
basis O
. O
Although O
individually O
uncommon O
, O
Mendelian O
diseases O
collectively O
account O
for O
~20 O
% O
of O
infant O
mortality O
and O
~18 O
% O
of O
pediatric O
hospitalizations O
. O
Molecular O
diagnostic O
testing O
is O
currently O
available O
for O
only O
~300 O
recessive O
disorders O
. O
Preconception O
screening O
, O
together O
with O
genetic O
counseling O
of O
carriers O
, O
has O
resulted O
in O
remarkable O
declines O
in O
the O
incidence B-EPI
of O
several O
severe O
recessive O
diseases O
including O
Tay O
- O
Sachs O
disease O
and O
cystic O
fibrosis O
. O
However O
, O
extension O
of O
preconception O
screening O
and O
molecular O
diagnostic O
testing O
to O
most O
recessive O
disease O
genes O
has O
hitherto O
been O
impractical O
. O
Recently O
, O
we O
reported O
a O
preconception O
carrier O
screen O
/ O
molecular O
diagnostic O
test O
for O
448 O
recessive O
childhood O
diseases O
. O
The O
current O
status O
of O
this O
test O
is O
reviewed O
here O
. O
Currently O
, O
this O
reports O
analytical O
validity O
of O
the O
comprehensive O
carrier O
test O
. O
As O
the O
clinical O
validity O
and O
clinical O
utility O
in O
the O
contexts O
described O
is O
ascertained O
, O
this O
article O
will O
be O
updated O
. O
Introduction O
: O
Intra O
- O
uterine O
adhesion O
( O
IUA O
) O
is O
one O
of O
the O
main O
causes O
of O
secondary O
infertility O
. O
The O
aim O
of O
this O
study O
was O
to O
evaluate O
the O
prevalence B-EPI
of O
IUA O
developing O
in O
women O
undergoing O
hysteroscopic O
resection O
for O
submucous O
myomas O
, O
polyps O
, O
and O
intrauterine O
synechiae O
and O
test O
the O
efficacy O
of O
second O
look O
hysteroscopy O
for O
diagnosing O
and O
treating O
post O
- O
surgical O
adhesions O
. O
Materials O
and O
Methods O
: O
We O
retrospectively O
collected O
data O
from O
reproductive O
age O
women O
who O
had O
a O
second O
look O
office O
hysteroscopy O
following O
hysteroscopic O
resection O
for O
myoma O
, O
polyp O
, O
or O
IUA O
at O
Foch O
hospital O
( O
Suresnes O
, O
France B-LOC
) O
between O
2009 O
and O
2017 O
. O
Results O
: O
Six O
hundred O
and O
twenty O
two O
reproductive O
- O
age O
women O
underwent O
hysteroscopic O
resection O
for O
myoma O
, O
polyp O
, O
and/or O
IUA O
. O
Among O
them O
, O
155 O
women O
had O
a O
second O
look O
hysteroscopy O
. O
In O
this O
group O
, O
29/155 B-STAT
( O
18.7 O
% O
) O
had O
IUA O
formation O
: O
17/83 B-STAT
( O
20.5 O
% O
) O
women O
who O
underwent O
hysteroscopic O
myomectomy O
, O
5/46 B-STAT
( O
10.9 O
% O
) O
women O
who O
underwent O
hysteroscopic O
polypectomy O
, O
and O
7/26 B-STAT
( O
26.9 O
% O
) O
women O
who O
underwent O
hysteroscopic O
lysis O
of O
adhesions O
. O
These O
IUA O
have O
been O
lysed O
by O
the O
office O
hysteroscopy O
procedure O
in O
16/29 B-STAT
( O
55.2 O
% O
) O
patients O
: O
11/17 B-STAT
( O
64.7 O
% O
) O
, O
2/5 B-STAT
( O
40 O
% O
) O
, O
and O
3/7 B-STAT
( O
42.9 O
% O
) O
in O
women O
who O
underwent O
hysteroscopic O
myomectomy O
, O
polypectomy O
and O
lysis O
of O
adhesion O
, O
respectively O
. O
Conclusion O
: O
IUA O
is O
a O
common O
complication O
of O
hysteroscopic O
surgery O
. O
Second O
look O
office O
hysteroscopy O
is O
an O
easy O
and O
effective O
procedure O
for O
diagnosing O
and O
removing O
newly O
formed O
IUA O
. O
It O
should O
be O
recommended O
for O
all O
women O
undergoing O
hysteroscopic O
resection O
for O
myomas O
, O
polyps O
, O
or O
IUA O
. O
Identifying O
which O
factors O
contribute O
to O
vitiligo O
severity O
and O
determining O
their O
individual O
weight O
are O
important O
in O
the O
management O
of O
vitiligo O
. O
The O
aim O
of O
this O
study O
is O
to O
investigate O
the O
predictive O
variables O
concerning O
vitiligo O
severity O
as O
perceived O
by O
the O
patients O
. O
Based O
on O
a O
questionnaire O
, O
several O
factors O
that O
may O
contribute O
to O
the O
Patient O
Global O
Assessment O
( O
PtGA O
) O
of O
severity O
were O
investigated O
within O
a O
Belgian O
vitiligo O
population O
( O
n O
= O
291 O
) O
. O
In O
addition O
, O
possible O
factors O
influencing O
vitiligo O
severity O
were O
scored O
and O
ranked O
. O
The O
strongest O
correlations O
with O
the O
PtGA O
of O
severity O
were O
found O
for O
impact O
, O
Dermatology O
Life O
Quality O
Index O
and O
disease O
extent O
. O
Based O
on O
multivariable O
regression O
analyses O
, O
64.7 O
% O
of O
PtGA O
of O
severity O
could O
be O
predicted O
by O
subjective O
and O
objective O
variables O
, O
while O
32 O
% O
could O
be O
explained O
by O
objective O
clinical O
features O
only O
. O
Patients O
considered O
lesion O
location O
, O
extent O
and O
disease O
activity O
as O
the O
most O
important O
contributing O
factors O
to O
severity O
. O
Vitiligo O
severity O
is O
determined O
by O
objective O
clinical O
features O
, O
but O
also O
, O
for O
a O
significant O
part O
, O
by O
the O
perceived O
impact O
of O
the O
disease O
. O
Background O
Moebius O
syndrome O
is O
a O
disorder O
characterized O
by O
facial O
and O
abducens O
nerve O
paralysis O
. O
Patients O
can O
present O
a O
wide O
range O
of O
upper O
extremity O
malformations O
. O
Literature O
focused O
on O
orthopedic O
manifestations O
of O
Moebius O
syndrome O
shows O
variability O
in O
the O
prevalence B-EPI
and O
clinical O
presentation O
of O
upper O
extremity O
anomalies O
. O
The O
aim O
of O
this O
work O
is O
to O
evaluate O
the O
prevalence B-EPI
of O
upper O
extremity O
malformations O
in O
patients O
with O
Moebius O
syndrome O
, O
clarify O
its O
various O
clinical O
presentations O
, O
and O
present O
treatment O
strategies O
for O
their O
management O
. O
Methods O
This O
is O
a O
retrospective O
, O
cross O
- O
sectional O
study O
including O
patients O
with O
Moebius O
syndrome O
and O
upper O
extremity O
malformations O
between O
2012 O
and O
2019 O
. O
Data O
include O
demographic O
characteristics O
, O
Moebius O
syndrome O
subtype O
, O
type O
of O
malformation O
, O
affected O
extremity O
, O
and O
surgical O
procedures O
underwent O
. O
Quantitative O
data O
were O
recorded O
as O
mean O
( O
standard O
deviation O
[ O
SD O
] O
) O
, O
and O
qualitative O
data O
were O
expressed O
in O
terms O
of O
totals O
and O
percentages O
. O
Statistical O
association O
between O
Moebius O
syndrome O
subtype O
and O
development O
of O
upper O
extremity O
anomalies O
was O
evaluated O
using O
binary O
logistic O
regression O
. O
Results O
Twenty O
- O
five O
out O
of O
153 O
patients O
( O
16.3 O
% O
) O
presented O
upper O
extremity O
malformations O
( O
48 O
% O
male O
) O
. O
Mean O
age O
of O
presentation O
was O
9.08 O
± O
9.43 O
years O
. O
Sixty B-STAT
- O
eight O
percent O
of O
the O
malformations O
were O
unilateral O
. O
The O
most O
common O
presentations O
included O
Poland B-LOC
syndrome O
and O
simple O
syndactyly O
with O
8 O
cases O
each O
( O
32 O
% O
) O
, O
followed O
by O
5 O
cases O
of O
brachysyndactyly O
( O
20 O
% O
) O
, O
3 O
cases O
of O
amniotic O
band O
syndrome O
( O
12 O
% O
) O
, O
and O
1 O
case O
of O
cleft O
hand O
( O
4 O
% O
) O
. O
No O
statistical O
association O
was O
found O
between O
Moebius O
syndrome O
subtype O
and O
odds O
ratio O
for O
development O
of O
upper O
extremity O
anomalies O
. O
Thirteen O
patients O
( O
52 O
% O
) O
underwent O
reconstructive O
procedures O
. O
Conclusion O
Poland B-LOC
syndrome O
and O
syndactyly O
are O
the O
most O
common O
anomalies O
in O
patients O
with O
Moebius O
syndrome O
. O
Patients O
may O
present O
with O
a O
wide O
range O
of O
hand O
malformations O
, O
each O
patient O
should O
be O
carefully O
evaluated O
in O
order O
to O
determine O
whether O
surgical O
treatment O
is O
needed O
and O
to O
optimize O
rehabilitation O
protocols O
. O
Neurodegeneration O
with O
brain O
iron O
accumulation O
( O
NBIA O
) O
is O
a O
group O
of O
rare O
neurogenetic O
degenerative O
diseases O
caused O
by O
genetic O
mutations O
and O
characterized O
by O
iron O
deposition O
in O
the O
central O
nervous O
system O
, O
especially O
in O
the O
basal O
ganglia O
, O
with O
an O
overall B-EPI
incidence I-EPI
rate O
of O
2/1 B-STAT
000 O
000 B-STAT
- I-STAT
3/1 I-STAT
000 I-STAT
000 I-STAT
. O
Major O
clinical O
manifestations O
are O
extrapyramidal O
symptoms O
. O
This O
disease O
is O
presently O
classified O
into O
14 O
different O
subtypes O
based O
on O
different O
pathogenic O
genes O
, O
and O
its O
pathogenesis O
and O
treatment O
remain O
unclear O
. O
This O
article O
summarizes O
the O
research O
advances O
in O
the O
pathogenesis O
and O
treatment O
of O
NBIA O
, O
so O
as O
to O
help O
pediatricians O
understand O
this O
disease O
and O
provide O
a O
reference O
for O
subsequent O
research O
on O
treatment O
. O
Autoimmune O
thyroid O
disease O
( O
ATD O
) O
is O
the O
most O
frequent O
cause O
of O
acquired O
thyroid O
dysfunction O
, O
most O
commonly O
presenting O
either O
as O
Hashimoto O
's O
thyroiditis O
or O
Graves O
' O
Disease O
. O
Hashimoto O
's O
thyroiditis O
is O
characterized O
by O
the O
presence O
of O
thyroid O
- O
specific O
autoantibodies O
, O
more O
commonly O
anti O
- O
thyroperoxidase O
antibodies O
in O
the O
serum O
and O
the O
typical O
inhomogeneous O
echostructure O
of O
the O
thyroid O
on O
a O
thyroid O
ultrasound O
examination O
. O
Hashimoto O
's O
thyroiditis O
can O
for O
a O
long O
time O
be O
accompanied O
by O
normal O
thyroid O
function O
and O
hypothyroidism O
can O
only O
progressively O
be O
established O
. O
Graves O
' O
disease O
is O
much O
less O
frequent O
in O
childhood O
and O
adolescence O
and O
presents O
with O
overt O
hyperthyroidism O
. O
After O
the O
onset O
of O
puberty O
, O
ATD O
affects O
females O
with O
a O
higher O
incidence B-EPI
than O
males O
, O
while O
during O
the O
prepubertal O
period O
there O
is O
not O
such O
a O
clear O
preponderance O
of O
affected O
females O
. O
ATD O
can O
occur O
either O
isolated O
or O
in O
the O
context O
of O
other O
autoimmune O
disorders O
, O
such O
as O
type O
1 O
Diabetes O
mellitus O
( O
T1D O
) O
, O
celiac O
disease O
, O
alopecia O
areata O
, O
vitiligo O
, O
etc O
. O
Especially O
at O
the O
pediatric O
age O
, O
a O
higher O
incidence B-EPI
of O
ATD O
is O
also O
observed O
in O
the O
context O
of O
specific O
genetic O
syndromes O
, O
such O
as O
trisomy O
21 O
( O
Down O
syndrome O
) O
, O
Klinefelter O
syndrome O
, O
Turner O
syndrome O
, O
or O
22q11.2 O
deletion O
syndrome O
. O
Nevertheless O
, O
although O
thyroid O
dysfunction O
may O
also O
be O
observed O
in O
other O
genetic O
syndromes O
, O
such O
as O
Prader O
- O
Willi O
or O
Williams O
syndrome O
, O
the O
thyroid O
dysfunction O
in O
these O
syndromes O
is O
not O
the O
result O
of O
thyroid O
autoimmunity O
. O
Interestingly O
, O
there O
is O
emerging O
evidence O
supporting O
a O
possible O
link O
between O
autoimmunity O
and O
RASopathies O
. O
In O
this O
review O
article O
the O
incidence B-EPI
, O
as O
well O
as O
the O
clinical O
manifestation O
and O
accompanied O
pathologies O
of O
ATD O
in O
specific O
genetic O
syndromes O
will O
be O
presented O
and O
regular O
follow O
- O
up O
for O
the O
early O
identification O
of O
the O
disorder O
will O
be O
proposed O
. O
Objectives O
A O
low O
serum O
alkaline O
phosphatase O
( O
ALP O
) O
level O
is O
an O
uncommon O
finding O
in O
patients O
with O
chronic O
liver O
disease O
( O
CLD O
) O
. O
The O
prevalence B-EPI
of O
this O
finding O
and O
whether O
low O
ALP O
expression O
influences O
CLD O
remain O
to O
be O
determined O
. O
The O
objectives O
of O
this O
study O
were O
: O
( O
1 O
) O
to O
document O
the O
prevalence B-EPI
of O
low O
serum O
ALP O
levels O
in O
adult O
CLD O
patients O
and O
( O
2 O
) O
compare O
features O
of O
CLD O
in O
patients O
with O
low O
versus O
normal O
or O
elevated O
serum O
ALP O
levels O
. O
Methods O
An O
adult O
, O
outpatient O
liver O
disease O
database O
was O
searched O
for O
patients O
with O
low O
serum O
ALP O
levels O
( O
< O
40 O
IU O
/ O
L O
) O
. O
Hepatic O
inflammation O
, O
function O
, O
fibrosis O
and O
disease O
severity O
were O
determined O
by O
serum O
aminotransferases O
, O
albumin O
, O
bilirubin O
and O
INR O
levels O
, O
Fib-4 O
calculations O
and O
MELD O
scores O
respectively O
. O
Results O
Of O
19,037 O
patients O
entered O
into O
the O
database O
, O
47 B-STAT
( I-STAT
0.25 I-STAT
% I-STAT
) O
had O
consistently O
low O
serum O
ALP O
levels O
, O
51 B-STAT
( I-STAT
0.27 I-STAT
% I-STAT
) O
low O
levels O
on O
the O
majority O
and O
469 B-STAT
( O
2.44 O
% O
) O
on O
the O
minority O
of O
determinations O
. O
Patients O
with O
consistently O
low O
levels O
were O
matched O
( O
1:2 B-STAT
) O
by O
age O
, O
gender O
and O
nature O
of O
the O
underlying O
liver O
disease O
to O
patients O
with O
normal O
or O
elevated O
serum O
ALP O
levels O
. O
Matched O
patients O
with O
consistently O
low O
ALP O
levels O
had O
significantly O
lower O
serum O
aminotransferase O
and O
bilirubin O
levels O
at O
their O
initial O
visit O
and O
throughout O
the O
follow O
- O
up O
period O
( O
p O
< O
0.05 O
respectively O
) O
while O
Fib-4 O
levels O
and O
MELD O
scores O
were O
similar O
at O
the O
initial O
and O
last O
follow O
- O
up O
visit O
. O
Conclusions O
These O
results O
establish O
the O
prevalence B-EPI
of O
low O
serum O
ALP O
levels O
in O
adult O
CLD O
patients O
and O
describe O
a O
hitherto O
unreported O
association O
between O
low O
serum O
ALP O
levels O
and O
less O
biochemical O
evidence O
of O
active O
disease O
. O
The O
aim O
of O
this O
study O
was O
to O
analyze O
the O
genetic O
variants O
of O
51 O
Chinese O
patients O
with O
distal O
renal O
tubular O
acidosis O
( O
dRTA O
) O
and O
explore O
the O
correlation O
between O
their O
genotype O
and O
phenotype O
. O
Eight O
variants O
of O
SLC4A1 O
, O
19 O
variants O
of O
ATP6V0A4 O
, O
and O
16 O
variants O
of O
ATP6V1B1 O
have O
been O
identified O
, O
and O
of O
which O
14 O
were O
novel O
ones O
. O
Eleven O
patients O
with O
autosomal O
dominant O
dRTA O
, O
and O
four O
patients O
with O
autosomal O
recessive O
dRTA O
were O
caused O
by O
genetic O
defects O
in O
SLC4A1 O
; O
18 O
and O
nine O
patients O
with O
recessive O
dRTA O
were O
resulted O
by O
defects O
in O
ATP6V0A4 O
and O
ATP6V1B1 O
respectively O
; O
no O
causal O
gene O
was O
identified O
in O
seven O
patients O
. O
Mutation O
frequency O
of O
SLC4A1 O
in O
Chinese O
populations O
was O
more O
common O
than O
Europeans O
. O
The O
incidence B-EPI
of O
deafness O
in O
ATP6V0A4 O
and O
ATP6V1B1 O
groups O
was O
16.7 O
% O
and O
54.5 O
% O
, O
respectively O
. O
The O
frequency O
of O
CKD O
in O
adults O
, O
children O
and O
infants O
was O
100 O
% O
, O
51 O
% O
, O
and O
3 O
% O
, O
separately O
. O
Our O
study O
will O
further O
expand O
the O
mutation O
spectrum O
of O
primary O
dRTA O
and O
provide O
valuable O
references O
to O
genetic O
counseling O
of O
Chinese O
populations O
. O
Introduction O
Cerebellar O
degeneration O
has O
been O
associated O
in O
patients O
with O
epilepsy O
, O
though O
the O
exact O
pathogenic O
mechanisms O
are O
not O
understood O
. O
The O
aim O
of O
this O
systematic O
review O
was O
to O
identify O
the O
prevalence B-EPI
of O
cerebellar O
degeneration O
in O
patients O
with O
epilepsy O
and O
identify O
any O
pathogenic O
mechanisms O
. O
Methodology O
A O
systematic O
computer O
- O
based O
literature O
search O
was O
conducted O
using O
the O
PubMed O
database O
. O
Data O
extracted O
included O
prevalence B-EPI
, O
clinical O
, O
neuroradiological O
, O
and O
neuropathological O
characteristics O
of O
patients O
with O
epilepsy O
and O
cerebellar O
degeneration O
. O
Results O
We O
identified O
three O
consistent O
predictors O
of O
cerebellar O
degeneration O
in O
the O
context O
of O
epilepsy O
in O
our O
review O
: O
temporal O
lobe O
epilepsy O
, O
poor O
seizure O
control O
, O
and O
phenytoin O
as O
the O
treatment O
modality O
. O
Whole O
brain O
and O
hippocampal O
atrophy O
were O
also O
identified O
in O
patients O
with O
epilepsy O
. O
Conclusions O
Cerebellar O
degeneration O
is O
prevalent B-EPI
in O
patients O
with O
epilepsy O
. O
Further O
prospective O
studies O
are O
required O
to O
confirm O
if O
the O
predictors O
identified O
in O
this O
review O
are O
indeed O
linked O
to O
cerebellar O
degeneration O
and O
to O
establish O
the O
pathogenic O
mechanisms O
that O
result O
in O
cerebellar O
insult O
. O
Purpose O
Our O
goal O
was O
to O
assess O
the O
prevalence B-EPI
of O
ipsilateral O
distal O
femoral O
osteochondritis O
dissecans O
( O
OCD)-like O
lesions O
in O
children O
with O
Blount O
disease O
, O
including O
factors O
associated O
with O
this O
finding O
. O
Materials O
and O
methods O
Characteristics O
of O
patients O
with O
an O
OCD O
- O
like O
lesion O
on O
an O
imaging O
study O
[ O
( O
X O
- O
ray O
and/or O
magnetic O
resonance O
imaging O
( O
MRI O
) O
] O
were O
compared O
with O
those O
without O
such O
a O
finding O
. O
Results O
Over O
a O
12 O
- O
year O
period O
, O
6/63 B-STAT
( O
10 O
% O
) O
skeletally O
immature O
patients O
( O
9/87 B-STAT
limbs O
) O
with O
Blount O
disease O
had O
an O
OCD O
- O
like O
lesion O
visible O
on O
plain O
radiographs O
. O
Based O
on O
available O
MRI O
, O
7/37 B-STAT
( O
19 O
% O
) O
patients O
or O
10/53 B-STAT
( O
19 O
% O
) O
limbs O
had O
an O
OCD O
- O
like O
distal O
femoral O
lesion O
. O
All O
lesions O
were O
noted O
in O
the O
posterior O
third O
of O
the O
weight O
- O
bearing O
portion O
of O
the O
medial O
femoral O
condyle O
with O
intact O
overlying O
articular O
cartilage O
. O
All O
patients O
with O
OCD O
- O
like O
lesions O
were O
followed O
for O
an O
average O
of O
1.9 O
years O
( O
range O
: O
1 O
- O
2.6 O
years O
) O
, O
and O
complete O
radiographic O
resolution O
of O
lesion O
was O
noted O
in O
7/9 B-STAT
limbs O
( O
78 O
% O
) O
. O
There O
was O
no O
association O
of O
the O
presence O
of O
OCD O
- O
like O
lesion O
with O
early- O
vs O
late O
- O
onset O
disease O
, O
gender O
, O
age O
at O
imaging O
, O
laterality O
, O
magnitude O
of O
deformity O
[ O
mean O
mechanical O
axis O
deviation O
( O
MAD O
) O
63.3 O
vs O
71.9 O
mm O
] O
, O
mean O
mechanical O
lateral O
distal O
femoral O
angle O
( O
mLDFA O
; O
91.3 O
vs O
89.7 O
° O
) O
, O
and O
mean O
medial O
proximal O
tibial O
angle O
( O
MPTA O
; O
71.7 O
vs O
71.8 O
° O
) O
. O
Children O
with O
an O
OCD O
- O
like O
lesion O
tended O
to O
have O
a O
lower O
mean O
body O
mass O
index O
( O
BMI O
; O
21 O
vs O
36 O
, O
p O
= O
0.003 O
) O
. O
Conclusion O
The O
overall B-EPI
prevalence I-EPI
of O
OCD O
- O
like O
lesions O
in O
the O
medial O
femoral O
condyle O
in O
children O
with O
Blount O
disease O
lesions O
is O
10 O
% O
using O
plain O
radiographs O
and O
at O
least B-STAT
19 O
% O
on O
MRI O
. O
Based O
on O
the O
numbers O
available O
, O
we O
were O
unable O
to O
demonstrate O
any O
associations O
between O
the O
presence O
of O
such O
lesions O
and O
the O
patient O
's O
age O
, O
gender O
, O
or O
magnitude O
of O
varus O
deformity O
. O
Further O
research O
is O
needed O
to O
fully O
ascertain O
the O
aetiology O
and O
natural O
history O
of O
these O
benign O
appearing O
osteochondral O
imaging O
findings O
in O
children O
with O
Blount O
disease O
. O
Our O
current O
data O
support O
that O
these O
lesions O
do O
resolve O
with O
time O
and O
that O
no O
surgical O
intervention O
targeted O
at O
the O
femoral O
OCD O
- O
like O
lesion O
is O
warranted O
. O
Level O
of O
evidence O
Diagnostic O
study O
Level O
III O
. O
How O
to O
cite O
this O
article O
Edobor O
- O
Osula O
F O
, O
Wenokor O
C O
, O
Bloom O
T O
, O
et O
al O
. O
Ipsilateral O
Osteochondritis O
Dissecans O
- O
like O
Distal O
Femoral O
Lesions O
in O
Children O
with O
Blount O
Disease O
: O
Prevalence B-EPI
and O
Associated O
Findings O
. O
Strategies O
Trauma O
Limb O
Reconstr O
2019;14(3):121 O
- O
125 O
. O
Charcot O
- O
Marie O
- O
Tooth O
( O
CMT O
) O
disease O
is O
the O
most O
common O
inherited O
neuropathy O
and O
one O
of O
the O
most O
common O
inherited O
diseases O
in O
humans O
. O
The O
diagnosis O
of O
CMT O
is O
traditionally O
made O
by O
the O
neurologic O
specialist O
, O
yet O
the O
optimal O
management O
of O
CMT O
patients O
includes O
genetic O
counselors O
, O
physical O
and O
occupational O
therapists O
, O
physiatrists O
, O
orthotists O
, O
mental O
health O
providers O
, O
and O
community O
resources O
. O
Rapidly O
developing O
genetic O
discoveries O
and O
novel O
gene O
discovery O
techniques O
continue O
to O
add O
a O
growing O
number O
of O
genetic O
subtypes O
of O
CMT O
. O
The O
first O
large O
clinical O
natural O
history O
and O
therapeutic O
trials O
have O
added O
to O
our O
knowledge O
of O
each O
CMT O
subtype O
and O
revealed O
how O
CMT O
impacts O
patient O
quality O
of O
life O
. O
In O
this O
review O
, O
we O
discuss O
several O
important O
trends O
in O
CMT O
research O
factors O
that O
will O
require O
a O
collaborative O
multidisciplinary O
approach O
. O
These O
include O
the O
development O
of O
large O
multicenter O
patient O
registries O
, O
standardized O
clinical O
instruments O
to O
assess O
disease O
progression O
and O
disability O
, O
and O
increasing O
recognition O
and O
use O
of O
patient O
- O
reported O
outcome O
measures O
. O
These O
developments O
will O
continue O
to O
guide O
strategies O
in O
long O
- O
term O
multidisciplinary O
efforts O
to O
maintain O
quality O
of O
life O
and O
preserve O
functionality O
in O
CMT O
patients O
. O
The O
human O
T O
cell O
lymphotropic O
virus O
type O
1 O
( O
HTLV-1 O
) O
is O
the O
first O
human O
retrovirus O
discovered O
. O
Since O
then O
, O
it O
has O
spread O
worldwide B-LOC
and O
is O
mainly O
associated O
with O
adult O
T O
cell O
leukemia O
/ O
lymphoma O
( O
ATLL O
) O
and O
HTLV1 O
- O
associated O
myelopathy O
( O
HAM O
) O
. O
Its O
relationship O
, O
however O
, O
with O
other O
types O
of O
cancer O
is O
controversial O
. O
We O
describe O
the O
case O
of O
a O
patient O
presenting O
with O
small O
cells O
lung O
epidermoid O
carcinoma O
who O
had O
recently O
developed O
HAM O
, O
and O
a O
review O
of O
the O
literature O
related O
to O
these O
conditions O
. O
This O
is O
the O
first O
case O
of O
this O
type O
of O
lung O
cancer O
, O
the O
same O
of O
the O
first O
description O
in O
the O
literature O
, O
associated O
with O
HAM O
outside O
Japan B-LOC
. O
BACKGROUND O
Vascular O
type O
of O
Ehlers O
- O
Danlos O
syndrome O
( O
vEDS O
) O
is O
a O
rare O
connective O
tissue O
disorder O
associated O
with O
a O
high O
prevalence B-EPI
rate O
of O
aortic O
dissection O
( O
AD O
) O
. O
The O
coexistence O
of O
a O
pregnancy O
raises O
these O
rates O
and O
the O
diagnostic O
complexity O
of O
the O
situation O
. O
In O
this O
article O
, O
we O
present O
a O
different O
initial O
diagnostic O
approach O
to O
an O
acute O
aortic O
syndrome O
. O
CASE O
REPORT O
A O
young O
pregnant O
woman O
( O
29th O
week O
gestation O
) O
with O
vEDS O
was O
admitted O
to O
our O
clinic O
due O
to O
sudden O
tearing O
back O
pain O
radiating O
to O
the O
left O
arm O
. O
Four O
years O
ago O
, O
the O
same O
patient O
underwent O
a O
surgical O
aortic O
valve O
reconstruction O
and O
replace O
of O
the O
ascending O
and O
proximal O
arch O
of O
the O
aorta O
because O
of O
an O
acute O
Standford O
A O
AD O
. O
The O
clinical O
, O
laboratory O
as O
well O
as O
transthoracic O
echocardiographic O
findings O
did O
not O
reveal O
any O
objective O
signs O
of O
an O
acute O
aortic O
syndrome O
. O
Due O
to O
the O
relative O
contraindications O
against O
computed O
tomography O
imaging O
due O
to O
pregnancy O
, O
we O
conducted O
a O
transesophageal O
echocardiography O
which O
revealed O
acute O
progress O
of O
pre O
- O
existing O
AD O
. O
A O
follow O
- O
up O
computed O
tomography O
could O
verify O
our O
findings O
, O
showing O
a O
Standford O
B O
dissection O
, O
which O
was O
treated O
conservatively O
. O
After O
2 O
weeks O
, O
due O
to O
a O
distal O
progression O
of O
dissection O
, O
our O
patient O
underwent O
a O
cesarean O
section O
. O
In O
absence O
of O
new O
clinical O
findings O
, O
the O
young O
patient O
was O
discharged O
the O
following O
week O
. O
CONCLUSIONS O
Patients O
with O
vEDS O
are O
at O
high O
risk O
of O
an O
AD O
and O
other O
life O
- O
threatening O
complications O
, O
especially O
during O
pregnancy O
. O
According O
to O
the O
guidelines O
of O
European O
Society O
of O
Cardiology O
( O
ESC O
) O
, O
vEDS O
- O
patients O
should O
be O
thoroughly O
screened O
. O
In O
the O
case O
of O
pregnancy O
, O
physicians O
should O
consider O
frequent O
follow O
- O
up O
examinations O
and O
be O
prepared O
for O
diagnosis O
and O
treatment O
of O
the O
potential O
complications O
. O
Objective O
The O
Global O
FKRP O
Registry O
is O
a O
database O
for O
individuals O
with O
conditions O
caused O
by O
mutations O
in O
the O
Fukutin O
- O
Related O
Protein O
( O
FKRP O
) O
gene O
: O
limb O
girdle O
muscular O
dystrophy O
R9 O
( O
LGMDR9 O
, O
formerly O
LGMD2I O
) O
and O
congenital O
muscular O
dystrophies O
MDC1C O
, O
Muscle O
- O
Eye O
- O
Brain O
Disease O
and O
Walker O
- O
Warburg O
Syndrome O
. O
The O
registry O
seeks O
to O
further O
understand O
the O
natural O
history O
and O
prevalence B-EPI
of O
FKRP O
- O
related O
conditions O
; O
aid O
the O
rapid O
identification O
of O
eligible O
patients O
for O
clinical O
studies O
; O
and O
provide O
a O
source O
of O
information O
to O
clinical O
and O
academic O
communities O
. O
Methods O
Registration O
is O
patient O
- O
initiated O
through O
a O
secure O
online O
portal O
. O
Data O
, O
reported O
by O
both O
patients O
and O
their O
clinicians O
, O
include O
: O
age O
of O
onset O
, O
presenting O
symptoms O
, O
family O
history O
, O
motor O
function O
and O
muscle O
strength O
, O
respiratory O
and O
cardiac O
function O
, O
medication O
, O
quality O
of O
life O
and O
pain O
. O
Results O
Of O
663 O
registered O
participants O
, O
305 O
were O
genetically O
confirmed O
LGMDR9 O
patients O
from O
23 O
countries O
. O
A O
majority O
of O
LGMDR9 O
patients O
carried O
the O
common O
mutation O
c.826C O
> O
A O
on O
one O
or O
both O
alleles O
; O
67.9 O
% O
were O
homozygous O
and O
28.5 O
% O
were O
compound O
heterozygous O
for O
this O
mutation O
. O
The O
mean O
ages O
of O
symptom O
onset O
and O
disease O
diagnosis O
were O
higher O
in O
individuals O
homozygous O
for O
c.826C O
> O
A O
compared O
with O
individuals O
heterozygous O
for O
c.826C O
> O
A. O
This O
divergence O
was O
replicated O
in O
ages O
of O
loss O
of O
running O
ability O
, O
wheelchair O
- O
dependence O
and O
ventilation O
assistance O
; O
consistent O
with O
the O
milder O
phenotype O
associated O
with O
individuals O
homozygous O
for O
c.826C O
> O
A. O
In O
LGMDR9 O
patients O
, O
75.1 O
% O
were O
currently O
ambulant O
and O
24.6 O
% O
, O
nonambulant O
( O
unreported O
in O
0.3 B-STAT
% I-STAT
) O
. O
Cardiac O
impairment O
was O
reported O
in O
23.2 O
% O
( O
30/129 O
) O
. O
Interpretation O
The O
Global O
FKRP O
Registry O
enables O
the O
collection O
of O
patient O
natural O
history O
data O
, O
which O
informs O
academics O
, O
healthcare O
professionals O
and O
industry O
. O
It O
represents O
a O
trial O
- O
ready O
cohort O
of O
individuals O
and O
is O
centrally O
placed O
to O
facilitate O
recruitment O
to O
clinical O
studies O
. O
Background O
: O
It O
has O
been O
estimated O
that O
27.8 O
million O
neonates O
will O
die O
worldwide B-LOC
between O
2018 O
and O
2030 O
if O
no O
improvements O
in O
neonatal O
and O
maternal O
care O
take O
place O
. O
The O
aim O
of O
this O
study O
was O
to O
determine O
the O
rate O
, O
risk O
factors O
, O
and O
causes O
of O
neonatal O
mortality O
in O
Jordan B-LOC
. O
Methods O
: O
In O
August O
2019 O
, O
an O
electronic O
stillbirths O
and O
neonatal O
deaths O
surveillance O
system O
( O
JSANDS O
) O
was O
established O
in O
in O
three O
large O
cities O
through O
five O
hospitals O
. O
Data O
on O
all O
births O
, O
neonatal O
mortality O
and O
their O
causes O
, O
and O
other O
characteristics O
in O
the O
period O
between O
August O
2019 O
and O
January O
2020 O
were O
exported O
from O
the O
JSANDS O
and O
analyzed O
. O
Results O
: O
A O
total O
of O
10,328 O
births O
[ O
10,226 O
live O
births O
( O
LB O
) O
and O
102 O
stillbirths O
] O
were O
registered O
in O
the O
study O
period O
, O
with O
a O
rate O
of O
14.1 B-STAT
deaths I-STAT
per I-STAT
1,000 I-STAT
LBs I-STAT
; O
76 O
% O
were O
early O
neonatal O
deaths O
and O
24 O
% O
were O
late O
deaths O
. O
The O
odds O
of O
deaths O
in O
the O
Ministry O
of O
Health O
hospitals O
were O
almost O
21 O
times O
( O
OR O
= O
20.8 O
, O
95 O
% O
CI O
: O
2.8 O
, O
153.1 O
) O
higher O
than O
that O
in O
private O
hospitals O
. O
Low O
birthweight O
and O
pre O
- O
term O
babies O
were O
significantly O
more O
likely O
to O
die O
during O
the O
neonatal O
period O
compared O
to O
full O
- O
term O
babies O
. O
The O
odds O
of O
neonatal O
mortality O
were O
significantly O
higher O
among O
babies O
born O
to O
housewives O
compared O
to O
those O
who O
were O
born O
to O
employed O
women O
( O
OR O
= O
2.7 O
; O
95 O
% O
CI O
: O
1.2 O
, O
6.0 O
) O
. O
Main O
causes O
of O
neonatal O
deaths O
that O
occurred O
pre O
- O
discharge O
were O
respiratory O
and O
cardiovascular O
disorders O
( O
43 O
% O
) O
and O
low O
birthweight O
and O
pre O
- O
term O
( O
33 O
% O
) O
. O
The O
main O
maternal O
conditions O
that O
attributed O
to O
these O
deaths O
were O
complications O
of O
the O
placenta O
and O
cord O
, O
complications O
of O
pregnancy O
, O
and O
medical O
and O
surgical O
conditions O
. O
The O
main O
cause O
of O
neonatal O
deaths O
that O
occurred O
post O
- O
discharge O
were O
low O
birthweight O
and O
pre O
- O
term O
( O
42 O
% O
) O
. O
Conclusions O
: O
The O
rate O
of O
neonatal O
mortality O
have O
not O
decreased O
since O
2012 O
and O
the O
majority O
of O
neonatal O
deaths O
occurred O
could O
have O
been O
prevented O
. O
Regular O
antenatal O
visits O
, O
in O
which O
any O
possible O
diseases O
or O
complications O
of O
pregnant O
women O
or O
fetal O
anomalies O
, O
need O
to O
be O
fully O
documented O
and O
monitored O
with O
appropriate O
and O
timely O
medical O
intervention O
to O
minimize O
such O
deaths O
. O
Ophiogomphus O
howei O
Bromley B-LOC
is O
a O
rare O
North O
American O
dragonfly O
, O
given O
a O
global O
conservation O
rank O
of O
Vulnerable O
by O
NatureServe O
. O
This O
species O
inhabits O
localized O
stretches O
of O
a O
limited O
number O
of O
typically O
undisturbed O
, O
high O
- O
quality O
, O
forested O
rivers O
in O
two O
disjunct O
regions O
in O
North B-LOC
America I-LOC
. O
We O
describe O
a O
new O
population O
in O
between O
the O
known O
ranges O
from O
an O
impaired O
river O
in O
a O
largely O
urban O
watershed O
in O
southern O
Michigan B-LOC
, O
United B-LOC
States I-LOC
. O
We O
also O
report O
a O
previously O
overlooked O
specimen O
from O
a O
new O
location O
in O
Pennsylvania B-LOC
, O
United B-LOC
States I-LOC
, O
and O
provide O
current O
occurrence B-EPI
and O
conservation O
status O
of O
the O
species O
in O
North B-LOC
America I-LOC
. O
Background O
Charcot O
- O
Marie O
- O
Tooth O
disease O
Type O
2A O
( O
CMT2A O
) O
presents O
with O
optic O
atrophy O
in O
a O
subset O
of O
patients O
, O
but O
the O
prevalence B-EPI
and O
severity O
of O
optic O
nerve O
involvement O
in O
relation O
to O
other O
CMT O
subtypes O
has O
not O
been O
explored O
. O
Methods O
Patients O
with O
genetically O
confirmed O
CMT2A O
( O
n O
= O
5 O
) O
, O
CMT1A O
( O
n O
= O
9 O
) O
and O
CMTX1 O
( O
n O
= O
10 O
) O
underwent O
high- B-LOC
and O
low O
- O
contrast O
acuity O
testing O
using O
Sloan O
letter O
charts O
, O
and O
circumpapillary O
retinal O
nerve O
fiber O
layer O
( O
RNFL O
) O
and O
macular O
total O
retinal O
, O
RNFL O
, O
and O
ganglion O
cell O
layer O
/ O
inner O
plexiform O
layer O
thickness O
was O
measured O
using O
spectral O
domain O
optical O
coherence O
tomography O
( O
OCT O
) O
. O
We O
used O
age- O
and O
gender O
- O
adjusted O
linear O
regression O
to O
compare O
contrast O
acuity O
and O
retinal O
thickness O
between O
CMT O
groups O
. O
Results O
One B-STAT
of I-STAT
5 I-STAT
patients O
with O
CMT2A O
had O
optic O
nerve O
atrophy O
( O
binocular O
high O
- O
contrast O
acuity O
equivalent O
20/160 B-STAT
, O
mean O
circumpapillary O
RNFL O
47.5 O
μm O
) O
. O
The O
other O
patients O
with O
CMT2A O
had O
normal O
high- O
and O
low O
- O
contrast O
acuity O
and O
retinal O
thickness O
, O
and O
there O
were O
no O
significant O
differences O
between O
patients O
with O
CMT2A B-LOC
, O
CMT1A O
, O
and O
CMTX1 O
. O
Conclusions O
Optic O
atrophy O
occurs B-EPI
in O
some O
patients O
with O
CMT2A O
, O
but O
in O
others O
, O
there O
is O
no O
discernible O
optic O
nerve O
involvement O
. O
This O
suggests O
that O
optic O
neuropathy O
is O
specific O
to O
certain O
MFN2 O
mutations O
in O
CMT2A O
and O
that O
low O
- O
contrast O
acuity O
or O
OCT O
is O
of O
limited O
value O
as O
a O
disease O
- O
wide O
biomarker O
. O
Coxiella O
burnetii O
is O
an O
intracellular O
bacterium O
and O
the O
cause O
of O
the O
zoonotic O
infection O
, O
Q O
fever O
. O
National O
surveillance O
data O
on O
C. O
burnetii O
seroprevalence O
is O
currently O
not O
available O
for O
any O
South O
American O
country O
, O
making O
efforts O
of O
public O
health O
to O
implement O
strategies O
to O
mitigate O
infections O
in O
different O
at O
- O
risk O
groups O
within O
the O
population O
extremely O
challenging O
. O
In O
the O
current O
study O
, O
we O
used O
two O
commercial O
anti- O
C. O
burnetii O
immunoassays O
to O
screen O
sera O
collected O
from O
a O
sample O
of O
the O
Chilean O
population O
as O
part O
of O
a O
2016 O
- O
2017 O
national O
health O
survey O
( O
n O
= O
5166 O
) O
, O
nationwide O
and O
age O
- O
standardized O
. O
The O
seroprevalence O
for O
C. O
burnetii O
for O
persons O
≥ O
15 O
years O
was O
estimated O
to O
be O
3.0 O
% O
( O
95 O
% O
CI O
2.2 O
- O
4.0 O
) O
, O
a O
level O
similar O
to O
national O
surveys O
from O
The O
Netherlands B-LOC
( O
2.4 O
% O
) O
and O
USA B-LOC
( O
3.1 O
% O
) O
, O
but O
lower O
than O
Australia B-LOC
( O
5.6 O
% O
) O
. O
A O
linear O
increase O
of O
C. O
burnetii O
seropositivity O
was O
associated O
with O
an O
individual O
's O
age O
, O
with O
the O
peak O
seroprevalence O
5.6 O
% O
( O
95 O
% O
CI O
3.6 O
- O
8.6 O
) O
observed O
in O
the O
≥65 O
years O
' O
group O
. O
C. O
burnetii O
seropositivity O
was O
significantly O
higher O
in O
the O
southern O
macro O
- O
zone O
6.0 O
% O
( O
95 O
% O
CI O
3.3 O
- O
10.6 O
) O
compared O
to O
metropolitan O
region O
1.8 O
% O
( O
95 O
% O
CI O
0.9 O
- O
3.3 O
) O
, O
the O
former O
region O
being O
home O
to O
significant O
livestock O
industries O
, O
particularly O
dairy O
farming O
. O
These O
data O
will O
be O
useful O
to O
inform O
targeted O
strategies O
for O
the O
prevention O
of O
Q O
fever O
in O
at O
- O
risk O
populations O
in O
Chile B-LOC
. O
Factor O
X O
deficiency O
is O
a O
severe O
inherited O
coagulation O
disorder O
, O
which O
is O
characterized O
by O
severe O
systemic O
bleeding O
manifestations O
in O
affected O
individuals O
. O
It O
is O
a O
rare O
disorder O
with O
a O
frequency O
of O
around B-STAT
1:1,000,000 I-STAT
in O
the O
general O
population O
. O
We O
present O
the O
case O
of O
an O
infant O
with O
factor O
X O
deficiency O
who O
presented O
with O
complex O
febrile O
seizure O
. O
Although O
febrile O
seizures O
are O
very O
common O
in O
children O
, O
a O
closer O
scrutiny O
leads O
to O
neuroimaging O
and O
finding O
of O
intracranial O
bleed O
. O
Hematologic O
and O
genetic O
investigations O
confirmed O
the O
diagnosis O
. O
A O
high O
index O
of O
suspicion O
should O
be O
maintained O
to O
diagnose O
uncommon O
bleeding O
disorders O
in O
children O
. O
BACKGROUND O
: O
Neonatal O
herpes O
simplex O
virus O
infection O
( O
nHSV O
) O
leads O
to O
severe O
morbidity O
and O
mortality O
, O
but O
national O
incidence B-EPI
is O
uncertain O
. O
Florida B-LOC
regulations O
require O
that O
healthcare O
providers O
report O
cases O
, O
and O
clinical O
laboratories O
report O
test O
results O
when O
herpes O
simplex O
virus O
( O
HSV O
) O
is O
detected O
. O
We O
estimated O
nHSV O
incidence B-EPI
using O
laboratory O
- O
confirmed O
provider O
- O
reported O
cases O
and O
electronic O
laboratory O
reports O
( O
ELR O
) O
stored O
separately O
from O
provider O
- O
reported O
cases O
. O
Mortality O
was O
estimated O
using O
provider O
- O
reported O
cases O
, O
ELR O
, O
and O
vital O
statistics O
death O
records O
. O
METHODS O
: O
For O
2011 O
- O
2017 O
, O
we O
reviewed O
: O
provider O
- O
reported O
cases O
( O
infants O
< O
60 O
days O
of O
age O
with O
HSV O
infection O
confirmed O
by O
culture O
or O
polymerase O
chain O
reaction O
( O
PCR O
) O
) O
, O
ELR O
of O
HSV O
- O
positive O
culture O
or O
PCR O
results O
in O
the O
same O
age O
group O
, O
and O
death O
certificates O
containing O
International O
Classification O
of O
Disease O
, O
Tenth O
Revision O
, O
codes O
for O
herpes O
infection O
: O
P35.2 O
, O
B00.0 O
- O
B00.9 O
, O
and O
A60.0 O
- O
A60.9 O
. O
Provider O
- O
reported O
cases O
were O
matched O
against O
ELR O
reports O
. O
Death O
certificates O
were O
matched O
with O
provider O
and O
ELR O
reports O
. O
Chapman O
's O
capture O
- O
recapture O
method O
was O
used O
to O
estimate O
nHSV O
incidence B-EPI
and O
mortality O
. O
Mortality O
from O
all O
three O
sources O
was O
estimated O
using O
log O
- O
linear O
modelling O
. O
RESULTS O
: O
Providers O
reported O
114 O
nHSV O
cases O
and O
ELR O
identified O
197 O
nHSV O
cases O
. O
Forty O
- O
six O
cases O
were O
common O
to O
both O
datasets O
, O
leaving O
265 O
unique O
nHSV O
reports O
. O
Chapman O
's O
estimate O
suggests O
483 B-STAT
( I-STAT
95 I-STAT
% I-STAT
C.I. O
383 O
- O
634 O
) O
nHSV O
cases O
occurred O
( O
31.5 B-STAT
infections I-STAT
per I-STAT
100,000 I-STAT
live I-STAT
births I-STAT
) O
. O
nHSV O
deaths O
were O
reported O
by O
providers O
( O
n=9 O
) O
, O
ELR O
( O
n=18 O
) O
, O
and O
vital O
statistics O
( O
n=31 O
) O
, O
totaling O
34 O
unique O
reports O
. O
Log O
- O
linear O
modeling O
estimates O
35.8 O
fatal O
cases O
occurred O
( O
95 O
% O
CI O
34 O
- O
40 O
) O
. O
CONCLUSIONS O
: O
Chapman O
's O
estimates O
using O
data O
collected O
over O
7 O
years O
in O
Florida B-LOC
, O
conclude O
nHSV O
infections O
occurred O
at O
a O
rate O
of O
1 B-STAT
per I-STAT
3000 I-STAT
live I-STAT
births I-STAT
. O
Background O
Congenital O
malformations O
are O
described O
in O
about O
3 O
% O
of O
live O
births O
and O
20 O
% O
of O
stillbirths O
in O
the O
industrialized O
countries O
. O
The O
prevalence B-EPI
of O
congenital O
anomalies O
in O
developing O
countries O
, O
including O
Morocco B-LOC
, O
is O
not O
well O
known O
at O
the O
national O
level O
. O
The O
aim O
of O
our O
study O
is O
to O
conduct O
a O
descriptive O
exploratory O
analysis O
of O
congenital O
malformations O
cases O
diagnosed O
at O
the O
O
Les O
Orangers O
O
Maternity O
and O
Reproductive O
Health O
Hospital O
in O
Rabat B-LOC
. O
Methods O
We O
collected O
all O
the O
cases O
of O
congenital O
malformations O
diagnosed O
at O
the O
O
Les O
Orangers O
O
Maternity O
and O
Reproductive O
Health O
Hospital O
in O
Rabat B-LOC
, O
from O
January O
1st O
, O
2011 O
to O
June O
31st O
, O
2016 O
. O
Data O
were O
reported O
on O
pre O
- O
established O
sheets O
and O
on O
a O
registry O
of O
malformations O
. O
Total O
and O
specific O
prevalences B-EPI
were O
calculated O
for O
each O
malformation O
. O
A O
principal O
component O
analysis O
( O
PCA O
) O
was O
then O
conducted O
followed O
by O
a O
Varimax O
rotation O
in O
order O
to O
identify O
the O
different O
associations O
of O
malformations O
in O
our O
series O
. O
Results O
We O
registred O
245 O
cases O
of O
congenital O
malformations O
out O
of O
a O
total O
of O
43,923 O
recorded O
births O
; O
a O
prevalence B-EPI
of O
5.58 B-STAT
per I-STAT
thousand I-STAT
births I-STAT
of O
which O
19.2 O
% O
were O
FDIU O
( O
fetal O
deaths O
in O
utero O
) O
. O
A O
polymalformative O
syndrome O
was O
found O
in O
26.5 O
% O
of O
cases O
which O
makes O
a O
total O
number O
of O
470 O
anomalies O
. O
The O
musculoskeletal O
anomalies O
predominate O
with O
a O
rate O
of O
33 O
% O
, O
followed O
by O
neurological O
abnormalities O
18 O
% O
, O
of O
whom O
31 O
% O
were O
hydrocephalus O
, O
26.2 O
% O
anencephaly O
, O
and O
20.24 O
% O
spina O
bifida O
. O
Malformations O
of O
the O
eye O
, O
ear O
, O
face O
and O
neck O
were O
described O
in O
12 O
% O
of O
the O
cases O
, O
while O
genetic O
abnormalities O
were O
observed O
in O
8,5 O
% O
of O
which O
87.5 O
% O
represented O
Down O
syndrome O
. O
The O
antenatal O
diagnosis O
of O
congenital O
malformations O
was O
performed O
in O
28.6 O
% O
of O
cases O
. O
Conclusions O
Our O
study O
provides O
a O
general O
overview O
of O
the O
epidemiological O
situation O
related O
to O
different O
types O
of O
congenital O
anomalies O
for O
a O
specific O
area O
in O
Morocco B-LOC
. O
It O
represents O
a O
database O
that O
should O
be O
complemented O
by O
other O
multicenter O
studies O
and O
the O
implementation O
of O
a O
national O
registry O
to O
determine O
the O
prevalence B-EPI
of O
congenital O
malformations O
at O
a O
national O
level O
. O
Hearing O
loss O
is O
one O
of O
the O
most O
common O
birth O
disorders O
in O
humans O
, O
with O
an O
estimated B-EPI
prevalence I-EPI
of O
1 B-STAT
- I-STAT
3 I-STAT
in O
every O
1000 O
newborns O
. O
This O
study O
investigates O
the O
molecular O
etiology O
of O
a O
hearing O
loss O
cohort O
using O
a O
stepwise O
strategy O
to O
effectively O
diagnose O
patients O
and O
address O
the O
challenges O
posed O
by O
the O
genetic O
heterogeneity O
and O
variable O
mutation O
spectrum O
of O
hearing O
loss O
. O
In O
order O
to O
target O
known O
pathogenic O
variants O
, O
multiplex O
PCR O
plus O
next O
- O
generation O
sequencing O
was O
applied O
in O
the O
first O
step O
; O
patients O
which O
did O
not O
receive O
a O
diagnosis O
from O
this O
were O
further O
referred O
for O
exome O
sequencing O
. O
A O
total O
of O
92 O
unrelated O
patients O
with O
nonsyndromic O
hearing O
loss O
were O
enrolled O
in O
the O
study O
. O
In O
total O
, O
64 O
% O
( O
59/92 O
) O
of O
the O
patients O
were O
molecularly O
diagnosed O
, O
44 O
of O
them O
in O
the O
first O
step O
by O
multiplex O
PCR O
plus O
sequencing O
. O
Exome O
sequencing O
resulted O
in O
eleven O
diagnoses O
( O
23 O
% O
, O
11/48 O
) O
and O
four O
probable O
diagnoses O
( O
8 O
% O
, O
4/48 O
) O
among O
the O
48 O
patients O
who O
were O
not O
diagnosed O
in O
the O
first O
step O
. O
The O
rate O
of O
secondary O
findings O
from O
exome O
sequencing O
in O
our O
cohort O
was O
3 O
% O
( O
2/58 O
) O
. O
This O
research O
presents O
a O
molecular O
diagnosis O
spectrum O
of O
92 O
non O
- O
syndromic O
hearing O
loss O
patients O
and O
demonstrates O
the O
benefits O
of O
using O
a O
stepwise O
diagnostic O
approach O
in O
the O
genetic O
testing O
of O
nonsyndromic O
hearing O
loss O
. O
This O
study O
aimed O
to O
analyze O
the O
epidemiology O
of O
congenital O
upper O
limb O
anomalies O
( O
CULA O
) O
in O
Korea B-LOC
. O
We O
evaluated O
the O
incidence B-EPI
of O
each O
type O
of O
CULA O
, O
the O
presence O
of O
coexisting O
anomalies O
and O
the O
surgical O
treatment O
status O
in O
CULA O
patients O
. O
We O
conducted O
a O
retrospective O
cohort O
study O
of O
patients O
aged O
< B-STAT
1 I-STAT
year I-STAT
between I-STAT
2007 I-STAT
and O
2016 O
who O
were O
registered O
with O
CULA O
in O
the O
Health O
Insurance O
Review O
and O
Assessment O
Service O
of O
Korea O
. O
In O
total O
, O
10,704 O
patients O
had O
CULA O
, O
including O
6,174 O
boys O
( O
57.7 O
% O
) O
and O
4,530 O
girls O
( O
42.3 O
% O
) O
. O
The O
mean O
annual B-EPI
incidence I-EPI
of O
CULA O
was O
23.5 B-STAT
per I-STAT
10,000 I-STAT
live I-STAT
births I-STAT
; O
it O
was O
significantly O
higher O
in O
boys O
than O
in O
girls O
( O
26.3 O
vs. O
20.5 O
, O
p O
< O
0.001 O
) O
. O
Among O
the O
four O
categories O
of O
CULA O
- O
polydactyly O
, O
syndactyly O
, O
limb O
deficiency O
, O
and O
other O
anomalies O
- O
polydactyly O
was O
the O
most O
common O
. O
In O
total O
, O
4,149 O
patients O
( O
38.8 O
% O
) O
had O
other O
congenital O
anomalies O
and O
coexisting O
anomalies O
of O
the O
circulatory O
system O
( O
24.9 O
% O
) O
were O
the O
most O
common O
. O
In O
total O
4,776 O
patients O
( O
44.6 O
% O
) O
underwent O
operative O
treatment O
for O
CULA O
within O
minimum O
three O
years O
of O
the O
diagnosis O
. O
The O
proportion O
of O
patients O
who O
underwent O
surgical O
treatment O
was O
significantly O
higher O
for O
polydactyly O
( O
73.4 O
% O
vs. O
16.8 O
% O
, O
p O
< O
0.001 O
) O
and O
syndactyly O
( O
65.3 O
% O
vs. O
41.5 O
% O
, O
p O
< O
0.001 O
) O
, O
but O
it O
was O
significantly O
lower O
in O
limb O
deficiency O
( O
27.6 O
% O
vs. O
45.4 O
% O
, O
p O
< O
0.001 O
) O
and O
other O
anomalies O
( O
10.0 O
% O
vs. O
69.8 O
% O
, O
p O
< O
0.001 O
) O
than O
rest O
of O
CULA O
patients O
. O
Among O
the O
patients O
who O
had O
operations O
, O
21.5 O
% O
underwent O
multiple O
operations O
. O
The O
proportion O
of O
patients O
who O
underwent O
multiple O
operations O
was O
significantly O
higher O
in O
syndactyly O
( O
35.6 O
% O
vs. O
18.1 O
% O
, O
p O
< O
0.001 O
) O
, O
but O
it O
was O
significantly O
lower O
in O
polydactyly O
( O
4.0 O
% O
vs. O
95.5 O
% O
, O
p O
< O
0.001 O
) O
and O
other O
anomalies O
( O
17.9 O
% O
vs. O
21.9 O
% O
, O
p O
< O
0.001 O
) O
than O
rest O
of O
CULA O
patients O
. O
These O
results O
could O
provide O
a O
basis O
for O
estimating O
the O
national O
healthcare O
costs O
for O
CULA O
and O
the O
required O
number O
of O
CULA O
specialists O
. O
The O
Australian O
Cattle O
dog O
( O
ACD O
) O
is O
one O
of O
many O
breeds O
predisposed O
to O
congenital O
sensorineural O
deafness O
( O
CSD O
) O
. O
The O
objective O
of O
this O
study O
was O
to O
estimate O
CSD O
prevalence B-EPI
and O
investigate O
any O
association O
with O
phenotype O
in O
the O
ACD O
in O
the O
UK B-LOC
. O
The O
database O
of O
the O
authors O
' O
institution O
was O
searched O
for O
ACD O
puppies O
undergoing O
brainstem O
auditory O
evoked O
response O
( O
BAER O
) O
testing O
for O
CSD O
screening O
( O
1999 O
- O
2019 O
) O
. O
Inclusion O
criteria O
were O
BAER O
performed O
at O
4 O
- O
10 O
weeks O
of O
age O
, O
testing O
of O
complete O
litters O
and O
available O
phenotypic O
data O
. O
The O
age O
, O
sex O
, O
coat O
and O
iris O
colour O
, O
presence O
and O
location O
of O
face O
and O
body O
patches O
, O
hearing O
status O
and O
BAER- O
determined O
parental O
hearing O
status O
of O
each O
puppy O
were O
recorded O
. O
A O
multivariable O
mixed O
- O
effects O
logistic O
regression O
model O
was O
used O
to O
calculate O
odds O
ratios O
and O
95 O
% O
confidence O
intervals O
to O
determine O
whether O
any O
of O
these O
variables O
were O
significantly O
associated O
with O
CSD O
, O
while O
adjusting O
for O
clustering O
at O
litter O
level O
. O
Inclusion O
criteria O
were O
met O
for O
524 O
puppies O
. O
Hearing O
was O
bilaterally O
normal O
in O
464 O
puppies O
( O
88.6 O
% O
) O
. O
The O
prevalence B-EPI
of O
unilateral O
and O
bilateral O
CSD O
was O
9.7 O
% O
and O
1.7 O
% O
, O
respectively O
. O
On O
the O
basis O
of O
multivariable O
analysis O
, O
the O
presence O
of O
a O
pigmented O
face O
patch O
was O
the O
only O
phenotypic O
variable O
significantly O
associated O
with O
CSD O
, O
and O
was O
linked O
to O
a O
reduced O
risk O
of O
the O
condition O
. O
The O
prevalence B-EPI
was O
similar O
to O
that O
reported O
in O
an O
Australian O
population O
of O
ACDs O
. O
The O
key O
findings O
from O
this O
study O
were O
that O
overall O
CSD O
prevalence B-EPI
in O
the O
ACD O
population O
in O
the O
UK B-LOC
was O
11.4 O
% O
, O
and O
puppies O
with O
a O
face O
patch O
were O
at O
reduced O
risk O
of O
the O
condition O
. O
Background O
The O
evidence O
of O
an O
association O
between O
statins O
and O
amyotrophic O
lateral O
sclerosis O
( O
ALS O
) O
is O
heterogeneous O
and O
inconclusive O
. O
Methods O
We O
performed O
a O
population O
- O
based O
cohort O
study O
consisting O
of O
974,304 O
statin O
initiators O
aged O
≥40 O
years O
and O
1,948,606 O
matched O
general O
population O
comparators O
identified O
from O
Danish O
, O
nationwide O
registries O
( O
1996 O
- O
2016 O
) O
. O
We O
computed O
incidence B-EPI
rates O
and O
hazard O
ratios O
( O
HRs O
) O
of O
a O
first O
- O
time O
hospital O
- O
based O
diagnosis O
of O
ALS O
. O
HRs O
were O
controlled O
for O
sex O
, O
birth O
year O
, O
calendar O
year O
, O
medically O
diagnosed O
comorbidities O
, O
and O
concomitant O
medications O
. O
Results O
During O
a O
median O
follow O
- O
up O
of O
7.7 O
years O
, O
852 O
ALS O
events O
occurred O
among O
statin O
initiators O
( O
11.3 O
[ O
95 O
% O
CI O
: O
10.6 O
- O
12.1 O
] O
events B-STAT
per I-STAT
100,000 I-STAT
person I-STAT
- O
years O
) O
and O
1,679 O
among O
non O
- O
initiators O
( O
11.4 O
[ O
95 O
% O
CI O
: O
10.9 O
- O
12.0 O
] O
events B-STAT
per I-STAT
100,000 I-STAT
person I-STAT
- O
years O
) O
. O
The O
overall O
adjusted O
HR O
indicated O
a O
slight O
association O
between O
statin O
initiation O
and O
ALS O
( O
1.11 O
[ O
95 O
% O
CI O
: O
1.00 O
- O
1.23 O
] O
. O
In O
the O
first O
year O
after O
initiation O
, O
the O
HR O
was O
1.40 O
( O
95 O
% O
CI O
: O
1.09 O
- O
1.79 O
) O
for O
both O
sexes O
combined O
, O
1.00 O
( O
95 O
% O
CI O
: O
0.70 O
- O
1.42 O
) O
for O
men O
, O
and O
1.92 O
( O
95 O
% O
CI O
: O
1.30 O
- O
2.82 O
) O
for O
women O
. O
The O
associations O
diminished O
to O
approximately O
null O
after O
the O
first O
year O
of O
follow O
- O
up O
for O
both O
sexes O
combined O
and O
for O
men O
, O
but O
point O
estimates O
were O
above O
1 O
for O
women O
until O
10 O
years O
after O
initiation O
. O
Conclusions O
Statin O
initiation O
was O
largely O
unassociated O
with O
ALS O
diagnosis O
but O
was O
associated O
with O
an O
elevated O
risk O
of O
ALS O
in O
women O
, O
especially O
in O
the O
first O
year O
after O
initiation O
. O
The O
association O
could O
be O
explained O
by O
reverse O
causation O
, O
detection O
bias O
, O
early O
neurotoxic O
effects O
of O
statins O
that O
affect O
women O
more O
than O
men O
, O
or O
a O
combination O
thereof O
. O
Papillon O
- O
Lefevre O
syndrome O
( O
PLS O
) O
is O
a O
rare O
disease O
characterized O
by O
skin O
lesions O
, O
which O
includes O
palmar O
- O
plantar O
hyperkeratosis O
and O
hyperhidrosis O
with O
severe O
periodontal O
destruction O
involving O
both O
the O
primary O
and O
the O
permanent O
dentitions O
. O
It O
is O
transmitted O
as O
an O
autosomal O
- O
recessive O
condition O
, O
and O
consanguinity O
of O
parents O
is O
evident O
in O
about O
one O
- O
third O
of O
the O
cases O
. O
This O
paper O
describes O
a O
13 O
- O
year O
- O
old O
male O
patient O
who O
presented O
to O
the O
department O
of O
pedodontics O
, O
with O
rapidly O
progressing O
periodontitis O
. O
A O
general O
physical O
examination O
revealed O
scaling O
on O
the O
hands O
and O
feet O
, O
which O
had O
been O
medically O
diagnosed O
as O
PLS O
. O
The O
incidence B-EPI
of O
this O
rare O
entity O
is O
increasing O
in O
the O
recent O
times O
, O
which O
is O
associated O
with O
irreparable O
periodontal O
destruction O
at O
an O
early O
age O
, O
with O
not O
so O
prominent O
skin O
lesions O
in O
some O
cases O
. O
In O
such O
instances O
, O
the O
dentist O
has O
a O
more O
important O
role O
in O
diagnosing O
, O
treatment O
planning O
and O
preservation O
of O
the O
periodontal O
tissues O
and O
, O
at O
the O
same O
time O
, O
referring O
for O
the O
treatment O
of O
the O
skin O
lesions O
. O
This O
paper O
emphasizes O
the O
combined O
effort O
of O
the O
two O
specialities O
in O
order O
to O
maintain O
skin O
as O
well O
as O
dental O
conditions O
in O
health O
by O
early O
intervention O
and O
a O
synergistic O
treatment O
approach O
. O
OBJECTIVES O
: O
To O
describe O
the O
prevalence B-EPI
of O
the O
reduced O
ankle O
- O
brachial O
index O
( O
ABI O
) O
in O
patients O
with O
heart O
failure O
( O
HF O
) O
with O
preserved O
ejection O
fraction O
( O
HFpEF O
) O
attended O
at O
a O
HF O
clinic O
in O
the O
metropolitan O
region O
of O
Porto B-LOC
Alegre I-LOC
, O
and O
to O
compar O
the O
patients O
to O
those O
with O
reduced O
ejection O
fraction O
( O
HFrEF O
) O
. O
METHODS O
: O
A O
descriptive O
observational O
study O
, O
included O
patients O
referred O
to O
the O
heart O
failure O
clinic O
in O
HU O
- O
Ulbra O
with O
HFpEF O
or O
HFrEF O
and O
diastolic O
dysfunction O
, O
and O
measurements O
of O
ABIs O
using O
vascular O
Doppler O
equipment O
were O
performed O
in O
both O
groups O
. O
RESULTS O
: O
The O
sample O
consisted O
of O
106 O
patients O
with O
HF O
, O
53.9 O
% O
of O
the O
patients O
had O
HFpEF O
, O
and O
19.4 O
% O
had O
a O
diagnosis O
of O
peripheral O
arterial O
disease O
( O
PAD O
) O
( O
ABI O
less O
than O
0.9 O
) O
. O
PAD O
was O
identified O
in O
24.1 O
% O
of O
the O
patients O
with O
HFpEF O
, O
while15.8 O
% O
of O
patients O
in O
the O
HFrEF O
group O
were O
diagnosed O
with O
PAD O
. O
CONCLUSION O
: O
Our O
results O
did O
not O
identify O
a O
significantly O
different O
prevalence B-EPI
of O
altered O
and O
compatible O
PAD O
values O
in O
patients O
with O
HFpEF O
. O
However O
, O
we O
showed O
a O
prevalence B-EPI
of O
19.4 O
% O
, O
a O
high O
value O
if O
we O
consider O
similar O
populations O
. O
Enamel O
renal O
syndrome O
is O
a O
unique O
syndrome O
associated O
with O
kidney O
agenesis O
associated O
with O
kidney O
agenesis O
, O
amelogenesis O
imperfecta O
, O
and O
gingival O
hyperplasia O
. O
The O
prevalence B-EPI
rate O
of O
this O
rare O
syndrome O
is O
< B-STAT
1/1,000,000 I-STAT
. O
A O
17 O
- O
year O
- O
old O
male O
patient O
came O
to O
the O
department O
of O
periodontics O
, O
with O
a O
chief O
complaint O
of O
dislodged O
crown O
in O
the O
anterior O
teeth O
region O
. O
On O
clinical O
examination O
, O
the O
patient O
had O
teeth O
with O
mottled O
enamel O
and O
gingival O
enlargement O
. O
The O
orthopantomograph O
and O
gingival O
biopsy O
revealed O
pulpal O
calcification O
and O
gingival O
calcification O
, O
respectively O
. O
Furthermore O
, O
the O
renal O
ultrasonography O
revealed O
absence O
/ O
agenesis O
of O
the O
left O
kidney O
. O
Thus O
, O
based O
on O
radiographical O
, O
histological O
, O
and O
ultrasound O
investigations O
, O
the O
patient O
was O
diagnosed O
with O
nephrocalcinosis O
syndrome O
. O
The O
patient O
was O
treated O
with O
periodontal O
therapy O
and O
prosthodontic O
full O
- O
mouth O
rehabilitation O
. O
This O
case O
report O
highlights O
the O
need O
of O
a O
periodontist O
to O
be O
acquainted O
about O
the O
signs O
and O
symptoms O
of O
the O
syndrome O
to O
benefit O
an O
individual O
in O
the O
right O
diagnosis O
and O
treatment O
plan O
. O
Mitochondria O
are O
ubiquitous O
intracellular O
organelles O
found O
in O
almost O
all O
eukaryotes O
and O
involved O
in O
various O
aspects O
of O
cellular O
life O
, O
with O
a O
primary O
role O
in O
energy O
production O
. O
The O
interest O
in O
this O
organelle O
has O
grown O
stronger O
with O
the O
discovery O
of O
their O
link O
to O
various O
pathologies O
, O
including O
cancer O
, O
aging O
and O
neurodegenerative O
diseases O
. O
Indeed O
, O
dysfunctional O
mitochondria O
can O
not O
provide O
the O
required O
energy O
to O
tissues O
with O
a O
high O
- O
energy O
demand O
, O
such O
as O
heart O
, O
brain O
and O
muscles O
, O
leading O
to O
a O
large O
spectrum O
of O
clinical O
phenotypes O
. O
Mitochondrial O
defects O
are O
at O
the O
origin O
of O
a O
group O
of O
clinically O
heterogeneous O
pathologies O
, O
called O
mitochondrial O
diseases O
, O
with O
an O
incidence B-EPI
of O
1 B-STAT
in I-STAT
5000 I-STAT
live I-STAT
births I-STAT
. O
Primary O
mitochondrial O
diseases O
are O
associated O
with O
genetic O
mutations O
both O
in O
nuclear O
and O
mitochondrial O
DNA O
( O
mtDNA O
) O
, O
affecting O
genes O
involved O
in O
every O
aspect O
of O
the O
organelle O
function O
. O
As O
a O
consequence O
, O
it O
is O
difficult O
to O
find O
a O
common O
cause O
for O
mitochondrial O
diseases O
and O
, O
subsequently O
, O
to O
offer O
a O
precise O
clinical O
definition O
of O
the O
pathology O
. O
Moreover O
, O
the O
complexity O
of O
this O
condition O
makes O
it O
challenging O
to O
identify O
possible O
therapies O
or O
drug O
targets O
. O
Although O
many O
nutritional O
deficiencies O
are O
associated O
with O
Crohn O
's O
disease O
( O
CD O
) O
, O
vitamin O
C O
deficiency O
is O
less O
frequently O
diagnosed O
and O
reported O
despite O
its O
prevalence B-EPI
. O
Vitamin O
C O
deficiency O
may O
be O
more O
difficult O
to O
diagnose O
in O
patients O
with O
CD O
because O
symptoms O
from O
active O
CD O
may O
overlap O
with O
scurvy O
. O
Identification O
of O
the O
deficiency O
is O
vital O
, O
however O
, O
because O
treatment O
can O
lead O
to O
swift O
, O
marked O
resolution O
of O
symptoms O
. O
We O
present O
a O
patient O
with O
long O
- O
standing O
CD O
who O
presented O
with O
gum O
bleeding O
and O
was O
found O
to O
have O
scurvy O
. O
Purpose O
: O
Cataract O
surgery O
, O
quantity O
and O
quality O
, O
is O
an O
indicator O
of O
ophthalmic O
care O
. O
A O
comprehensive O
assessment O
of O
cataract O
surgical O
services O
has O
never O
been O
carried O
out O
in O
Palestine B-LOC
, O
including O
West B-LOC
Bank I-LOC
, O
Gaza B-LOC
Strip I-LOC
and O
East B-LOC
Jerusalem I-LOC
. O
The O
objective O
of O
this O
study O
was O
to O
estimate O
the O
cataract O
surgical O
rate O
in O
2015 O
to O
and O
to O
explore O
the O
modes O
of O
payment O
and O
referral O
systems O
. O
Methods O
: O
A O
cross O
- O
sectional O
study O
conducted O
between O
June O
and O
August O
2016 O
. O
Medical O
Directors O
from O
Cataract O
Surgical O
Centres O
in O
Palestine B-LOC
were O
interviewed O
using O
a O
structured O
questionnaire O
to O
extract O
data O
on O
cataract O
output O
and O
surgical O
techniques O
. O
Additionally O
, O
data O
were O
collected O
on O
modes O
of O
payment O
for O
cataract O
services O
. O
The O
cataract O
surgical O
rate O
was O
calculated O
by O
dividing O
the O
total O
cataract O
output O
in O
2015 O
by O
the O
estimated O
population O
of O
Palestine B-LOC
in O
millions O
. O
Results O
: O
In O
2015 O
, O
9908 O
cataract O
surgeries O
were O
carried O
out O
in O
22 O
centres O
. O
The O
cataract O
surgical O
rate O
was O
2,117 B-STAT
operations I-STAT
per I-STAT
million I-STAT
population I-STAT
. O
Phacoemulsification O
was O
the O
most O
common O
technique O
( O
73.4 O
% O
) O
, O
however O
in O
government O
centres O
67 O
% O
were O
performed O
by O
extracapsular O
cataract O
extraction O
. O
In O
the B-LOC
Gaza I-LOC
Strip I-LOC
, O
56.6 O
% O
of O
cataract O
surgeries O
were O
operated O
at O
government O
centres O
, O
and O
42.8 O
% O
were O
operated O
at O
NGO B-LOC
centres O
while O
in O
West B-LOC
Bank I-LOC
, O
only O
12 O
% O
of O
cataract O
surgeries O
were O
operated O
at O
government O
centres O
, O
with O
two O
- O
thirds O
of O
cataracts O
diagnosed O
at O
governmental O
centres O
being O
referred O
to O
private O
and O
NGO B-LOC
centres O
. O
Seventy O
eight O
percent O
of O
cataract O
surgeries O
were O
funded O
by O
insurance O
, O
of O
which O
the O
government O
insurance O
scheme O
contributed O
65 B-STAT
% I-STAT
. O
Conclusion O
: O
The O
cataract O
surgical O
rate O
in O
Palestine B-LOC
falls O
short O
of O
the O
required O
WHO O
target O
. O
The O
majority O
of O
cataract O
surgeries O
are O
funded O
by O
insurance O
. O
BACKGROUND O
: O
Most O
patients O
with O
isolated O
methylmalonic O
acidemia O
( O
MMA O
) O
/propionic O
acidemia O
( O
PA O
) O
presenting O
during O
the O
neonatal O
period O
with O
acute O
metabolic O
distress O
are O
at O
risk O
for O
death O
and O
significant O
neurodevelopmental O
disability O
. O
The O
nationwide O
newborn O
screening O
for O
MMA O
/ O
PA O
has O
been O
in O
place O
in O
Taiwan B-LOC
from O
January O
, O
2000 O
and O
data O
was O
collected O
until O
December O
, O
2016 O
. O
RESULTS O
: O
During O
the O
study O
period O
, O
3,155,263 O
newborns O
were O
screened O
. O
The O
overall B-EPI
incidence I-EPI
of O
MMA O
mutase O
type O
cases O
was O
1/121,356 B-STAT
( O
n O
= O
26 O
) O
, O
1 B-STAT
cobalamin I-STAT
B I-STAT
was O
detected O
and O
that O
for O
PA O
cases O
( O
n O
= O
4 O
) O
was O
1/788,816 B-STAT
. O
The O
time O
of O
referral O
is O
8.8 O
days O
for O
MMA O
patients O
, O
and O
7.5 O
days O
for O
PA O
patients O
. O
The O
MMA O
mutase O
type O
patients O
have O
higher O
AST O
, O
ALT O
, O
and O
NH3 O
values O
as O
well O
as O
a O
lower O
pH O
value O
( O
p O
< O
0.05 O
) O
. O
The O
mean O
age O
for O
liver O
transplantation O
( O
LT O
) O
is O
402 O
days O
( O
range O
from O
0.6 O
- O
6.7 O
yr O
) O
with O
16 O
out O
of O
20 O
cases O
( O
80.0 O
% O
) O
using O
living O
donors O
. O
The O
mean O
admission O
length O
shortened O
from O
90.6 O
days O
/ O
year O
( O
pre O
- O
LT O
) O
to O
5.3 O
days O
/ O
year O
( O
at O
3rd O
year O
post O
- O
LT O
) O
( O
p O
< O
0.0005 O
) O
. O
Similarly O
, O
the O
tube O
feeding O
ratio O
decreased O
from O
67.8 B-STAT
to I-STAT
0.50 I-STAT
% I-STAT
( O
p O
< O
0.00005 O
) O
. O
The O
anxiety O
level O
of O
the O
caregiver O
was O
reduced O
from O
33.4 O
to O
27.2 O
after O
LT O
( O
p O
= O
0.001 O
) O
and O
the O
DQ O
/ O
IQ O
performance O
of O
the O
patients O
was O
improved O
after O
LT O
from O
50 O
to O
60.1 O
( O
p O
= O
0.07 O
) O
. O
CONCLUSION O
: O
MMA O
/ O
PA O
patients O
with O
LT O
do O
survive O
and O
have O
reduced O
admission O
time O
, O
reduced O
tube O
feeding O
and O
the O
caregiver O
is O
less O
anxious O
. O
The O
use O
of O
Drosophila O
melanogaster O
as O
a O
model O
for O
studying O
human O
disease O
is O
well O
established O
, O
reflected O
by O
the O
steady O
increase O
in O
both O
the O
number O
and O
proportion O
of O
fly O
papers O
describing O
human O
disease O
models O
in O
recent O
years O
. O
In O
this O
article O
, O
we O
highlight O
recent O
efforts O
to O
improve O
the O
availability O
and O
accessibility O
of O
the O
disease O
model O
information O
in O
FlyBase O
( O
http://flybase.org O
) O
, O
the O
model O
organism O
database O
for O
Drosophila O
. O
FlyBase O
has O
recently O
introduced O
Human O
Disease O
Model O
Reports O
, O
each O
of O
which O
presents O
background O
information O
on O
a O
specific O
disease O
, O
a O
tabulation O
of O
related O
disease O
subtypes O
, O
and O
summaries O
of O
experimental O
data O
and O
results O
using O
fruit O
flies O
. O
Integrated O
presentations O
of O
relevant O
data O
and O
reagents O
described O
in O
other O
sections O
of O
FlyBase O
are O
incorporated O
into O
these O
reports O
, O
which O
are O
specifically O
designed O
to O
be O
accessible O
to O
non O
- O
fly O
researchers O
in O
order O
to O
promote O
collaboration O
across O
model O
organism O
communities O
working O
in O
translational O
science O
. O
Another O
key O
component O
of O
disease O
model O
information O
in O
FlyBase O
is O
that O
data O
are O
collected O
in O
a O
consistent O
format O
--- O
using O
the O
evolving O
Disease O
Ontology O
( O
an O
open O
- O
source O
standardized O
ontology O
for O
human O
- O
disease O
- O
associated O
biomedical O
data O
) O
- O
to O
allow O
robust O
and O
intuitive O
searches O
. O
To O
facilitate O
this O
, O
FlyBase O
has O
developed O
a O
dedicated O
tool O
for O
querying O
and O
navigating O
relevant O
data O
, O
which O
include O
mutations O
that O
model O
a O
disease O
and O
any O
associated O
interacting O
modifiers O
. O
In O
this O
article O
, O
we O
describe O
how O
data O
related O
to O
fly O
models O
of O
human O
disease O
are O
presented O
in O
individual O
Gene O
Reports O
and O
in O
the O
Human O
Disease O
Model O
Reports O
. O
Finally O
, O
we O
discuss O
search O
strategies O
and O
new O
query O
tools O
that O
are O
available O
to O
access O
the O
disease O
model O
data O
in O
FlyBase O
. O
Seizures O
are O
the O
most O
acute O
evident O
manifestation O
of O
central O
nervous O
system O
dysfunction O
in O
neonates O
. O
The O
incidence B-EPI
is O
higher O
in O
very O
low O
weight O
neonates O
, O
about O
58/100 B-STAT
live I-STAT
births I-STAT
, O
as O
opposed O
to O
full O
- O
term O
infants O
, O
estimated O
about O
3.5/100 B-STAT
live I-STAT
births I-STAT
. O
Neonatal O
seizures O
represent O
the O
clinical O
manifestation O
of O
a O
non O
- O
specific O
disorder O
of O
cortical O
cerebral O
dysfunction O
, O
which O
could O
lead O
to O
permanent O
brain O
injury O
. O
The O
etiology O
is O
multifactorial O
and O
requires O
a O
judicious O
assessment O
of O
each O
clinical O
scenario O
. O
The O
diagnosis O
and O
its O
management O
are O
further O
complicated O
as O
most O
neonatal O
seizures O
may O
have O
very O
subtle O
or O
no O
clinical O
changes O
and O
the O
diagnosis O
may O
be O
just O
based O
on O
EEG O
findings O
, O
so O
- O
called O
subclinical O
. O
The O
treatment O
is O
dependent O
on O
the O
etiology O
, O
but O
early O
and O
opportune O
intervention O
can O
prevent O
further O
brain O
damage O
and O
improve O
prognosis O
. O
Although O
early O
identification O
and O
treatment O
are O
essential O
, O
the O
diagnosis O
of O
neonatal O
seizures O
can O
be O
further O
complicated O
by O
the O
clinical O
presentations O
, O
possible O
etiologies O
, O
and O
treatments O
. O
Nevertheless O
, O
research O
studies O
and O
clinical O
evidence O
have O
shown O
that O
early O
treatment O
with O
anti O
- O
seizure O
medications O
can O
change O
the O
outcome O
. O
Urea O
cycle O
disorders O
( O
UCDs O
) O
are O
inherited O
metabolic O
disorders O
with O
impaired O
nitrogen O
detoxification O
caused O
by O
defects O
in O
urea O
cycle O
enzymes O
. O
They O
often O
manifest O
with O
hyperammonemic O
attacks O
resulting O
in O
significant O
morbidity O
or O
death O
. O
We O
performed O
a O
nationwide O
questionnaire O
- O
based O
study O
between O
January O
2000 O
and O
March O
2018 O
to O
document O
all O
UCDs O
in O
Japan B-LOC
, O
including O
diagnoses O
, O
treatments O
, O
and O
outcomes O
. O
A O
total O
of O
229 O
patients O
with O
UCDs O
were O
enrolled O
in O
this O
study O
: O
73 O
males O
and O
53 O
females O
with O
ornithine O
transcarbamylase O
deficiency O
( O
OTCD O
) O
, O
33 O
patients O
with O
carbamoylphosphate O
synthetase O
1 B-STAT
deficiency I-STAT
, I-STAT
48 I-STAT
with O
argininosuccinate O
synthetase O
deficiency O
, O
14 O
with O
argininosuccinate O
lyase O
deficiency O
, O
and O
8 O
with O
arginase O
deficiency O
. O
Survival O
rates O
at O
20 O
years O
of O
age O
of O
male O
and O
female O
patients O
with O
late O
- O
onset O
OTCD O
were O
100 O
% O
and O
97.7 O
% O
, O
respectively O
. O
Blood O
ammonia O
levels O
and O
time O
of O
onset O
had O
a O
significant O
impact O
on O
the O
neurodevelopmental O
outcome O
( O
P O
< O
.001 O
and O
P O
= O
.028 O
, O
respectively O
) O
. O
Hemodialysis O
and O
liver O
transplantation O
did O
not O
prevent O
poor O
neurodevelopmental O
outcomes O
. O
While O
treatment O
including O
medication O
, O
hemodialysis O
, O
and O
liver O
transplantation O
may O
aid O
in O
decreasing O
blood O
ammonia O
and/or O
preventing O
severe O
hyperammonemia O
, O
a O
blood O
ammonia O
level O
≥ O
360 O
μmol O
/ O
L O
was O
found O
to O
be O
a O
significant O
indicator O
for O
a O
poor O
neurodevelopmental O
outcome O
. O
In O
conclusion O
, O
although O
current O
therapy O
for O
UCDs O
has O
advanced O
and O
helped O
saving O
lives O
, O
patients O
with O
blood O
ammonia O
levels O
≥ O
360 O
μmol O
/ O
L O
at O
onset O
often O
have O
impaired O
neurodevelopmental O
outcomes O
. O
Novel O
neuroprotective O
measures O
should O
therefore O
be O
developed O
to O
achieve O
better O
neurodevelopmental O
outcomes O
in O
these O
patients O
. O
Despite O
the O
importance O
of O
Culex O
species O
as O
major O
vectors O
of O
Rift B-LOC
Valley I-LOC
fever O
virus O
, O
West B-LOC
Nile I-LOC
virus O
and O
the O
microfilariae O
that O
cause O
lymphatic O
filariasis O
, O
information O
on O
these O
mosquitoes O
in O
Sudan B-LOC
is O
limited O
to O
works O
published O
65 O
years O
ago O
in O
the O
former O
Anglo O
- O
Egyptian O
Sudan B-LOC
, O
where O
some O
species O
were O
only O
recorded O
from O
areas O
of O
the O
territory O
now O
known O
as O
South B-LOC
Sudan I-LOC
. O
In O
this O
paper O
, O
we O
provide O
updated O
information O
on O
Culex O
mosquitoes O
collected O
indoors O
during O
surveillance O
studies O
conducted O
along O
the B-LOC
Nile I-LOC
River I-LOC
in O
central O
and O
northern O
areas O
of O
Sudan B-LOC
between O
2012 O
and O
2019 O
. O
Of O
3,411 O
female O
mosquitoes O
collected O
in O
Khartoum B-LOC
and O
northern O
states O
along O
the O
river O
, O
2,560 O
( O
75 O
% O
) O
were O
specimens O
of O
Culex O
belonging O
to O
12 O
species O
: O
Cx O
. O
( O
Culex O
) O
antennatus O
( O
Becker O
, O
1903 O
) O
, O
Cx O
. O
( O
Cux O
. O
) O
laticinctus O
Edwards O
, O
1913 O
, O
Cx O
. O
( O
Cux O
. O
) O
neavei O
Theobald B-LOC
, O
1906 O
, O
Cx O
. O
( O
Cux O
. O
) O
pipiens O
Linnaeus O
, O
1758 O
, O
Cx O
. O
( O
Cux O
. O
) O
perexiguus O
Theobald B-LOC
, O
1903 O
, O
Cx O
. O
( O
Cux O
. O
) O
poicilipes O
( O
Theobald B-LOC
, O
1903 O
) O
, O
Cx O
. O
( O
Cux O
. O
) O
quinquefasciatus O
Say O
, O
1823 O
, O
Cx O
. O
( O
Cux O
. O
) O
simpsoni O
Theobald B-LOC
, O
1905 O
, O
Cx O
. O
( O
Cux O
. O
) O
sinaiticus O
Kirkpatrick O
, O
1925 O
, O
Cx O
. O
( O
Cux O
. O
) O
theileri O
Theobald B-LOC
, O
1903 O
, O
Cx O
. O
( O
Cux O
. O
) O
tritaeniorhynchus O
Giles O
, O
1901 O
and O
Cx O
. O
( O
Culiciomyia O
) O
macfiei O
Edwards O
, O
1923 O
. O
This O
is O
the O
first O
record O
for O
Cx O
. O
tritaeniorhynchus O
and O
Cx O
. O
macfiei O
in O
central O
Sudan B-LOC
. O
The O
relative O
abundance O
of O
each O
species O
varied O
in O
different O
areas O
and O
seasons O
, O
but O
Cx O
. O
antennatus O
and O
Cx O
. O
quinquefasciatus O
were O
the O
most O
abundant O
indoor O
resting O
species O
. O
We O
provide O
an O
updated O
dichotomous O
key O
for O
the O
identification O
of O
the O
adults O
of O
Culex O
mosquitoes O
known O
to O
occur O
in O
the B-LOC
Republic I-LOC
of I-LOC
the I-LOC
Sudan I-LOC
. O
The O
authors O
analyse O
descriptions O
of O
Greenlandic O
and O
Faroese O
medicine O
found O
in O
an O
Italian O
medical O
publication O
from O
the O
18th O
century O
entitled O
, O
Europae O
Medicina O
a O
Sapientibus O
Illustrata O
[ O
… O
] O
, O
which O
was O
printed O
in O
Brescia B-LOC
, O
in O
Northern B-LOC
Italy I-LOC
, O
in O
1747 O
. O
The O
author O
of O
these O
descriptions O
, O
Francesco O
Roncalli O
Parolino O
( O
1692 O
- O
1769 O
) O
, O
was O
a O
renowned O
European O
physician O
. O
Roncalli O
Parolino O
focused O
his O
study O
on O
the O
treatment O
of O
scurvy O
and O
he O
promoted O
the O
inclusion O
of O
the O
Greenlandic O
and O
Faroese O
therapy O
into O
the O
broader O
European O
context O
. O
He O
was O
influenced O
to O
do O
this O
due O
to O
the O
already O
integrated O
European O
perspective O
of O
medicine O
which O
his O
book O
follows O
. O
Like O
now O
, O
medicine O
in O
18th O
- O
century O
Europe B-LOC
was O
multicentric O
and O
characterised O
by O
rich O
intellectual O
activity O
, O
which O
contributed O
to O
the O
enhancement O
of O
clinical O
practice O
during O
this O
period O
. O
At O
the O
time O
, O
Greenland B-LOC
and O
Faroe B-LOC
Islands I-LOC
were O
also O
integrated O
into O
this O
European O
context O
because O
they O
contributed O
for O
medical O
- O
scientific O
development O
that O
would O
lay O
the O
foundations O
for O
modern O
medicine O
. O
Francesco O
Roncalli O
Parolino O
obtained O
just O
recognition O
for O
these O
regions O
through O
the O
advancement O
and O
defence O
of O
their O
valuable O
medical O
contributions O
. O
VACTERL O
/ O
VATER O
association O
is O
typically O
defined O
by O
the O
presence O
of O
at O
least O
three O
of O
the O
following O
congenital O
malformations O
: O
vertebral O
defects O
, O
anal O
atresia O
, O
cardiac O
defects O
, O
tracheo O
- O
esophageal O
fistula O
, O
renal O
anomalies O
, O
and O
limb O
abnormalities O
. O
In O
addition O
to O
these O
core O
component O
features O
, O
patients O
may O
also O
have O
other O
congenital O
anomalies O
. O
Although O
diagnostic O
criteria O
vary O
, O
the O
incidence B-EPI
is O
estimated O
at O
approximately O
1 O
in O
10,000 O
to O
1 O
in O
40,000 O
live O
- O
born O
infants O
. O
The O
condition O
is O
ascertained O
clinically O
by O
the O
presence O
of O
the O
above O
- O
mentioned O
malformations O
; O
importantly O
, O
there O
should O
be O
no O
clinical O
or O
laboratory O
- O
based O
evidence O
for O
the O
presence O
of O
one O
of O
the O
many O
similar O
conditions O
, O
as O
the O
differential O
diagnosis O
is O
relatively O
large O
. O
This O
differential O
diagnosis O
includes O
( O
but O
is O
not O
limited O
to O
) O
Baller O
- O
Gerold O
syndrome O
, O
CHARGE O
syndrome O
, O
Currarino O
syndrome O
, O
deletion O
22q11.2 O
syndrome O
, O
Fanconi O
anemia O
, O
Feingold O
syndrome O
, O
Fryns O
syndrome O
, O
MURCS O
association O
, O
oculo O
- O
auriculo O
- O
vertebral O
syndrome O
, O
Opitz O
G O
/ O
BBB O
syndrome O
, O
Pallister O
- O
Hall O
syndrome O
, O
Townes O
- O
Brocks O
syndrome O
, O
and O
VACTERL O
with O
hydrocephalus O
. O
Though O
there O
are O
hints O
regarding O
causation O
, O
the O
aetiology O
has O
been O
identified O
only O
in O
a O
small O
fraction O
of O
patients O
to O
date O
, O
likely O
due O
to O
factors O
such O
as O
a O
high O
degree O
of O
clinical O
and O
causal O
heterogeneity O
, O
the O
largely O
sporadic O
nature O
of O
the O
disorder O
, O
and O
the O
presence O
of O
many O
similar O
conditions O
. O
New O
genetic O
research O
methods O
offer O
promise O
that O
the O
causes O
of O
VACTERL O
association O
will O
be O
better O
defined O
in O
the O
relatively O
near O
future O
. O
Antenatal O
diagnosis O
can O
be O
challenging O
, O
as O
certain O
component O
features O
can O
be O
difficult O
to O
ascertain O
prior O
to O
birth O
. O
The O
management O
of O
patients O
with O
VACTERL O
/ O
VATER O
association O
typically O
centers O
around O
surgical O
correction O
of O
the O
specific O
congenital O
anomalies O
( O
typically O
anal O
atresia O
, O
certain O
types O
of O
cardiac O
malformations O
, O
and/or O
tracheo O
- O
esophageal O
fistula O
) O
in O
the O
immediate O
postnatal O
period O
, O
followed O
by O
long O
- O
term O
medical O
management O
of O
sequelae O
of O
the O
congenital O
malformations O
. O
If O
optimal O
surgical O
correction O
is O
achievable O
, O
the O
prognosis O
can O
be O
relatively O
positive O
, O
though O
some O
patients O
will O
continue O
to O
be O
affected O
by O
their O
congenital O
malformations O
throughout O
life O
. O
Importantly O
, O
patients O
with O
VACTERL O
association O
do O
not O
tend O
to O
have O
neurocognitive O
impairment O
. O
MYO15A O
is O
the O
third O
most O
crucial O
gene O
in O
hereditary O
sensorineural O
hearing O
loss O
after O
GJB2 O
and O
SLC26A4 O
. O
In O
the O
present O
study O
, O
we O
reviewed O
the O
prevalence B-EPI
of O
MYO15A O
mutations O
in O
patients O
with O
autosomal O
recessive O
non O
- O
syndromic O
hearing O
loss O
( O
ARNSHL O
) O
. O
In O
this O
meta O
- O
analysis O
, O
we O
conducted O
a O
search O
of O
PubMed O
, O
Web O
of O
Science O
, O
Excerpta O
Medica O
Database O
, O
and O
Scopus O
, O
and O
identified O
the O
articles O
up O
to O
September O
2019 O
without O
any O
time O
limit O
. O
Two O
investigators O
independently O
selected O
the O
relevant O
papers O
and O
extracted O
the O
required O
information O
. O
A O
total O
of O
44 O
case O
- O
control O
and O
case O
series O
studies O
were O
considered O
, O
and O
4176 O
patients O
and O
3706 O
healthy O
individuals O
, O
as O
the O
control O
group O
, O
were O
included O
. O
The O
pooled O
frequency O
of O
MYO15A O
mutations O
between O
patients O
suffering O
from O
ARNSHL O
was O
calculated O
as O
6.2 O
% O
( O
95 O
% O
CI O
: O
4.9 O
- O
7.8 O
, O
P O
-value<0.001 O
) O
. O
There O
was O
heterogeneity O
between O
our O
studies O
( O
P O
-value<0.001 O
, O
I2=58.1 O
% O
) O
; O
therefore O
, O
the O
random O
- O
effects O
model O
was O
utilized O
for O
analysis O
. O
Given O
the O
results O
, O
in O
many O
countries O
, O
the O
MYO15A O
gene O
has O
a O
significant O
contribution O
to O
hearing O
loss O
. O
Moreover O
, O
in O
several O
regions O
, O
specific O
dominant O
mutations O
in O
this O
gene O
have O
been O
reported O
. O
Therefore O
, O
the O
ethnic O
background O
should O
be O
considered O
to O
investigate O
the O
mutations O
of O
the O
MYO15A O
gene O
. O
Encephalocele O
is O
a O
herniation O
of O
the O
brain O
( O
cranium O
bifidum O
, O
cephalocele O
, O
craniocele O
) O
, O
formed O
during O
embryonic O
development O
, O
because O
of O
the O
incomplete O
closure O
of O
Neural O
Tube O
. O
It O
is O
a O
rare O
skull O
defect O
, O
with O
the O
incidence B-EPI
of O
0.8 B-STAT
to I-STAT
5 I-STAT
per I-STAT
10,000 I-STAT
live I-STAT
births I-STAT
. O
The O
article O
presents O
the O
medical O
history O
of O
a O
four O
month O
old O
patient O
, O
with O
frontoethmoidal O
encephalocele O
and O
multiple O
skeletal O
anomalies O
, O
such O
as O
amniotic O
knots O
on O
limbs O
, O
foot O
deformity O
, O
sindactilia O
and O
cleft O
palate O
. O
Introduction O
Ehlers O
- O
Danlos O
syndrome O
( O
EDS O
) O
, O
specifically O
the O
hypermobility O
type O
( O
hEDS O
) O
, O
is O
associated O
with O
a O
variety O
of O
gastrointestinal O
( O
GI O
) O
conditions O
. O
This O
study O
aims O
to O
evaluate O
the O
prevalence B-EPI
of O
and O
factors O
associated O
with O
gut O
dysmotility O
in O
patients O
with O
hEDS O
. O
Methods O
This O
is O
a O
retrospective O
study O
of O
hEDS O
patients O
conducted O
at O
the O
Cleveland O
Clinic O
's O
Center O
for O
Personalized O
Genetic O
Healthcare O
between O
January O
2007 O
and O
December O
2017 O
. O
Demographics O
, O
GI O
motility O
testing O
, O
endoscopic O
, O
and O
imaging O
data O
were O
extracted O
from O
the O
patients O
' O
charts O
. O
Results O
A O
total O
of O
218 O
patients O
with O
hEDS O
were O
identified O
. O
Among O
them O
, O
136 B-STAT
( O
62.3 O
% O
) O
patients O
had O
at O
least O
one O
GI O
symptom O
at O
the O
time O
of O
EDS O
diagnosis O
. O
Motility O
testing O
was O
performed O
and O
reported O
in O
42 B-STAT
( O
19.2 O
% O
) O
patients O
. O
Out O
of O
them O
, O
five O
( O
11.9 O
% O
) O
had O
esophageal O
dysmotility O
, O
18 B-STAT
( O
42.8 O
% O
) O
had O
gastroparesis O
, O
five O
( O
11.9 O
% O
) O
had O
small O
bowel O
/ O
colon O
altered O
transit O
time O
, O
and O
four O
( O
9.5 O
% O
) O
had O
global O
dysmotility O
. O
In O
univariable O
analysis O
, O
patients O
with O
postural O
orthostatic O
tachycardia O
syndrome O
( O
POTS O
) O
[ O
odds O
ratio O
( O
OR O
): O
8.88 O
, O
95 O
% O
CI O
: O
3.69 O
- O
24.9 O
, O
p<0.0001 O
] O
, O
fibromyalgia O
( O
OR O
: O
4.43 O
, O
95 O
% O
CI O
: O
2.04 O
- O
10.1 O
, O
p=0.0002 O
) O
, O
history O
of O
irritable O
bowel O
syndrome O
( O
OR O
: O
5.01 O
, O
95 O
% O
CI O
: O
2.31 O
- O
11.2 O
, O
p<0.0001 O
) O
, O
and O
gastroesophageal O
reflux O
disease O
( O
OR O
: O
3.33 O
, O
95 O
% O
CI O
: O
1.55 O
- O
7.44 O
, O
p=0.002 O
) O
were O
more O
likely O
to O
be O
diagnosed O
with O
GI O
dysmotility O
. O
On O
multivariable O
analysis O
, O
only O
POTS O
( O
OR O
: O
5.74 O
, O
95 O
% O
CI O
: O
2.25 O
- O
16.7 O
, O
p=0.0005 O
) O
was O
significantly O
associated O
with O
an O
increased O
likelihood O
of O
GI O
dysmotility O
. O
Conclusions O
This O
study O
suggests O
that O
GI O
symptoms O
are O
relatively O
common O
among O
patients O
with O
hEDS O
. O
Of O
the O
patients O
tested O
for O
dysmotility O
, O
76.2 O
% O
were O
found O
to O
have O
some O
form O
of O
dysmotility O
. O
POTS O
was O
found O
to O
be O
an O
independent O
predictive O
factor O
for O
GI O
dysmotility O
. O
The O
incidence B-EPI
of O
neonatal O
varicella O
has O
decreased O
dramatically O
since O
the O
introduction O
of O
the O
varicella O
vaccination O
. O
Although O
the O
varicella O
zoster O
virus O
is O
often O
associated O
with O
a O
mild O
infection O
, O
it O
may O
cause O
severe O
morbidity O
and O
mortality O
, O
particularly O
in O
the O
neonatal O
period O
and O
immunocompromised O
hosts O
. O
We O
report O
a O
case O
of O
neonatal O
varicella O
acquired O
from O
maternal O
zoster O
in O
a O
mother O
on O
biological O
immunosuppressive O
therapy O
. O
Following O
the O
diagnosis O
, O
the O
baby O
improved O
on O
antiviral O
therapy O
without O
any O
neurological O
sequelae O
. O
This O
case O
highlights O
the O
limited O
published O
data O
on O
neonatal O
varicella O
following O
herpes O
zoster O
reactivation O
to O
inform O
practice O
. O
This O
includes O
the O
role O
of O
varicella O
zoster O
immunoglobulin O
in O
neonates O
exposed O
to O
maternal O
zoster O
, O
the O
degree O
of O
trans O
- O
placental O
immunity O
and O
optimum O
antiviral O
dosing O
and O
duration O
. O
In O
our O
previous O
studies O
, O
we O
discovered O
the O
congenital O
cold O
syndrome O
( O
CCS O
) O
, O
which O
is O
characterized O
by O
' O
qi O
deficiency O
and O
qi O
stagnation O
, O
mixed O
cold O
and O
heat O
. O
' O
And O
there O
is O
a O
type O
of O
syndrome O
with O
special O
incidence B-EPI
characteristic O
. O
However O
, O
the O
diagnosis O
of O
CCS O
still O
lacks O
an O
objective O
basis O
. O
In O
this O
study O
, O
we O
performed O
Tandem O
Mass O
Tag O
( O
TMT O
) O
based O
on O
quantitative O
proteomics O
technology O
to O
screen O
the O
significantly O
differentially O
expressed O
proteins O
( O
DEPs O
) O
in O
serum O
of O
patients O
with O
coronary O
heart O
disease O
( O
CHD O
) O
patients O
with O
CCS O
, O
patients O
with O
heart O
and O
kidney O
yang O
deficiency O
, O
and O
healthy O
people O
. O
A O
total O
of O
22 O
DEPs O
( O
nine O
upregulated O
and O
13 O
downregulated O
) O
were O
identified O
between O
patients O
with O
CCS O
and O
healthy O
subjects O
. O
Next O
, O
we O
performed O
GO O
and O
KEGG O
pathway O
enrichment O
analysis O
, O
we O
found O
the O
primary O
functions O
of O
DEPs O
of O
CCS O
were O
binding O
, O
catalytic O
activity O
, O
and O
molecular O
function O
regulator O
. O
These O
DEPs O
were O
mainly O
involved O
in O
important O
biological O
processes O
, O
such O
as O
cellular O
process O
, O
response O
to O
stimulus O
, O
localization O
, O
metabolic O
process O
, O
and O
biological O
regulation O
. O
The O
KEGG O
analysis O
revealed O
that O
the O
DEPs O
showed O
significant O
changes O
in O
fructose O
and O
mannose O
metabolism O
, O
Pentose O
phosphate O
pathway O
, O
and O
Arrhythmogenic O
right O
ventricular O
cardiomyopathy O
. O
After O
parallel O
reaction O
monitoring O
( O
PRM O
) O
verification O
, O
four O
upregulated O
target O
proteins O
( O
ALDOA O
, O
PCYOX1 O
, O
Crisp3 O
and O
IGLV4 O
- O
69 O
) O
and O
three O
downregulated O
proteins O
( O
ALDOC O
, O
ADAMTSL-2 O
and O
C3 O
) O
were O
accurately O
identified O
. O
These O
proteins O
were O
mainly O
related O
to O
immune O
response O
and O
glucose O
metabolism O
. O
These O
DEPs O
could O
be O
the O
marker O
proteins O
of O
coronary O
heart O
disease O
with O
CCS O
. O
This O
findings O
help O
to O
reveal O
the O
pathogenesis O
of O
CHD O
with O
CCS O
and O
provide O
potential O
therapeutic O
targets O
. O
Objective O
We O
recently O
recorded O
a O
high O
prevalence B-EPI
of O
inclusion O
body O
myositis O
( O
IBM O
) O
in O
patients O
with O
Sjögren O
's O
syndrome O
( O
SS O
) O
. O
Whether O
myositis O
patients O
with O
SS O
differ O
from O
myositis O
patients O
without O
SS O
in O
terms O
of O
the O
characteristics O
of O
the O
myositis O
is O
currently O
unknown O
. O
Anti O
- O
cytosolic O
5'-nucleotidase O
1 O
A O
( O
cN1A O
) O
has O
recently O
been O
proposed O
as O
a O
biomarker O
for O
IBM O
but O
is O
also O
frequent O
in O
SS B-LOC
. O
Whether O
anti O
- O
cN1A O
is O
independently O
associated O
with O
IBM O
is O
still O
an O
open O
question O
. O
We O
aimed O
to O
assess O
the O
significance O
of O
SS O
and O
anti O
- O
cN1A O
in O
myositis O
patients O
. O
Methods O
Cumulative O
data O
on O
all O
myositis O
patients O
( O
EULAR O
/ O
ACR O
2017 O
criteria O
) O
screened O
for O
SS O
( O
ACR O
/ O
EULAR O
2016 O
criteria O
) O
in O
a O
single O
center O
were O
analyzed O
. O
Ninety O
- O
nine O
patients O
were O
included O
, O
covering O
the O
whole O
spectrum O
of O
EULAR O
/ O
ACR O
2017 O
myositis O
subgroups O
and O
with O
a O
median O
follow O
- O
up O
of O
6 O
years O
[ O
range O
1.0 O
- O
37.5 O
] O
. O
The O
34 O
myositis O
patients O
with O
SS O
( O
myositis O
/ O
SS+ O
) O
were O
compared O
with O
the O
65 O
myositis O
patients O
without O
SS O
( O
myositis O
/ O
SS- O
) O
. O
Results O
IBM O
was O
present O
in O
24 O
% O
of O
the O
myositis O
/ O
SS+ O
patients O
vs O
6 O
% O
of O
the O
myositis O
/ O
SS- O
group O
( O
p O
= O
0.020 O
) O
. O
None O
of O
the O
IBM O
patients O
responded O
to O
treatment O
, O
whether O
they O
had O
SS O
or O
not O
. O
Anti O
- O
cN1A O
was O
more O
frequent O
in O
myositis O
/ O
SS+ O
patients O
( O
38 O
% O
vs O
6 O
% O
, O
p O
= O
0.0005 O
) O
, O
independently O
of O
the O
higher O
prevalence B-EPI
of O
IBM O
in O
this O
group O
( O
multivariate O
p O
- O
value O
: O
0.02 O
) O
. O
Anti O
- O
cN1A O
antibody O
specificity O
for O
IBM O
was O
0.96 O
[ O
95 O
% O
CI O
, O
0.87 O
- O
0.99 O
] O
in O
the O
myositis O
SS- O
group O
but O
dropped O
to O
0.70 O
[ O
95 O
% O
CI O
, O
0.48 O
- O
0.85 O
] O
in O
the O
myositis O
SS/+ O
group O
. O
Interpretation O
In O
myositis O
patients O
, O
SS O
is O
associated O
with O
IBM O
and O
with O
anti O
- O
cN1A O
antibodies O
, O
independently O
of O
the O
IBM O
diagnosis O
. O
As O
a O
consequence O
, O
anti O
- O
cN1A O
has O
limited O
specificity O
for O
IBM O
in O
myositis O
patients O
with O
SS O
. O
Background O
Target O
organ O
damage O
( O
mainly O
cardiac O
and O
renal O
damage O
) O
is O
easy O
to O
evaluate O
in O
outpatient O
clinics O
and O
offers O
valuable O
information O
about O
patient O
's O
cardiovascular O
risk O
. O
The O
purpose O
of O
this O
study O
was O
to O
evaluate O
, O
using O
simple O
methods O
, O
the O
prevalence B-EPI
of O
cardiac O
and O
renal O
damage O
and O
its O
relationship O
to O
the O
presence O
of O
established O
cardiovascular O
disease O
( O
CVD O
) O
, O
in O
patients O
with O
hypertension O
( O
HT O
) O
and O
type O
2 O
diabetes O
mellitus O
( O
DM O
) O
. O
Methods O
The O
RICARHD O
study O
is O
a O
multicentre O
, O
cross O
- O
sectional O
study O
made O
by O
293 O
investigators O
in O
Nephrology O
and O
Internal O
Medicine O
Spanish O
outpatient O
clinics O
, O
and O
included O
patients O
aged O
55 O
years O
or O
more O
with O
HT O
and O
type O
2 O
DM O
with O
more O
than O
six O
months O
of O
diagnosis O
. O
Demographic O
, O
clinical O
and O
biochemical O
data O
, O
and O
CVD O
were O
collected O
from O
the O
clinical O
records O
. O
Cardiac O
damage O
was O
defined O
by O
the O
presence O
of O
electrocardiographic O
left O
ventricular O
hypertrophy O
( O
ECG O
- O
LVH O
) O
, O
and O
renal O
damage O
by O
a O
calculated O
glomerular O
filtration O
rate O
( O
GFR O
) O
of O
< O
60 O
ml O
/ O
min/1.73 O
m2 O
, O
and/or O
the O
presence O
of O
an O
albumin O
/ O
creatinine O
ratio O
> O
or O
= O
30 O
mg O
/ O
g O
; O
or O
an O
urinary O
albumin O
excretion O
( O
UAE O
) O
> O
or O
= O
30 O
mg/24 O
hours O
. O
Results O
2339 O
patients O
( O
mean O
age O
68.9 O
years O
, O
48.2 O
% O
females O
, O
51.3 O
% O
with O
established O
CVD O
) O
were O
included O
. O
ECG O
- O
LVH O
was O
present O
in O
22.9 O
% O
of O
the O
sample O
, O
GFR O
< O
60 O
ml O
/ O
min/1.73 O
m2 O
in O
45.1 O
% O
, O
and O
abnormal O
UAE O
in O
58.7 B-STAT
% I-STAT
. O
Compared O
with O
the O
reference O
patients O
( O
those O
without O
neither O
cardiac O
nor O
renal O
damage O
) O
, O
patients O
with O
ECG O
- O
LVH O
alone O
( O
OR O
2.20 O
, O
[ O
95%CI O
1.43 O
- O
3.38 O
] O
) O
, O
or O
kidney O
damage O
alone O
( O
OR O
1.41 O
, O
[ O
1.13 O
- O
1.75 O
] O
) O
showed O
an O
increased O
prevalence B-EPI
of O
CVD O
. O
The O
presence O
of O
both O
ECG O
- O
LVH O
and O
renal O
damage O
was O
associated O
with O
the O
higher O
prevalence B-EPI
( O
OR O
3.12 O
, O
[ O
2.33 O
- O
4.19 O
] O
) O
. O
After O
stratifying O
by O
gender O
, O
this O
relationship O
was O
present O
for O
both O
, O
men O
and O
women O
. O
Conclusion O
In O
patients O
with O
HT O
and O
type O
2 O
DM O
, O
ECG O
- O
LVH O
or O
renal O
damage O
, O
evaluated O
using O
simple O
methods O
, O
are O
associated O
with O
an O
increased O
prevalence B-EPI
of O
established O
CVD O
. O
The O
simultaneous O
presence O
of O
both O
cardiac O
and O
renal O
damage O
was O
associated O
to O
the O
higher O
prevalence B-EPI
of O
CVD O
, O
affording O
complementary O
information O
. O
A O
systematic O
assessment O
of O
cardiac O
and O
renal O
damage O
complements O
the O
risk O
assessment O
of O
these O
patients O
with O
HT O
and O
type O
2 O
DM O
. O
Objectives O
This O
study O
aimed O
to O
report O
the O
prevalence B-EPI
and O
clinical O
characteristics O
of O
adults O
with O
cerebral O
palsy O
( O
CP O
) O
in O
a O
geographically O
defined O
region O
of O
the O
UK B-LOC
. O
Design O
and O
setting O
Cross O
- O
sectional O
study O
using O
the O
Northern O
Ireland O
Cerebral O
Palsy O
Register O
( O
NICPR O
) O
. O
Participants O
All O
validated O
cases O
known O
to O
the O
NICPR O
, O
born O
1981 O
- O
2001 O
and O
alive O
and O
resident O
in O
Northern B-LOC
Ireland I-LOC
at O
age O
19 O
years O
were O
included O
. O
Results O
The O
study O
included O
1218 O
persons O
with O
CP O
aged O
19 O
- O
39 O
years O
, O
46 O
of O
whom O
died O
in O
adulthood O
. O
The O
prevalence B-EPI
of O
CP O
was O
2.38 B-STAT
per I-STAT
1000 I-STAT
. O
The O
majority O
of O
cases O
had O
spastic O
CP O
( O
n=1132/1218 O
, O
93 O
% O
) O
and O
could O
walk O
( O
n=949/1218 O
, O
78 O
% O
) O
. O
Those O
that O
died O
in O
adulthood O
typically O
had O
bilateral O
spastic O
CP O
( O
n=39/46 O
) O
and O
used O
a O
wheelchair O
( O
n=40/46 O
) O
. O
Conclusion O
The O
prevalence B-EPI
of O
CP O
in O
adults O
is O
similar O
to O
other O
common O
neurological O
conditions O
such O
as O
multiple O
sclerosis O
and O
Parkinson O
's O
disease O
. O
The O
needs O
of O
adults O
with O
CP O
vary O
widely O
with O
almost O
half O
having O
two O
or O
more O
associated O
impairments O
that O
may O
require O
multiprofessional O
and O
multiagency O
coordination O
. O
Results O
from O
this O
study O
can O
be O
used O
to O
inform O
transformation O
of O
health O
and O
care O
services O
for O
adults O
with O
CP O
. O
Fanconi O
anemia O
( O
FA O
) O
is O
a O
recessive O
DNA O
instability O
disorder O
associated O
with O
developmental O
abnormalities O
, O
bone O
marrow O
failure O
, O
and O
a O
predisposition O
to O
cancer O
. O
Based O
on O
their O
sensitivity O
to O
DNA O
cross O
- O
linking O
agents O
, O
FA O
cells O
have O
been O
assigned O
to O
15 O
complementation O
groups O
, O
and O
the O
associated O
genes O
have O
been O
identified O
. O
Founder O
mutations O
have O
been O
found O
in O
different O
FA O
genes O
in O
several O
populations O
. O
The O
majority O
of O
Dutch O
FA O
patients O
belongs O
to O
complementation O
group O
FA O
- O
C. O
Here O
, O
we O
report O
15 O
patients O
of O
Dutch O
ancestry O
and O
a O
large O
Canadian O
Manitoba B-LOC
Mennonite O
kindred O
carrying O
the O
FANCC O
c.67delG O
mutation O
. O
Genealogical O
investigation O
into O
the O
ancestors O
of O
the O
Dutch O
patients O
shows O
that O
these O
ancestors O
lived O
in O
four O
distinct O
areas O
in O
The B-LOC
Netherlands I-LOC
. O
We O
also O
show O
that O
the O
Dutch O
and O
Manitoba B-LOC
Mennonite I-LOC
FANCC O
c.67delG O
patients O
share O
the O
same O
haplotype O
surrounding O
this O
mutation O
, O
indicating O
a O
common O
founder O
. O
Approximately O
one O
- O
third O
of O
the O
world O
's O
population O
is O
infected O
with O
Mycobacterium O
tuberculosis O
, O
and O
it O
is O
a O
leading O
cause O
of O
infertility O
in O
endemic O
countries O
. O
The O
global B-LOC
incidence B-EPI
of O
tuberculosis O
( O
TB O
) O
is O
growing O
at O
approximately B-STAT
0.4 I-STAT
% I-STAT
per O
year O
, O
and O
much O
faster O
in O
sub O
- O
Saharan O
Africa O
. O
TB O
causing O
fertility O
is O
rare O
in O
developed O
countries O
. O
We O
present O
a O
case O
of O
genital O
tuberculosis O
causing O
Asherman O
's O
syndrome O
and O
resultant O
infertility O
. O
The O
patient O
is O
a O
34 O
- O
year O
- O
old O
P0 O
who O
presented O
to O
care O
after O
a O
prolonged O
period O
of O
secondary O
amenorrhea O
and O
infertility O
. O
She O
underwent O
a O
hysterosalpingogram O
which O
demonstrated O
no O
free O
spill O
and O
a O
diagnostic O
hysteroscopy O
which O
had O
findings O
of O
mottled O
endometrium O
. O
Pathology O
returned O
positive O
for O
Mycobacterium O
tuberculosis O
. O
The O
patient O
was O
treated O
with O
9 O
months O
of O
antituberculous O
therapy O
. O
While O
she O
has O
not O
yet O
succeeded O
in O
becoming O
pregnant O
, O
the O
patient O
has O
started O
to O
notice O
cyclic O
spotting O
, O
indicating O
possible O
return O
of O
menses O
. O
This O
case O
highlights O
the O
importance O
of O
TB O
treatment O
and O
considering O
TB O
in O
patients O
who O
present O
with O
unexplained O
infertility O
. O
Recent O
expansion O
of O
arboviruses O
such O
as O
West B-LOC
Nile I-LOC
( O
WNV O
) O
, O
Usutu O
( O
USUV O
) O
, O
and O
tick O
- O
borne O
encephalitis O
( O
TBEV O
) O
over O
their O
natural O
range O
of O
distribution O
needs O
strengthening O
their O
surveillance O
. O
As O
common O
viral O
vertebrate O
hosts O
, O
birds O
and O
horses O
deserve O
special O
attention O
with O
routine O
serological O
surveillance O
. O
Here O
, O
we O
estimated O
the O
seroprevalence O
of O
WNV O
, O
USUV O
and O
TBEV O
in O
160 O
migrating O
/ O
resident O
birds O
and O
60 O
horses O
sampled O
in O
Mazandaran B-LOC
, O
Golestan B-LOC
, O
North B-LOC
Khorasan I-LOC
, O
Kordestan B-LOC
provinces O
and O
Golestan B-LOC
province I-LOC
of O
Iran B-LOC
respectively O
. O
ELISA O
results O
showed O
that O
of O
220 O
collected O
samples O
, O
32 O
samples O
( O
14.54 O
% O
) O
, O
including O
22 O
birds O
and O
10 O
horses O
, O
were O
positive O
. O
Microsphere O
immunoassay O
results O
showed O
that O
16.7 O
% O
( O
10/60 O
) O
of O
horse O
blood O
samples O
collected O
in O
Golestan B-LOC
province I-LOC
were O
seropositive O
against O
WNV O
( O
7 B-STAT
; O
11.7 O
% O
) O
, O
Flavivirus O
( O
2 B-STAT
; O
3.3 O
% O
) O
and O
seropositive O
for O
USUV O
or O
WNV O
( O
1 B-STAT
; O
1.7 O
% O
) O
. O
Furthermore O
, O
micro O
virus O
neutralization O
tests O
revealed O
that O
four O
of O
seven O
ELISA O
- O
positive O
bird O
blood O
samples O
were O
seropositive O
against O
WNV O
: O
two O
Egyptian O
vultures O
, O
and O
one O
long O
- O
legged O
buzzard O
collected O
in O
Golestan O
province O
as O
well O
as O
a O
golden O
eagle O
collected O
in O
North B-LOC
Khorasan I-LOC
province O
. O
No O
evidence O
of O
seropositivity O
with O
TBEV O
was O
observed O
in O
collected O
samples O
. O
We O
showed O
that O
WNV O
, O
responsible O
for O
neuroinvasive O
infection O
in O
vertebrates O
, O
is O
circulating O
among O
birds O
and O
horses O
in O
Iran B-LOC
, O
recommending O
a O
sustained O
surveillance O
of O
viral O
infections O
in O
animals O
, O
and O
anticipating O
future O
infections O
in O
humans O
. O
Past O
studies O
strongly O
connected O
stool O
consistency O
- O
as O
measured O
by O
Bristol O
Stool O
Scale O
( O
BSS)-with O
microbial O
gene O
richness O
and O
intestinal O
inflammation O
, O
colonic O
transit O
time O
and O
metabolome O
characteristics O
that O
are O
of O
clinical O
relevance O
in O
numerous O
gastro O
intestinal O
conditions O
. O
While O
retention O
time O
, O
defecation O
rate O
, O
BSS O
but O
not O
water O
activity O
have O
been O
shown O
to O
account O
for O
BSS O
- O
associated O
inflammatory O
effects O
, O
the O
potential O
correlation O
with O
the O
strength O
of O
a O
gel O
in O
the O
context O
of O
intestinal O
forces O
, O
abrasion O
, O
mucus O
imprinting O
, O
fecal O
pore O
clogging O
remains O
unexplored O
as O
a O
shaping O
factor O
for O
intestinal O
inflammation O
and O
has O
yet O
to O
be O
determined O
. O
Our O
study O
introduced O
a O
minimal O
pressure O
approach O
( O
MP O
) O
by O
probe O
indentation O
as O
measure O
of O
stool O
material O
crosslinking O
in O
fecal O
samples O
. O
Results O
reported O
here O
were O
obtained O
from O
170 O
samples O
collected O
in O
two O
independent O
projects O
, O
including O
males O
and O
females O
, O
covering O
a O
wide O
span O
of O
moisture O
contents O
and O
BSS O
. O
MP O
values O
increased O
exponentially O
with O
increasing O
consistency O
( O
i.e. O
, O
lower O
BSS O
) O
and O
enabled O
stratification O
of O
samples O
exhibiting O
mixed O
BSS O
classes O
. O
A O
trade O
- O
off O
between O
lowest O
MP O
and O
highest O
dry O
matter O
content O
delineated O
the O
span O
of O
intermediate O
healthy O
density O
of O
gel O
crosslinks O
. O
The O
crossectional O
transects O
identified O
fecal O
surface O
layers O
with O
exceptionally O
high O
MP O
and O
of O
< O
5 O
mm O
thickness O
followed O
by O
internal O
structures O
with O
an O
order O
of O
magnitude O
lower O
MP O
, O
characteristic O
of O
healthy O
stool O
consistency O
. O
The O
MP O
and O
BSS O
values O
reported O
in O
this O
study O
were O
coupled O
to O
reanalysis O
of O
the O
PlanHab O
data O
and O
fecal O
1H O
- O
NMR O
metabolomes O
reported O
before O
. O
The O
exponential O
association O
between O
stool O
consistency O
and O
MP O
determined O
in O
this O
study O
was O
mirrored O
in O
the O
elevated O
intestinal O
and O
also O
systemic O
inflammation O
and O
other O
detrimental O
physiological O
deconditioning O
effects O
observed O
in O
the O
PlanHab O
participants O
reported O
before O
. O
The O
MP O
approach O
described O
in O
this O
study O
can O
be O
used O
to O
better O
understand O
fecal O
hardness O
and O
its O
relationships O
to O
human O
health O
as O
it O
provides O
a O
simple O
, O
fine O
scale O
and O
objective O
stool O
classification O
approach O
for O
the O
characterization O
of O
the O
exact O
sampling O
locations O
in O
future O
microbiome O
and O
metabolome O
studies O
. O
OBJECTIVES O
: O
The O
incidence B-EPI
of O
neonatal O
herpes O
simplex O
virus O
( O
nHSV O
) O
infections O
is O
monitored O
periodically O
in O
the O
Netherlands B-LOC
, O
yet O
management O
and O
outcome O
is O
unknown O
. O
Comprehensive O
national O
guidelines O
are O
lacking O
. O
We O
aim O
to O
describe O
management O
and O
outcome O
in O
the O
last O
decade O
to O
explore O
current O
diagnostic O
and O
therapeutic O
challenges O
. O
We O
aim O
to O
identify O
possible O
variability O
in O
management O
of O
patients O
with O
a O
suspected O
nHSV O
infection O
. O
METHODS O
: O
We O
conducted O
a O
retrospective O
case O
series O
of O
management O
and O
outcome O
of O
nHSV O
infections O
at O
2 O
tertiary O
care O
center O
locations O
in O
the O
Netherlands B-LOC
. O
RESULTS O
: O
An O
nHSV O
infection O
was O
diagnosed O
in O
1 O
% O
( O
12 O
of O
1348 O
) O
of O
patients O
in O
whom O
polymerase O
chain O
reaction O
for O
HSV O
was O
performed O
. O
Of O
the O
patients O
with O
nHSV O
infection O
, O
3 O
of O
12 O
died O
, O
and O
4 O
of O
9 B-STAT
( O
44 O
% O
) O
survivors O
suffered O
neurologic O
sequelae O
. O
Neurologic O
symptoms O
at O
presentation O
were O
seen O
in O
only O
2 O
of O
8 O
patients O
with O
nHSV O
encephalitis O
. O
A O
cerebral O
spinal O
fluid O
analysis O
was O
performed O
in O
3 O
of O
6 O
patients O
presenting O
with O
skin O
lesions O
. O
Only O
3 O
of O
6 O
patients O
with O
neurologic O
symptoms O
received O
suppressive O
therapy O
. O
nHSV O
infection O
was O
diagnosed O
in O
8 O
of O
189 B-STAT
( O
4 O
% O
) O
patients O
who O
were O
empirically O
treated O
. O
CONCLUSIONS O
: O
Management O
of O
nHSV O
infection O
, O
particularly O
when O
presented O
with O
skin O
lesions O
, O
is O
inconsistent O
. O
Many O
infants O
without O
a O
HSV O
infection O
are O
exposed O
to O
antiviral O
medication O
. O
There O
is O
substantial O
interhospital O
variation O
in O
diagnostic O
and O
therapeutic O
management O
of O
a O
suspected O
infection O
. O
Comprehensive O
guidelines O
need O
to O
be O
developed O
to O
standardize O
management O
of O
suspected O
nHSV O
infection O
. O
Purpose O
of O
review O
The O
global B-LOC
prevalence B-EPI
of O
obesity O
has O
increased O
rapidly O
over O
the O
last O
decades O
, O
posing O
a O
severe O
threat O
to O
human O
health O
. O
Currently O
, O
bariatric O
surgery O
is O
the O
most O
effective O
therapy O
for O
patients O
with O
morbid O
obesity O
. O
It O
is O
unknown O
whether O
this O
treatment O
is O
also O
suitable O
for O
patients O
with O
obesity O
due O
to O
a O
confirmed O
genetic O
defect O
( O
genetic O
obesity O
disorders O
) O
. O
Therefore O
, O
this O
review O
aims O
to O
elucidate O
the O
role O
of O
bariatric O
surgery O
in O
the O
treatment O
of O
genetic O
obesity O
. O
Recent O
findings O
In O
monogenic O
non O
- O
syndromic O
obesity O
, O
an O
underlying O
genetic O
defect O
seems O
to O
be O
the O
most O
important O
factor O
determining O
the O
efficacy O
of O
bariatric O
surgery O
. O
In O
syndromic O
obesity O
, O
bariatric O
surgery O
result O
data O
are O
scarce O
, O
and O
even O
though O
some O
promising O
follow O
- O
up O
results O
have O
been O
reported O
, O
caution O
is O
required O
as O
patients O
with O
more O
severe O
behavioral O
and O
developmental O
disorders O
might O
have O
poorer O
outcomes O
. O
There O
is O
limited O
evidence O
in O
support O
of O
bariatric O
surgery O
as O
a O
treatment O
option O
for O
genetic O
obesity O
disorders O
; O
hence O
, O
no O
strong O
statements O
can O
be O
made O
regarding O
the O
efficacy O
and O
safety O
of O
these O
procedures O
for O
these O
patients O
. O
However O
, O
considering O
that O
patients O
with O
genetic O
obesity O
often O
present O
with O
life O
- O
threatening O
obesity O
- O
related O
comorbidities O
, O
we O
believe O
that O
bariatric O
surgery O
could O
be O
considered O
a O
last O
- O
resort O
treatment O
option O
in O
selected O
patients O
. O
The O
treatment O
of O
Graves O
' O
disease O
is O
based O
on O
three O
therapies O
: O
medical O
treatment O
with O
synthetic O
antithyroid O
agents O
, O
surgery O
and O
radioactive O
- O
iodine O
therapy O
. O
The O
purpose O
of O
our O
study O
was O
to O
study O
the O
role O
and O
effectiveness O
of O
radioactive O
- O
iodine O
therapy O
for O
the O
treatment O
of O
Graves O
' O
disease O
. O
We O
conducted O
a O
retrospective O
, O
descriptive O
study O
of O
the O
epidemiological O
, O
clinical O
, O
paralclinical O
and O
therapeutic O
features O
of O
54 O
patients O
with O
Graves O
' O
disease O
managed O
and O
treated O
with O
iodine-131 O
as O
well O
as O
of O
their O
short- O
and O
medium O
- O
term O
remission O
rate O
. O
The O
sex O
ratio O
was O
0.45 O
. O
The O
average O
age O
of O
patients O
was O
38,33 O
± O
12.7 O
years O
. O
The O
most O
common O
functional O
signs O
were O
weight O
loss O
, O
tremors O
and O
palpitations O
. O
Mean O
FT4 O
was O
54,51 O
± O
19,56 O
ng O
/ O
dl O
( O
ranging O
from O
8,90 O
and O
100 O
) O
. O
Mean O
TSHus O
was O
0,074 O
± O
0,29 O
µIU O
/ O
ml O
. O
Synthetic O
antithyroid O
drugs O
were O
used O
in O
49 O
patients O
; O
83,67 O
% O
of O
cases O
had O
persistent O
hyperthyroidism O
. O
Radioactive O
- O
iodine O
therapy O
was O
used O
as O
first O
- O
line O
therapy O
in O
9,3 O
% O
of O
cases O
and O
as O
second O
- O
line O
therapy O
in O
90,7 O
% O
of O
cases O
. O
Mean O
activity O
was O
13,29 O
mCi O
± O
1,46 O
ranging O
from O
10 O
to O
15 O
mCi O
. O
The O
first O
assessment O
of O
hormonal O
status O
was O
performed O
after O
an O
average O
post O
- O
treatment O
period O
of O
1,91 O
months O
; O
29 O
patients O
( O
53,7 O
% O
) O
achieved O
remission O
( O
eu- O
or O
hypo O
- O
thyroidism O
) O
. O
After O
a O
12 O
month O
- O
follow O
- O
up O
, O
patients O
' O
course O
was O
marked O
by O
remission O
in O
88,88 O
% O
of O
cases O
( O
euthyroidism O
in O
14,8 O
% O
and O
hypothyroidism O
in O
74 O
% O
of O
cases O
) O
. O
Radioactive O
- O
iodine O
therapy O
is O
an O
effective O
treatment O
for O
Graves O
' O
disease O
. O
High O
radioactive O
iodine O
dose O
provides O
high O
remission O
rate O
. O
Over O
the O
last O
10 O
years O
, O
evidence O
has O
accumulated O
that O
autoimmune O
Addison O
's O
disease O
( O
AAD O
) O
is O
a O
heterogeneous O
disease O
. O
Residual O
adrenal O
function O
, O
characterised O
by O
persistent O
secretion O
of O
cortisol O
, O
other O
glucocorticoids O
and O
mineralocorticoids O
is O
present O
in O
around O
30 O
% O
of O
patients O
with O
established O
AAD O
, O
and O
appears O
commoner O
in O
men O
. O
This O
persistent O
steroidogenesis O
is O
present O
in O
some O
patients O
with O
AAD O
for O
more O
than O
20 O
years O
, O
but O
it O
is O
commoner O
in O
people O
with O
shorter O
disease O
duration O
. O
The O
clinical O
significance O
of O
residual O
adrenal O
function O
is O
not O
fully O
clear O
at O
the O
moment O
, O
but O
as O
it O
signifies O
an O
intact O
adrenocortical O
stem O
cell O
population O
, O
it O
opens O
up O
the O
possibility O
of O
regeneration O
of O
adrenal O
steroidogenesis O
and O
improvement O
in O
adrenal O
failure O
for O
some O
patients O
. O
The O
global O
pandemic O
of O
COVID-19 O
has O
been O
lasting O
for O
more O
than O
one O
year O
and O
there O
is O
little O
known O
about O
the O
long O
- O
term O
health O
effects O
of O
the O
disease O
. O
Long O
- O
COVID O
is O
a O
new O
term O
that O
is O
used O
to O
describe O
the O
enduring O
symptoms O
of O
COVID-19 O
survivors O
. O
Huang O
et O
al O
. O
reported O
that O
fatigue O
, O
muscle O
weakness O
, O
sleep O
disturbances O
, O
anxiety O
, O
and O
depression O
were O
the O
most O
common O
complaints O
in O
COVID-19 O
survivors O
after O
6 O
months O
of O
the O
infection O
. O
A O
recent O
meta O
- O
analysis O
showed O
that O
80 O
% O
of O
COVID-19 O
survivors O
have O
developed O
at O
least O
one O
long O
- O
term O
symptom O
and O
the O
most O
common O
five O
were O
fatigue O
, O
headache O
, O
attention O
deficit O
disorder O
, O
hair O
loss O
, O
and O
dyspnea O
. O
In O
this O
paper O
, O
we O
discuss O
the O
hypothesis O
that O
altered O
tryptophan O
absorption O
and O
metabolism O
could O
be O
the O
main O
contributor O
to O
the O
long O
- O
term O
symptoms O
in O
COVID-19 O
survivors O
. O
Background O
A O
higher O
risk O
of O
developing O
dementia O
is O
observed O
in O
patients O
with O
atrial O
fibrillation O
( O
AF O
) O
. O
Results O
are O
inconsistent O
regarding O
the O
risk O
of O
dementia O
when O
patients O
with O
AF O
use O
different O
anticoagulants O
. O
We O
aimed O
to O
investigate O
the O
risk O
of O
dementia O
in O
patients O
with O
AF O
receiving O
non O
- O
vitamin O
K O
antagonist O
oral O
anticoagulants O
( O
NOACs O
) O
compared O
with O
those O
receiving O
warfarin O
. O
Methods O
and O
Results O
We O
conducted O
a O
nationwide O
population O
- O
based O
cohort O
study O
of O
incident O
cases O
using O
the O
Taiwan O
National O
Health O
Insurance O
Research O
Database O
. O
We O
initially O
enlisted O
all O
incident O
cases O
of O
AF O
and O
then O
selected O
those O
treated O
with O
either O
NOACs O
or O
warfarin O
for O
at O
least O
90 O
days O
between O
2012 O
and O
2016 O
. O
First O
- O
ever O
diagnosis O
of O
dementia O
was O
the O
primary O
outcome O
. O
We O
performed O
propensity O
score O
matching O
to O
minimize O
the O
difference O
between O
each O
cohort O
. O
We O
used O
the O
Fine O
and O
Gray O
competing O
risk O
regression O
model O
to O
calculate O
the O
hazard O
ratio O
( O
HR O
) O
for O
dementia O
. O
We O
recruited O
12 O
068 O
patients O
with O
AF O
( O
6034 O
patients O
in O
each O
cohort O
) O
. O
The O
mean O
follow O
- O
up O
time O
was O
3.27 O
and O
3.08 O
years O
in O
the O
groups O
using O
NOACs O
and O
warfarin O
, O
respectively O
. O
Compared O
with O
the O
HR O
for O
the O
group O
using O
warfarin O
, O
the O
HR O
for O
dementia O
was O
0.82 O
( O
95 O
% O
CI O
, O
0.73 O
- O
0.92 O
; O
P O
= O
0.0004 O
) O
in O
the O
group O
using O
NOACs O
. O
Subgroup O
analysis O
demonstrated O
that O
users O
of O
NOAC O
aged O
65 O
to O
74 O
years O
, O
with O
a O
high O
risk O
of O
stroke O
or O
bleeding O
were O
associated O
with O
a O
lower O
risk O
of O
dementia O
than O
users O
of O
warfarin O
with O
similar O
characteristics O
. O
Conclusions O
Patients O
with O
AF O
using O
NOACs O
were O
associated O
with O
a O
lower O
risk O
of O
dementia O
than O
those O
using O
warfarin O
. O
Further O
randomized O
clinical O
trials O
are O
greatly O
needed O
to O
prove O
these O
findings O
. O