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Effects of bathing immediately after birth on early neonatal adaptation and morbidity: a prospective randomized comparative study. Because the risks and benefits of early bathing of newborn infants are not well established, we investigated the effects of bathing immediately after birth on rectal temperature, respiratory rate, heart rate, blood pressure, percutaneous arterial blood oxygen saturation (SpO2) and early neonatal morbidity. The study was designed as a randomized prospective comparative study in the neonatal care unit of a university hospital. A total of 187 healthy term and near-term newborn infants, who were delivered vaginally without asphyxia, between January and December 1997 were the study subjects. We compared findings in newborns who were bathed 2-5 min after birth (n = 95) with those of a control group (n = 92) who received dry care instead. Groups were comparable with respect to gestational age, birthweight, male: female ratio, Apgar score and umbilical blood pH. Rectal temperature was measured with an electronic thermometer immediately before the intervention bathing or dry care and at 30 min and 1, 2, 3, 8 and 12 h after birth. Heart rate, respiratory rate, systolic and diastolic blood pressure and SpO2 were measured at 1, 2, 8 and 12 h after birth. The incidence of early neonatal morbidity, including hyperbilirubinemia and gastrointestinal and respiratory problems, was also compared. Rectal temperature changed over time postnatally in both groups (P < 0.0001, ANOVA) and there was a significant difference in rectal temperature between groups (P< 0.0001, ANOVA). Mean (+/- SEM) rectal temperature at 30 min after birth (i.e. approximately within 20 min after intervention) was significantly higher in the bathed group than in the control (dry care) group (37.30 +/- 0.06 is 37.00 +/- 0.05 degrees C, respectively; P = 0.000022). Respiratory rate, heart rate, blood pressure and the ratio of the number of infants with SpO2 90-94% and 95-100% did not differ significantly between the two groups. The incidence of early neonatal morbidity, including vomiting, acute gastric mucosal lesion, polycythemia, need for tube feeding, phototherapy and oxygen therapy, also did not differ between the two groups. Early bathing, minutes after birth, did not appear to adversely affect the adaptation of healthy full-term and near-term newborn infants.

Phylogenetic relationships of unclassified, satellitic Pasteurellaceae obtained from different species of birds as demonstrated by 16S rRNA gene sequence comparison. Avian haemophili demonstrating in vitro satellitic growth, also referred to as the V-factor or NAD requirement, have mainly been classified with Avibacterium paragallinarum (Haemophilus paragallinarum), Avibacterium avium (Pasteurella avium), Avibacterium volantium (Pasteurella volantium) and Avibacterium sp. A (Pasteurella species A). The aim of the present study was to assess the taxonomic position of 18 V-factor-requiring isolates of unclassified Haemophilus-like organisms isolated from galliforme, anseriforme, columbiforme and gruiforme birds as well as kestrels and psittacine birds including budgerigars by conventional phenotypic tests and 16S rRNA gene sequencing. All isolates shared phenotypical characteristics which allowed classification with Pasteurellaceae. Haemolysis of bovine red blood cells was negative. Haemin (X-factor) was not required for growth. Maximum-likelihood phylogenetic analysis including bootstrap analysis showed that six isolates were related to the avian 16S rRNA group and were classified as Avibacterium according to 16S rRNA sequence analysis. Surprisingly, the other 12 isolates were unrelated to Avibacterium. Two isolates were unrelated to any of the known 16S rRNA groups of Pasteurellaceae. Two isolates were related to Volucribacter of the avian 16S rRNA group. Seven isolates belonged to the Testudinis 16S rRNA group and out of these, two isolates were closely related to taxa 14 and 32 of Bisgaard, whereas four other isolates were found to form a genus-like group distantly related to taxon 40 and one isolate remained distantly related to other members of the Testudinis group. One isolate was closely related to taxon 26 (a member of Actinobacillus sensu stricto). The study documented major genetic diversity among V-factor-requiring avian isolates beyond the traditional interpretation that they only belong to Avibacterium, underlining the limited value of satellitic growth for identification of avian members of Pasteurellaceae. Our study also emphasized that these organisms will never be isolated without the use of special media satisfying the V-factor requirement.

The sympathetic neural apparatus of the rat uterus during the sexual cycle. A microspectral fluorescence-histochemical method was used to study the sympathetic neural apparatus of the rat uterus at different phases of the sexual cycle. Most nerve fibers, as perivascular plexuses and terminals emanating from them, were located in the myometrium. It is suggested that the uterus contains reserve ("silent" nerve fibers, which explains the variability in their appearance in this organ. Microspectrofluorimetric studies identified catecholamines and serotonin in varicose swellings and intervaricosity segments of nerve fibers; levels at test points showed a strong linear correlation at all stages of the sexual cycle. The greatest bioamine levels in most structural elements of the sympathetic neural apparatus of the uterus were seen in late diestrus. Early and late estrus and proestrus were characterized by low monoamine levels in adrenergic fibers. A number of significant differences were seen between the level of saturation with bioamines and the spatial distribution density of nerve fibers in the body and cervix of the uterus.

In-vivo immunofluorescent imaging in cases of posterior uveitis. In-vitro immunofluorescent assays/imaging are routinely used methods of detecting antigens. The ability to perform ocular angiography to study the choroidal and retinal vasculature in real time provides us with a unique opportunity to perform real time in-vivo immunofluorescent imaging. This unique combination of in-vivo immunofluorescent imaging and live imaging of choroidal and retinal circulation can help detect antigens of infective organisms in-vivo to diagnose causative infective aetiology in cases of choroiditis/retinitis. The following paper describes the basic designing of such an imaging platform.

[Proinflammatory cytokine stimulated NF-kappa B activation and the effect of dexamethasone in the human airway epithelial cells]. To observe the expression of NF-kappa B activation and the effect of dexamethasone on the NF-kappa B activity in the human airway epithelial cell line 16HBE after TNF-alpha stimulation. After 16HBE was treated with different concentration of TNF-alpha(10 U/ml, 100 U/ml, 1,000 U/ml) and dexamethasone (100 nmol/L), total RNA and cellular, nuclear protein were extracted at 1 hour, 2 hour, 4 hour, respectively. RT-PCR and electrophoresis mobility shift assay(EMSA) were used to detect the expression of IL-8 mRNA and NF-kappa B activation. The activity of NF-kappa B activation became stronger at 1 hour in the TNF-alpha stimulated group than the control, peaked at 2 hours and then decreased at 4 hours. Supershift assay confirmed that both p50 and p65 were components of active NF-kappa B. At the same time, IL-8 mRNA expression was elevated at 4 hours. After dexamethasone treatment, the expression of NF-kappa B activation and IL-8 mRNA became lower. It is suggested that activated NF-kappa B played a key role in the inflammatory process of respiratory diseases through regulating the expression of some important factors (cytokines). Glucocorticoid inhibited the activation of NF-kappa B and showed antiinflammatory effect.

Hidden covariation detection: a fundamental and ubiquitous phenomenon. H. Hendrickx, J. De Houwer, F. Baeyens, P. Eelen, and E. Van Avermaet (1997) reported a series of (mostly unsuccessful) studies on nonconscious hidden covariation detection (HCD); for example, they reported that out of 3 attempts to replicate P. Lewicki et al.'s studies, only 1 produced the expected results. They concluded that HCD may be not as general and robust as the previous research suggested, and they considered boundary conditions. In this article, the authors discuss a number of weaknesses of H. Hendrickx et al.'s experiments (and systematic deviations from the original methodology) that are potentially responsible for the lack of the expected results and discuss missing facts in their arguments (e.g., they failed to mention any published replications of the HCD studies from other than the present authors' laboratories). It is argued that when all evidence is considered, the proper conclusion is that nonconscious processing of covariations is not only general and robust but also a ubiquitous phenomenon mediating a variety of processes of acquisition of information.

Wriggly, squiffy, lummox, and boobs: What makes some words funny? Theories of humor tend to be post hoc descriptions, suffering from insufficient operationalization and a subsequent inability to make predictions about what will be found humorous and to what extent. Here we build on the Engelthaler & Hills' (2017) humor rating norms for 4,997 words, by analyzing the semantic, phonological, orthographic, and frequency factors that play a role in the judgments. We were able to predict the original humor rating norms and ratings for previously unrated words with greater reliability than the split half reliability in the original norms, as estimated from splitting those norms along gender or age lines. Our findings are consistent with several theories of humor, while suggesting that those theories are too narrow. In particular, they are consistent with incongruity theory, which suggests that experienced humor is proportional to the degree to which expectations are violated. We demonstrate that words are judged funnier if they are less common and have an improbable orthographic or phonological structure. We also describe and quantify the semantic attributes of words that are judged funny and show that they are partly compatible with the superiority theory of humor, which focuses on humor as scorn. Several other specific semantic attributes are also associated with humor. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Joint position sense in simulated changed-gravity environments. The proprioceptive position sense was investigated in an elbow-angle matching task in which the right forearm was moved passively by an experimenter and the left forearm actively by the subject. The right forearm could be immersed in water or loaded with a weight, to simulate micro- and hypergravity. We found that in simulated microgravity, matching performance was more variable than in normal gravity, and the right forearm deviated systematically upwards. The latter finding was limited to near-horizontal forearm positions (i.e., where the anticipated effects of gravity are strongest), and could be "reset" by intermittent visual feedback. The observed impairments of the proprioceptive position sense may adversely affect the manual performance of astronauts. In simulated hypergravity, we found no changes of variability and no systematic deviations. This outcome confirms our previous results that weight compensation is efficient even when only static (i.e., gravitational) cues are available.

P cell stimulating factor and glucocorticoids oppose the action of interferon-gamma in inducing Ia antigens on T-dependent mast cells (P cells). The expression of Ia antigens of cultured lines of T-dependent mast cells (TDMC) or persisting (P) cells was modulated by three hormones: interferon-gamma (IFN-gamma), P cell-stimulating factor (PSF), and glucocorticoids. The induction of Ia antigens by cloned IFN-gamma was inhibited by a homogeneous preparation of PSF, the T cell-derived factor that TDMC require for their in vitro growth. This inhibitory effect of PSF was dose-dependent and could not be overcome by increasing the levels of IFN-gamma. Other cytokines such as granulocyte/macrophage colony-stimulating factor, T cell growth factor, and L cell-derived macrophage colony-stimulating factor had no inhibitory effect. Thus, two different T cell lymphokines, PSF and IFN-gamma, have opposing effects on the expression of Ia antigens on TDMC. Glucocorticoids (hydrocortisone, corticosterone, dexamethasone, prednisolone, and fludrocortisone) antagonized the induction of Ia antigens by IFN-gamma, whereas sex steroids (progesterone, estradiol, and testosterone) and a mineralocorticoid (aldosterone) did not. The inhibitory effect of glucocorticoids could not be overcome by increasing concentrations of IFN-gamma, but was significantly inhibited by progesterone (10(-6) M), indicating the likely involvement of typical glucocorticoid receptors. In contrast to their effectiveness on macrophages, prostaglandin E2 and dibutyryl cyclic AMP only slightly inhibited the induction of Ia antigens on TDMC by IFN-gamma, whereas endotoxin (1 to 60 micrograms/ml) had no effect.

A study of salivary opiorphin levels using different anesthetic drugs and techniques - A randomized controlled clinical study. This study aimed at assessing the change in salivary opiorphin levels before and after administration of local anesthesia, with the use of three different local anesthetic agents, and different anaesthetic techniques. The investigators implemented a randomized controlled clinical study in 144 patients who required tooth extraction after administration of local anaesthesia. A total of 288 samples were collected in sterile containers before and after administration of local anesthetics. The salivary samples were centrifuged and salivary opiorphin levels were estimated using ELISA testing and spectrophotometric analysis. Statistical analysis was done using one way ANOVA and unpaired t test. There was a mean decrease in salivary opiorphin levels after administration of local anesthesia. There was no significant difference in the change in salivary opiorphin levels across different anesthetic techniques and different drug subgroups. The present study did not show much association between various local anesthetic agents and techniques and change in salivary opiorphin levels. The role of opiorphin as a biomarker for pain control and its effect on various pain control methods including local anesthesia must be evaluated in detail. Institutional review board number SRMDC/IRB/2014/MDS/No. 405.

[Cochlear implants]. Since the middle of 1984, the HNO-Klinik der Medizinischen Hochschule Hannover has provided deaf adults with a 22-channel cochlear implant (CI) device of Clark-NUCLEUS. The digital working system consists of an implantable stimulator/receiver and an externally worn speech processor. Energy and signals are transmitted transcutaneously via a transmitter coil. During the prevailing 26 operations (April 1986) the electrode array could be inserted at least 17 mm into the cochlea. The threshold and comfort levels of all patients were adjusted very quickly; the dynamic range usually grows during the first postoperative weeks. The individual rehabilitation results vary greatly, but all patients show a significant increase of vowel and consonant comprehension while using the speech processor and an improvement of words understood per minute in speech tracking from lip-reading alone to lip-reading with speech processor. Four months after surgery seven of 17 patients (group I) are able to understand on average 42.7 words per minute by speech tracking without lip-reading. Six patients (group II) recognise 69.2% of vowels and 42.5% of consonants by speech processor alone. Four patients (group III) can correctly repeat only vowels (52.3%) without lip-reading, but using the speech processor together with lip reading they have an improvement in consonant understanding of 37.9% and under freefield conditions they are able to understand up to 17.8% numbers of the Freiburg speech test.

Extractions reveal specific argentophilic proteins in rat and bull sperm heads. Silver-stainability (argentophilia) of cytoplasmic structures occurring in spermatids have been localized into the organizing perinuclear theca, but the biochemical nature and structural associations of these proteins with the cytoskeletal and membranous elements are unresolved and, therefore, were the aim of the present study. Light and electron microscopic analysis of the silver-stainability in the rat spermatids and spermatozoa was carried out in the intact testis tissue and epididymal spermatozoa and after their chemical and mechanical extraction. Correlation of argentophilia with specific proteins of rat and bovine spermatids and spermatozoa was investigated using a recently developed technique for silver nitrate staining of proteins on nitrocellulose. Sequential formation of the silver-stainable domains seemed to proceed from the argentophilic acrosomal ring. Various extractions indicated that argentophilia in the spermatids and spermatozoa was mainly associated with the perinuclear theca and to some extent to the plasma membrane. Hyamine-soluble extract from spermatozoa of rat and bull revealed only a single argentophilic protein of 130 kDa. Hyamine and SDS-soluble extracts of rat testis tissue contained an additional group of argentophilic polypeptides of lower molecular weight (115, 94, 36, 23, and 21 kDa). Reduction in the number of argentophilic proteins appears to be involved in a series of changes in the cyto-architecture of developing spermatids. Tentative cytoskeletal nature of argentophilic proteins remains to be identified. Nevertheless, they may have important physical relations with the higher-order organization of the sperm head cytoskeleton and overlying membranes.

Moderate exercise training modulates cytokine profile and sleep in elderly people. Aging causes several physiological alterations, including alterations in sleep. It is possible that difficulty sleeping can be exacerbated by increased inflammation in older individuals. Moderate exercise training may be a modality of non-pharmacological treatment for sleep disorders and inflammation. We aimed to assess the effects of moderate exercise training on sleep in elderly people as well as their cytokine profiles. Additionally, we examined the effect of exercise training on quality of life parameters using a SF-36 questionnaire. Twenty-two male, sedentary, healthy, elderly volunteers performed moderate training for 60 min/day, 3 days/week for 24 week at a work rate equivalent to their ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2°C, with a humidity of 60 ± 5%. Blood and polysomnograph were collected twice: at baseline (1 week before training began) and after 6 months of training. Training increased aerobic capacity parameters (p<0.0001), decreased REM latency (p<0.02), and decreased time awake (p<0.05). After training, the levels of IL-6 (p<0.0001) and TNF-α (p<0.0001) and the ratio of TNF-α/IL-10 (p<0.0001) were decreased, whereas IL-10 levels were increased after training (p<0.001). Furthermore, exercise training was shown to improve quality of life parameters. Our results suggest that 6 months of training can improve sleep in the elderly and is related to the anti-inflammatory effect of moderate training, which modifies cytokine profiles.

Infectious diseases and the dental office. Dentists and other health care workers have long been concerned about a variety of infectious agents that may be transmitted within the dental setting. In recent years there has also been widespread concern among the general public. Many infectious diseases, including HIV, hepatitis, tuberculosis and syphilis, are important both because of their potential transmissibility and because the first manifestations of the disease may appear in the oral cavity. A knowledge of these diseases will allow the practitioner to recognize associated lesions and also to take appropriate steps to minimize the risk of transmission in the dental office.

Trends and predictors of length of stay after primary percutaneous coronary intervention: a report from the CathPCI registry. Post hoc analyses of clinical trials suggest that certain patients are eligible for early discharge after ST-segment elevation myocardial infarction. The extent to which ST-segment elevation myocardial infarction patients are discharged early after primary percutaneous coronary intervention (PPCI) in current practice is unknown. We examined 115,113 patients in the CathPCI Registry to assess temporal trends in length of stay (LOS) after PPCI. Baseline characteristics were compared between patients with LOS ≤2 and >2 days. Predictors of LOS >2 days were determined by logistic regression and adjusted for clustering among centers. Patterns of discharge within 2 days for low-risk patients with no inhospital complications were examined. From January 2005 through March 2009, mean LOS (4.0 ± 3.0 to 3.6 ± 2.7 days) (P for trend <.001) and the proportion of patients discharged after 2 days decreased (72.0%-65.9%), while predicted inhospital mortality risk remained unchanged. Patients with LOS >2 days (n = 77,471; 67.3%) were older and more likely to have had an intra-aortic balloon pump, cardiogenic shock, transfusions, and post-PPCI complications. Of 958 hospitals, 437 (45.6%) discharged at least half of their low-risk patients with no inhospital complications within 2 days. While the predicted risk profile has remained stable, there has been a significant decrease in LOS after PPCI. Nevertheless, hospitals vary in discharging low-risk and uncomplicated patients early. Discharge within 2 days was associated with specific patient, procedure, and hospital factors. Further study is needed to determine the safety of early discharge among patients undergoing PPCI.

Cross-sectional study on health and social status of the oldest old patients at home care in Belgrade. In the period of the last 50 years important changes in the age structure of the population in Serbia occurred. There was a very pronounced tendency of the total demographic aging of the population. The main aim of the Study is evaluation of basic health, functional and social status of the elderly patients (N = 645) admitted in Institute of Gerontology, Home Treatment and Care (IGHTC) Belgrade in 2001. Particular attention has been paid to the health and social status of the "oldest old" (90+ age) patients in comparing to the group of the "young old" (60-74 age). The purpose is to explore specific health and social need of the oldest old patients, which determine requirements for home care and could present risk factors for their institutionalization. Results can help in health promotion and preventive health care of the oldest old. The results show significantly smaller degree of utilization of health care services in the population of age 90+. We may raise the question of reason for this: the discrimination of the "oldest old" patients in the health security system, unavailability because of functional dependence and non-adjusted system of health care to the oldest patients. This fact confirms the importance of home care services. Home care services, not only contribute to the maintaining quality of life in the old age, but delay and/or prevent institutionalization of patients who are under greatest risk of this. This is for sure one step towards the rationalization of health care costs.

Experimental alcoholic skeletal muscle myopathy is characterised by a rapid and sustained decrease in muscle RNA content. An investigation was made into the effects of ethanol feeding (36% of total calories) on skeletal muscle. From 7 to 42 days, muscle weights and protein and DNA contents of alcohol-treated rats were significantly lower (10-23%) than pair-fed controls (with glucose as 36% of total calories). Ethanol feeding markedly reduced muscle RNA content by 22-34%, when compared to controls. Muscle RNA content of ethanol-fed rats at 7, 14, 28 and 42 days of treatment was significantly lower than initial values (i.e. at 3 days) by 22-38%. Thus, ethanol feeding caused an initial net loss and thereafter a reduction in the rate of accretion of RNA. The marked and sustained loss in the muscle protein synthetic apparatus may be a precipitating event in the development of experimental skeletal muscle myopathy.

Localization of oestrogen receptors in the epididymis during sexual maturation of the domestic cat. Oestrogens are involved in regulation of spermatogenesis and sperm maturation and are essential for male fertility. To study the role of oestrogens on epididymal function in the domestic cat, we analyzed the localization patterns of oestrogen receptors (ERs) within the epididymis of juvenile, pubertal and adults using immunohistochemistry. Cat epididymal tissues obtained during routine castrations were fixed in chilled Bouin's solution and processed for immunohistochemistry with ER-specific antibodies. For a certain receptor type, ER localization was influenced by donor age. In the juvenile epididymis, ERalpha was localized in the nuclei of epithelial cells of efferent ducts and undifferentiated epithelium of the ductus epididymis. During puberty, ERalpha localization in the undifferentiated epithelium of the epididymis shifted from the nuclei to the cytoplasm and plasma membrane. Oestrogen receptor-alpha level was highest in the pubertal and adult epididymis, especially within the cytoplasm and in plasma membranes of caput epithelial cells. This finding was suggestive of a role in fluid reabsorption within the efferent ducts and the epididymis. In corpus and cauda regions, ERalpha was less abundant, suggesting a minor role for oestrogens in sperm storage areas. Interestingly, localization of ERbeta was neither influenced by age nor location within the epididymis and was ubiquitous throughout. Results demonstrate that oestrogen actions within the epididymis may be predominantly mediated through ERalpha during sexual maturation in the domestic cat.

[Intake of fermented milk containing Lactobacillus casei DN-114 001 and its effect on gut flora]. To study the gut flora in infants who received fermented milk containing Lactobacillus casei and Streptococcus termophilus and its effect on secretory immunoglobulin levels. An experimental, randomized, prospective, parallel group study was carried out. Thirty-five infants were included (18 in the treatment group and 17 in the control group) with a mean age of 2 years (SD: 0.6 years; range: 1-3 years). The experimental group received both fermented milk (0.5 l/day) containing L. casei and S. termophilus for 6 weeks and standard cow's milk for the following 6 weeks. The control group received standard cow's milk (0.5 l/day) for 12 weeks. Secretory IgA levels in saliva were evaluated in the experimental group at the start of the study (baseline levels) and 6 weeks later. In both groups, stools were collected to study gut flora at 0, 6 and 12 week. Secretory IgA levels significantly increased (p =0.0063) from a mean baseline value of 2.5 mg/dl to a mean of 3.4 mg/dl at 6 weeks. Gram-negative aerobic flora were decreased in the experimental group after 6 weeks compared with the control group (p =0.0203). The number of infants with Lactobacillus spp in their gut flora was greater in the experimental group than in the control group at week 6 and this difference was statistically significant (p =0.028) at week 12. Conclusion The present study provides evidence of L. casei survival in the gastrointestinal tract and of its effect of increasing secretory IgA.

Symptomatic hypokalaemia and rhabdomyolysis due to excessive and long-term soft drink consumption: a case report. A 35-year-old man was admitted to the emergency room with the complaint of weakness of the extremities, which abruptly began in the morning. Only mild generalized muscle weakness was present on physical examination. Laboratory data showed hypokalaemia, elevation of creatinine phosphokinase and serum transaminases. He had been consuming 2.5 litres of soft drink per day for 20 years. There could not be found any metabolic, organic, traumatic and/or pharmacological reason to cause hypokalaemia and rhabdomyolysis other than the long-term and excess consumption of soft drinks. The patient was cured by the replacement of electrolytes and the avoidance of drinking soft drinks.

Amenorrhoea, sterility and hyperprolactinaemia. Importance of complex movement tomographic x-ray study and follow-up of the sella turcica. In a 24 y.o. woman complaining of primary amenorrhoea and infertility, hyperprolactinaemia and clearly enlarged sella turcica on standard x-rays in 1975 led to the diagnosis of a pituitary prolactin-producing adenoma, later confirmed surgically. Galactorrhoea never occurred spontaneously and could not be provoked at physical examination. In the course of a previous investigation in 1967, the standard x-ray of the sella turcica, although showing already a minor duplication of the anterior wall of the sella, had been misinterpreted as being normal. It is clear from the present observation that repeated, for example at yearly intervals, radiological examinations and prolactin determinations (not available before 1971) would allow an early diagnosis. It is furthermore stressed that a tomographic radiological examination using complex movement (spiral or hypocycloidal) should be mandatory in any case of amenorrhoea with hyperprolactinaemia in order to assess or not the possible existence of a prolactin-producing pituitary adenoma. Indeed, dynamic studies of anterior pituitary secretions cannot allow a differential diagnosis between tumoural and functional hyperprolactinaemia.

Cost reduction and outcome improvement in the intensive care unit. Decreasing reimbursement provided by third-party payors necessitates reduction of costs for providing critical care services. If academic medical centers are to remain viable, methods must be instituted that allow cost reduction through practice change. We used short cycle improvement methodology to rapidly achieve these goals. Short cycle improvement methodology involves identifying the areas for improvement, defining a mechanism to evaluate outcome, initiating an improvement plan on a small number of patients, and repeating the cycle with new adjustments based on outcome. Baseline data on areas for improvement was prospectively collected, and protocols to initiate change were developed and tested by short improvement cycles. Outcomes were evaluated, protocols were modified, and another cycle was performed. This methodology was continued until the desired goals had been achieved. To adjust outcomes for severity of illness, Acute Physiology and Chronic Health Evaluation II methodology was used. Using this methodology, we focused on three areas for improvement. Standing orders for laboratory studies, electrocardiograms, and chest x-ray films were eliminated. Protocols were developed for the appropriate use of sedation, analgesics, and neuromuscular blocking agents. Finally, a protocol for weaning from mechanical ventilation was developed to allow respiratory therapists to proceed through the weaning process, which was ordered by a physician. Laboratory tests were reduced by 65% (from 510 to 180 tests per day) with an annual cost savings of $21,593. Chest x-ray reduction of 56% resulted in an annual savings of $3,941. There was a 75% reduction in cost of neuromuscular blocking agents. The use of neuromuscular blocking agents resulted in a 75% reduction in drug costs. Ventilator hours were reduced by 35% from 140 to 90 hours. The average length of overall intensive care unit stay was reduced by 1.5 days (5.0 to 3.5 days). The cost per patient day decreased with an annualized cost savings of 4% per patient day. Unexpected outcomes included a reduction in intensive care unit days from 54 days at baseline to 7 days at the 6-month interval. The infection rates for blood stream infections, urinary tract infections, and nosocomial pneumonia were reduced. Using national nosocomial infection data, these rates represented a reduction from the fiftieth percentile to the twenty-fifth percentile for all measured indicators. Acute Physiology and Chronic Health Evaluation II scores were 19.54 at baseline and increased to 21.2 (p = 0.001) at the 6-month interval. Mortality rates were 16.7% at baseline and were 17.6% (p = 0.89) at the 6-month interval. We concluded that utilization of short cycle improvement methodology provided an ongoing method for reducing costs of critical care services in our patient population with no change in mortality.

Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia. The development of myeloid malignancies is a concern when administering thrombopoietin receptor (or the myeloproliferative leukemia virus proto-oncogene product, MPL) agonists. Progression from myelodysplastic syndrome (MDS) to acute myelogenous leukemia [AML, 9 (6.12%) AML patients among 147 MDS subjects] was reported in a clinical trial. However, only one (0.15%) case of AML among 653 immune thrombocytopenic purpura (ITP) subjects was reported. Our objective was to determine whether there is currently a safety signal in the FDA files termed Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for AML in ITP patients who receive MPL agonists. We conducted a case-controlled study using the FAERS as a source of case and control data. We compared demographic characteristics, such as gender, age and exposure to MPL agonists between AML patients and others among ITP subjects registered between 2002 and 2011. Total of 4,821 ITP subjects were identified, including 62 AML patients. The number of patients treated with romiplostim and eltrombopag was 54 (1.74%) AML patients among 3,102 ITP subjects and nine (1.52%) AML patients among 594 ITP subjects, respectively. It should be noted that all AML patients were exposed to one or more MPL agonists. Another factor associated with AML was male gender. We herein report an association between AML and MPL agonist use in ITP subjects. Due to various biases and the incompleteness of the FAERS data, further studies are warranted to determine whether the detected signal is a real risk. Physicians should not alter their prescribing behaviors based on this single preliminary analysis.

The Relationship of Repeated Technical Assistance Support Visits to the Delivery of Positive Health, Dignity, and Prevention (PHDP) Messages by Healthcare Providers in Mozambique: A Longitudinal Multilevel Analysis. Positive health, dignity, and prevention (PHDP) is Mozambique's strategy to engage clinicians in the delivery of prevention messages to their HIV-positive clients. This national implementation strategy uses provider trainings on offering key messages and focuses on intervening on 9 evidence-based risk reduction areas. We investigated the impact of longitudinal technical assistance (TA) as an addition to this basic training. We followed 153 healthcare providers in 5 Mozambican provinces over 6 months to evaluate the impact of on-site, observation-based TA on PHDP implementation. Longitudinal multilevel models were estimated to model change in PHDP message delivery over time among individual providers. With each additional TA visit, providers delivered about 1 additional PHDP message ( P < .001); clinicians and nonclinicians started at about the same baseline level, but clinicians improved more quickly ( P = .004). Message delivery varied by practice sector; maternal and child health sectors outperformed other sectors. Longitudinal TA helped reach the programmatic goals of the PHDP program in Mozambique.

Does rat liver Golgi have the capacity to synthesize phospholipids for lipoprotein secretion? Phosphatidylcholine and phosphatidylethanolamine in lipoproteins secreted from cultured rat hepatocytes are derived from specific biosynthetic pools (Vance, J. E., and Vance, D. E. (1986) J. Biol. Chem. 261, 4486-4491). We have tested the hypothesis that some of the phospholipids destined for secretion with lipoproteins may be made in the Golgi. Golgi fractions were prepared by three different procedures. Although each procedure yielded membranes highly enriched in galactosyltransferase, the protein profiles on polyacrylamide gels were distinct for each preparation. Similarly, the presence of phospholipid synthetic enzyme activities differed among the preparations of Golgi. Two of the preparations were judged to be contaminated by no more than 15% with endoplasmic reticulum. Although an unequivocal conclusion that Golgi contains phospholipid biosynthetic enzymes is not possible, the available evidence is consistent with this hypothesis. Golgi prepared by one method (Croze, E. M., and Morré, D. J. (1984) J. Cell. Physiol. 119, 46-57) was studied in detail. This preparation contained activities for CTP:phosphocholine cytidylyltransferase, CDP-choline:1,2-diacylglycerol cholinephosphotransferase, CDP-ethanolamine:1,2-diacylglycerol ethanolamine-phosphotransferase, phosphatidylethanolamine-N-methyltransferase, and phosphatidylserine synthase. These enzyme activities in the Golgi displayed properties similar to the enzyme activities in endoplasmic reticulum with respect to Km values for substrates, pH optima, cofactor requirements, and inhibition by metabolites. Topology experiments suggested that these enzymes on endoplasmic reticulum and Golgi are all exposed to the cytosolic surface. Phosphatidylserine decarboxylase was not detected in the Golgi preparation. The results support the hypothesis that Golgi has the capacity to make certain phospholipids for lipoprotein secretion: phosphatidylcholine via the CDP-choline and methylation pathways, phosphatidylethanolamine by the CDP-ethanolamine pathway, and phosphatidylserine. Synthesis of phosphatidylethanolamine via decarboxylation of phosphatidylserine does not appear to occur in Golgi.

Prophylaxis and treatment of deep vein thrombosis in general surgery. Patients undergoing general surgery present an inherent risk of deep vein thrombosis (DVT). Evidence-based strategies for prevention and treatment of DVT should be continuously upgraded on the basis of good-quality recent trials. Articles were identified using MEDLINE, EMBASE, and the Cochrane Library databases (January 1980 to July 2003). Randomized clinical trials and meta-analyses in which different prophylactic and treatment methods were compared for general surgery patients were selected. In general surgery, low-molecular weight heparins (LMWHs) are relied upon more and more for prophylaxis and initial anticoagulant treatment of DVT, because of their multiple advantages in efficacy, safety, and convenience in handling. For cost-effective reasons, full-dose vitamin K antagonists are still preferred as the standard long-term anticoagulation method, while LMWHs represent the exception. Long-term use of low-intensity warfarin should be considered a new standard of care for the management of venous thrombosis. Compared to LMWH, the new anticoagulant molecules fondaparinux and ximelagatran seem to have similar efficacy in the treatment of venous thromboembolism, but they have a 2-fold increased efficacy in its prophylaxis. Clinical implementation of these new anticoagulant molecules depends on their cost-effectiveness; however, they have the potential to become the treatment of choice in the next decade. Thrombolysis has an unacceptable risk of hemorrhagic complications when used in the treatment of postoperative DVT. Furthermore, there are no data to prove that thrombolysis reduces the incidence of postthrombotic syndrome (PTS), despite early and complete recanalization achieved by thrombolysis. Surgical thrombectomy is only meant to decompress the venous hypertension consecutive to massive thrombosis (phlegmasia cerulea dolens) and thus to avoid venous gangrene. Other mechanical percutaneous thrombectomy devices are under evaluation. In selected cases, a combination treatment consisting of locoregional thrombolysis of the crurofemoral venous axis and mechanical thrombectomy of the pelvic venous axis achieves high rates of complete desobliteration.

Integration of health care delivery. Report of a WHO Study Group. WHO defines health by use of the term "well-being". Many people have a more limited view, however, seeing health as no more than the absence of illness. This limited view is reflected in the various "vertical" programmes that aim to combat a specific disease or carry out a particular medical intervention. The achievements of vertical programmes have been tremendous in eradicating or reducing disease. But there remains the obvious but very important problem that a programme that deals with one disease has but limited effect when health is influenced by a range of different factors. Health care has to be provided in an integrated manner if it is to have maximum impact in raising health standards. This report by the WHO Study Group on Integration of Health Care Delivery is a frank assessment of ways to achieve a more holistic approach to health promotion and care. This means not just bringing together different elements of the health system but also strengthening health-related activities in other sectors. The report looks at ways countries have tried to do this-some successful and some not so successful. The report proposes a model of an integrated district health care system. It is a model in which different levels of health care and different approaches to health care both coexist and complement each other. A detailed plan of action contains guidelines for health care integration at district, as well as national and international, levels. The report will be useful for policy-makers, planners and all who have responsibility for organizing a health care system that most fully meets the needs of the whole community.

Denosumab, a RANK ligand inhibitor, for postmenopausal women with osteoporosis. To review the evidence for use of denosumab for the treatment of postmenopausal osteoporosis. A search of MEDLINE and EMBASE databases was conducted during January 2012, using the terms denosumab and osteoporosis, with index dates of 2000 to 2011. Additional information was gathered from Amgen and references cited in articles retrieved. English-language articles including clinical trials involving denosumab for treatment of osteoporosis and review articles were reviewed. Articles using denosumab in males or as treatment for conditions other than osteoporosis or osteopenia were excluded. Many clinical trials have supported the safety and efficacy of denosumab in postmenopausal women with bone loss. It has been shown to improve bone mineral density, decrease markers of bone turnover, and prevent new vertebral fractures. It shows improvement over placebo in studies and has at least similar efficacy to alendronate in measurements of bone mineral density, with less risk for osteonecrosis of the jaw and atypical fracture, but with an increased risk of infections and neoplasms. European cost-effectiveness studies have also demonstrated that denosumab is a cost-effective choice compared to risedronate and no treatment for fracture prevention for postmenopausal women with osteoporosis. Denosumab has demonstrated efficacy and safety as a first-line treatment for postmenopausal osteoporosis in multiple clinical trials over at least 6 years. It may be most cost-effective for women who are unable or refuse to take bisphosphonate drugs.

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis. The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better understanding of the immunologic changes in M. tuberculosis infection and the development of new strategies for diagnosis and prevention of tuberculosis.

[Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia]. Clinical effects of KRN8601 (recombinant human granulocyte colony-stimulating factor:rhG-CSF) were studied in 26 patients with chronic neutropenia including 4 Kostmann's disease, 1 Shwachman's syndrome, 1 Lonsdale's syndrome, 1 glycogen storage disease Ib-associated, 6 chronic benign, 5 chronic hypoplastic, 2 cyclic, 4 autoimmune and 2 miscellaneous neutropenia. The patients were given rhG-CSF intravenously at doses of 20-540 micrograms/m2 or subcutaneously at doses 20-400 micrograms/m2, over the periods of 2-32 weeks. Increases in neutrophil counts occurred after rhG-CSF administration in 23 of the 26 patients. Patients with Kostmann's disease, Shwachman's syndrome and chronic hypoplastic neutropenia responded poorly compared to patients with other types of neutropenia. There were no serious side effects which caused interruption of the study. These results indicated a beneficial effect of KRN8601 in various types of chronic neutropenia.

Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons. The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts in the thalamus and thus plays an important role in regulating the excitability of the thalamocortical network. Inhibition occurs through GABAergic synapses on relay cells as well as through GABAergic synapses between reticularis neurons themselves. Here we report that the role and mechanisms of this inhibition, which frequently have been studied using N-methyl derivatives of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the whole cell patch-clamp technique in thalamic slices from young rats, we observed an enhancement by bicuculline methiodide, methobromide, and methochloride (collectively referred to as bicuculline-M; 5-60 microM) of the low-threshold calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin (1 microM) and was not reproduced in picrotoxin (100-300 microM). The effect did not involve activation of any GABA receptor subtype. Voltage-clamp recordings showed that bicuculline-M blocked the current underlying the low-threshold spike burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100 nM). Recordings from nucleated patches extracted from reticularis neurons demonstrated that this effect was not mediated by modulation of the release of an unidentified neurotransmitter but that bicuculline-M directly blocks small conductance (SK) channels. The AHP-blocking effect also was observed in other brain regions, demonstrating that although bicuculline-M is a potent GABAA receptor antagonist, it is of limited value in assessing GABAergic network interactions, which should be studied using picrotoxin or bicuculline-free base. However, bicuculline-M may provide a useful tool for developing nonpeptide antagonists of SK channels.

Understanding charge trapping/detrapping at the zinc oxide (ZnO)/MAPbI3 perovskite interface in the dark and under illumination using a ZnO/perovskite/ZnO test platform. We fabricated a zinc oxide (ZnO)/methylammonium lead iodide (MAPbI3) perovskite/ZnO field effect transistor (FET) test platform device through which ZnO/perovskite interfacial contact properties can be probed in the dark and under illumination. Using pulsed laser deposition, highly conductive (0.014 Ω cm) ZnO source and drain electrodes were fabricated allowing for the investigation of the interfacial charge transfer properties through current-voltage characteristics of a ZnO/perovskite/ZnO FET. With a bottom-contact FET device, gate voltage dependent current hysteresis in the drain current-gate voltage curves was probed at low temperature to minimize the effect of ion migration on electronic charge transport in the perovskite layer. Under illumination, importantly, ZnO/perovskite electrical contact properties were significantly altered due to electronic energy barrier change at the interface arising from the detrapping of electrons from the ZnO/perovskite interface, resulting in an enhanced dark current and a suppressed photocurrent. The origin of current hysteresis in the ZnO/perovskite/ZnO FET device is discussed relating it to interfacial charging/discharging associated with ultraviolet (UV)-induced oxygen adsorption/desorption. The results presented herein demonstrate that interfacial electronic properties at the donor (perovskite)/acceptor (ZnO) interface can be altered by photoinduced carrier trapping/detrapping, providing insights that UV-induced persistent photoconduction in transition metal oxide electron transport layers including ZnO may be contributing to the current hysteresis observed in the perovskite photovoltaic devices.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus. Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.

Involvement of a cytochrome P450 system in microsomal debromination of alpha-(bromisovaleryl)urea. The reductive debromination of a hypnotic, (alpha-bromisovaleryl)urea to (3-methylbutyryl)urea by rat liver microsomes was studied. Pretreatment of rats with cytochrome P450 inducers such as phenobarbitone, 3-methylcholanthrene, acetone and pregnenolone-16 alpha-carbonitrile enhanced the debromination of (alpha-bromisovaleryl)urea by liver microsomes. Microsomal debromination was inhibited by cytochrome P450 inhibitors such as metyrapone, alpha-naphthoflavone, SKF 525-A and carbon monoxide. Microsomal debromination was enhanced by addition of NADPH-cytochrome P450 reductase and inhibited by addition of an antibody against the flavo enzyme to the liver microsomes. A reconstituted cytochrome P450 system containing NADPH-cytochrome P450 reductase, and cytochrome P450 1AI or P450 2BI exhibited debrominating activity toward the hypnotic. These results indicated that a cytochrome P450 system plays an essential role in the microsomal debromination of (alpha-bromisovaleryl)urea.

Discovery of Metabolic Biomarkers Predicting Radiation Therapy Late Effects in Prostate Cancer Patients. Patients presenting with prostate cancers undergo clinical staging evaluations to determine the extent of disease to guide therapeutic recommendations. Management options may include watchful waiting, surgery, or radiation therapy. Thus, initial risk stratification of prostate cancer patients is important for achieving optimal therapeutic results or cancer cure and preservation of quality of life. Predictive biomarkers for risks of complications or late effects of treatment are needed to inform clinical decisions for treatment selection. Here, we analyzed pre-treatment plasma metabolites in a cohort of prostate cancer patients (N = 99) treated with Stereotactic Body Radiation Therapy (SBRT) at Medstar-Georgetown University Hospital in a longitudinal, quality-of-life study to determine if individuals experiencing radiation toxicities can be identified by a molecular profile in plasma prior to treatment. We used a multiple reaction mass spectrometry-based molecular phenotyping of clinically annotated plasma samples in a retrospective outcome analysis to identify candidate biomarker panels correlating with adverse clinical outcomes following radiation therapy. We describe the discovery of candidate biomarkers, based on small molecule metabolite panels, showing high correlations (AUCs ≥ 95%) with radiation toxicities, suitable for validation studies in an expanded cohort of patients.

Total hip arthroplasty: optimal treatment for displaced femoral neck fractures in elderly patients. Although internal fixation is recommended for most nondisplaced fractures of the femoral neck, the optimal treatment for displaced fractures of the femoral neck is controversial. Options for operative treatment of displaced fractures of the femoral neck include: reduction and internal fixation; unipolar hemiarthroplasty; bipolar hemiarthroplasty; and total hip arthroplasty. One hundred eighty-six displaced fractures of the femoral neck in elderly patients were treated surgically with internal fixation (in 120 patients), hemiarthroplasty (in 43 patients), and total hip arthroplasty (in 23 patients). One hundred twenty patients with displaced fractures treated with internal fixation were compared with 66 patients with displaced fractures treated with arthroplasty. Criteria for comparison were reoperation, mortality, hospital discharge disposition, functional outcome, living status, and cost effectiveness. There was no difference in rates of reoperation or mortality, but arthroplasty produced a longer interval to reoperation or death. Arthroplasty was associated with more independent living, and arthroplasty was more cost-effective than internal fixation. Total hip arthroplasty was the best treatment for displaced fractures of the femoral neck in elderly patients in this series.

Inhibiting p90 ribosomal S6 kinase prevents (Na+)-H+ exchanger-mediated cardiac ischemia-reperfusion injury. Pharmacological and genetic studies indicate that the (Na+)-H+ exchanger isoform 1 (NHE1) plays a critical role in myocardial ischemia and reperfusion (I/R) injury. We found that p90 ribosomal S6 kinase (RSK) phosphorylated serine 703 of NHE1, stimulating 14-3-3 binding and NHE1 activity. Therefore, we hypothesized that inhibiting RSK in cardiomyocytes would prevent NHE1 activation and decrease I/R-mediated injury. To examine the role of RSK in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative RSK (DN-RSK-TG). DN-RSK-TG hearts demonstrated normal basal cardiac function and morphology. However, myocardial infarction (left coronary artery occlusion for 45 minutes) in DN-RSK-TG hearts was significantly reduced at 24 hours of reperfusion from 46.9+/-5.6% area at risk in nontransgenic littermate controls to 26.0+/-4.2% in DN-RSK-TG (P<0.01). Cardiomyocyte apoptosis was significantly reduced after I/R in DN-RSK (0.9+/-0.2%) compared with nontransgenic littermate controls (6.2+/-2.6%). Importantly, activation of RSK and interaction of 14-3-3 with NHE1, necessary for agonist-stimulated NHE1 activity, were increased by I/R and inhibited by 70% in DN-RSK-TG (P<0.01). Next, we transduced rat neonatal cardiomyocytes with adenovirus-expressing DN-RSK (Ad.DN-RSK) and measured NHE1 activity. The baseline rate of pH recovery in acid-loaded cells was equal in cells expressing LacZ or DN-RSK. However, NHE1 activation by 100 micromol/L H2O2 was significantly inhibited in cells expressing DN-RSK (0.16+/-0.02 pH units/min) compared with Ad.LacZ (0.49+/-0.13 pH units/min). Apoptosis induced by 12 hours of anoxia followed by 24 hours' reoxygenation was significantly reduced in cells expressing Ad.DN-RSK (18.6+/-2.0%) compared with Ad.LacZ (29.3+/-5.4%). In summary, RSK is a novel regulator of cardiac NHE1 activity by phosphorylating NHE1 serine 703 and a new pathological mediator of I/R injury in the heart.

Histochemical differences within the ciliary muscle and its function in accommodation. During accommodation, the ciliary muscle is known to move forward-inward. This movement depends on the stiffness of the ciliary muscle connections with the scleral spur. These connections are mediated by the tips of the meridional muscle. If the tips are weakened by pharmacological or surgical means, accommodation suffers. For normal accommodation, it is therefore necessary that the tips stiffen before the contraction of the main part of the muscle. We have therefore looked at the primate eye for enzymatic and ultrastructural differences between the tips and the bulk of the muscle viz, the reticular and circular portion. Myosin ATPase was stained after either alkaline or acid preincubation. Lactate dehydrogenase (LDH), succinic dehydrogenase (SDH), NADH-tetrazoliumreductase (TR) and lipids were stained using conventional methods. The results of the enzyme staining were a modest difference between the meridional tips and the bulk. The tips stained stronger for ATPase following both preincubation methods, and for LDH, whereas the bulk cells stained stronger for SDH, NADH-TR and lipids. The tips contained fewer mitochondria and more myofibrils. In all these respects, the tips of the meridional muscle resemble the fast fibers of striated muscle.

Psychopathology of people with mental handicap and epilepsy. I: Maladaptive behaviour. One hundred and fifty mentally handicapped people (100 from hospital and 50 from the community) with epilepsy were studied along with an individually matched control group of 150 (100 from hospital and 50 from the community) non-epileptic mentally handicapped people. Behaviour was studied using the Profile of Abilities and Adjustment Schedule. Of the total population, 55.3% showed some type of severe behaviour problem. Although the epileptics showed slightly more severe behaviour problems than the non-epileptic group, there was no statistically significant difference between the two groups. Some differences emerged between the groups when subgroups of epileptics were studied.

Thorn: a new approach to mental health training. The Thorn Initiative started life as an educational programme focusing on community psychiatric nurses. From the beginning its teaching has been multidisciplinary and at present its students come from a variety of backgrounds. This article describes the rationale for the initiative and describes its progress and impact on those who experience severe mental health problems and their families.

Combined therapy of polyamine antimetabolites and antitumor drugs for human gastric cancer xenotransplanted into nude mice. Antitumor therapies using polyamine antimetabolites combined with 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3(2-chloroethyl)-3-nitrosourea (ACNU) or fluorinated pyrimidines for human gastric cancer xenotransplanted into nude mice were studied to determine inhibiting post-therapeutic regrowth of the tumor after cessation of antitumor treatments with polyamine antimetabolites alone. ACNU 20 mg/kg, fluorinated pyrimidine, 5-FU 52.8 mg/kg and 5'-deoxy-5-fluorouridine (5'-DFUR) 100 mg/kg as well as polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) 1000 mg/kg and methylglyoxal-bis-guanylhydrazone (MGBG) 50 mg/kg were given intraperitoneally for 5 successive days. When DFMO and MGBG were combined with ACNU, the post-therapeutic regrowth was definitely inhibited, while combined treatments with 5-FU or 5'-DFUR did not inhibit the regrowth. Post-therapeutic DNA biosynthesis was suppressed in mice given DFMO, MGBG plus ACNU. On the contrary, in mice treated with DFMO, MGBG plus 5-FU or 5'-DFUR, suppression of DNA biosynthesis was not observed. Tumor tissue spermine levels in the DFMO, MGBG plus 5-FU or 5'-DFUR group remained unchanged, compared to those in the DFMO + MGBG group. In mice given DFMO, MGBG plus ACNU, however, spermine levels were markedly depressed; and the ACNU alone depressed also the tissue spermine levels. These different results between nitrosourea and fluorinated pyrimidines may relate to mechanisms of action of these antitumor drugs.

Physico-chemical properties of the N-terminally truncated L68Q cystatin C found in amyloid deposits of brain haemorrhage patients. Cystatin C, a major extracellular cysteine proteinase inhibitor, is deposited as amyloid in brain haemorrhage patients with hereditary cystatin C amyloid angiopathy (HCCAA). A disease-causing mutation on the genetic level results in the substitution Leu68-->Gln (L68Q) in cystatin C, which causes protein instability. Besides carrying the L68Q substitution, cystatin C in amyloid deposits isolated from patients is N-terminally truncated by 10 amino acids. To elucidate the role of the N-terminal truncation for protein stability and aggregation properties, (delta1-10,L68Q)-cystatin C was produced in an Escherichia coli expression system and characterised. Unlike wild-type cystatin C, this variant rapidly dimerised under physiological conditions. Two unfolding intermediates of (delta1-10,L68Q)-cystatin C were identified, under the same pH and ionic strength conditions as required to form intermediates of full-length L68Q cystatin C. No evidence was found that the N-terminal truncation per se alters protein stability and leads to higher forms of aggregation. Monomeric as well as dimeric L68Q cystatin C incubated with neutrophil elastase was truncated as in HCCAA patients' amyloid. A protein variant with a thrombin cleavage site placed in front of residue Gly11 in L68Q cystatin C was constructed and used to confirm that the N-terminal segment is similarly accessible to proteinases in the monomeric and dimeric states of L68Q cystatin C. Thus, the N-terminal segment of L68Q cystatin C is exposed to proteolytic attack and does not seem to be involved in intramolecular contacts leading to dimerisation or higher-order aggregation. We conclude that the N-terminal truncation likely is an event secondary to amyloid formation, and of no relevance for the development of HCCAA.

AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing. AhV_aPA, the acidic PLA₂ purified from Agkistrodon halys pallas venom, was previously reported to possess a strong enzymatic activity and can remarkably induce a further contractile response on the 60 mM K⁺-induced contraction with an EC₅₀ in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p-bromo-phenacyl-bromide (pBPB), which can completely inhibit the enzymatic activity of AhV_aPA, did not significantly reduce the contractile response on vessel rings induced by AhV_aPA, indicating that the vasoconstrictor effects of AhV_aPA are independent of the enzymatic activity. The inhibitor experiments showed that the contractile response induced by AhV_aPA is mainly attributed to the Ca²⁺ releasing from Ca²⁺ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca²⁺ release from SR is related to the activation of inositol trisphosphate receptors (IP₃Rs) rather than ryanodine receptors (RyRs). Furthermore, the vasoconstrictor effect could be strongly reduced by pre-incubation with heparin, indicating that the basic amino acid residues on the surface of AhV_aPA may be involved in the interaction between AhV_aPA and the molecular receptors. These findings offer new insights into the functions of snake PLA₂ and provide a novel pathogenesis of A. halys pallas venom.

Association between left ventricular perfusion defects and myocardial deformation indexes in heart transplantation recipients. The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up.

[C-reactive protein in the recognition of postoperative infectious complications]. The postoperative levels of C-reactive protein (CRP) of 384 patients were studied prospectively. Infectious complications occurred in 50 patients. 92% of these patients showed a postoperative CRP increase. The CRP increase could be detected in 67.5% prior to the clinical signs of the septic complication, whereas 32.5% of the patients showed the CRP increase at the time of clinical symptoms. In 8 patients with rising CRP levels no septic focus could be detected. CRP seems to be a helpful parameter in the postoperative management especially in the early diagnosis of septic complications whereas the erythrocyte sedimentation rate and white blood cell count, which were detected simultaneously to CRP, lack reliability concerning early detection of postoperative complications.

Predicted lower limit of normal reduces misclassification risk of airflow limitation in asymptomatic elderly never-smokers. It remains controversial what better defines abnormal lung function at the extremes of age. This study aimed to establish new spirometric reference equations for residents in Jinan and compare the most accepted two spirometric definitions of chronic obstructive pulmonary disease (COPD)-a fixed post-bronchodilator ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) below 70% vs. FEV1/FVC < lower limit of normal (LLN)-in an elderly population (age ≥60 years). Among 10 002 cases, only never-smokers who had no respiratory symptoms or diagnoses of cardiopulmonary diseases and whose lung function measurements strictly followed the American Thoracic Society guidelines, were included in the statistical analysis. For each gender, prediction equations of FEV1, FVC, FEV1/FVC and corresponding LLN values were developed using multiple regression models. In this cross-sectional study, spirometric reference values were statistically derived from a sample of 1328 healthy never-smokers (672 males, 656 females), age 56-84 years. As expected, age and height were the main predictors for all lung function parameters. Using the two spirometric definitions, the number of pulmonary function test results interpreted as obstructed varied markedly in the elderly population for both genders (males: χ(2) = 19.59, P < 0.01; females: χ(2) = 5.67, P = 0.017). The Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion probably leads to overdiagnosis in asymptomatic elderly never-smokers. Our study suggests that the predicted LLN values will reduce the misclassification risk instead. However, cohort studies are urgently needed for clinical validation.

Formation of biocompatible nanocapsules with emulsion core and pegylated shell by polyelectrolyte multilayer adsorption. The aim of this work was to develop a novel method of preparation of loaded nanosize capsules based on liquid core encapsulation by biocompatible polyelectrolyte (PE) multilayer adsorption, with or without pegylated outermost layer. Using AOT (docusate sodium salt) as emulsifier, we obtained cores, stabilized by an AOT/PLL (poly-L-lysine hydrobromide) surface complex. These positively charged cores were encapsulated by layer-by-layer adsorption of polyelectrolytes, biocompatible polyanion PGA (poly-L-glutamic acid sodium salt), and biocompatible polycation PLL. We used the saturation method for formation of consecutive layers, and we determined the optimal conditions concerning concentration of surfactant and polyelectrolytes to form stable shells. The average size of the obtained capsules was 60 nm. Pegylated external layer were prepared using PGA-g-PEG (PGA grafted by PEG poly(ethylene glycol)). The capsules were stable for at least a period of 3 months. These nanocapsules were biocompatible when tested for cytotoxicity in a cellular coculture assay and demonstrated no or very low nonspecific binding to peripheral blood mononuclear cells when tested by flow cytometry. In order to study drug effects on leukemia cells, beta-carotene and vitamin A have been encapsulated as model drugs.

Tumoral calcinosis-like metastatic calcification in a patient on renal dialysis. Tumoral calcinosis-like metastatic calcification in a patient with uremia on dialysis has rarely been reported in the radiological literatures. This report describes the radiographic, scintigraphic, ultrasound, and CT findings of this condition in a 54-year-old man who had a clinical history of renal dialysis for 6 years. Elevation of serum phosphate and parathyroid hormone levels was noted. Physical examination revealed a hard, movable, and tender mass over his left arm. Plain radiographs of the left shoulder showed an amorphous massive calcification in the upper arm. Scintigraphy showed increased tracer accumulation in the soft tissue of the proximal portion of the left arm and both thighs, where CT scan revealed multilocular, amorphous, calcified masses in these areas. Scintigraphy can help in screening multiple lesions, and CT scan may further help in identifying the extent of a localized lesion such as joint involvement. Ultrasound showed localized multiloculated fluid accumulation within hyperechoic masses and perifocal interstitial fluid collection, which can help to determine the activity of the lesion. Ultrasound findings of tumoral calcinosis have not been reported before.

[Inversion of organic matter content of the north fluvo-aquic soil based on hyperspectral and multi-spectra]. The present study aims to assess the feasibility of multi-spectral data in monitoring soil organic matter content. The data source comes from hyperspectral measured under laboratory condition, and simulated multi-spectral data from the hyperspectral. According to the reflectance response functions of Landsat TM and HJ-CCD (the Environment and Disaster Reduction Small Satellites, HJ), the hyperspectra were resampled for the corresponding bands of multi-spectral sensors. The correlation between hyperspectral, simulated reflectance spectra and organic matter content was calculated, and used to extract the sensitive bands of the organic matter in the north fluvo-aquic soil. The partial least square regression (PLSR) method was used to establish experiential models to estimate soil organic matter content. Both root mean squared error (RMSE) and coefficient of the determination (R2) were introduced to test the precision and stability of the modes. Results demonstrate that compared with the hyperspectral data, the best model established by simulated multi-spectral data gives a good result for organic matter content, with R2=0.586, and RMSE=0.280. Therefore, using multi-spectral data to predict tide soil organic matter content is feasible.

Characterization of Immunoglobulin G Bound to Latex Particles Using Surface Plasmon Resonance and Electrophoretic Mobility. The main objective of this work was the investigation of passive adsorption and covalent coupling of a polyclonal IgG and a monoclonal preparation of IgG against HSA, to a carboxyl latex particle. The functional activity of the coupled protein was then assessed by quantitative immunoassays for the antigen. Sensitized particles, with different protein coverage, were fully characterized using a range of different technologies, including electrophoretic mobility (µe), photon correlation spectroscopy, and surface plasmon resonance (SPR). The antibody-labeled particles were studied with respect to electrokinetic behavior in pH and ionic strength titration, stability, antibody functionality, and their perfomance in immunoaggregation reactions. Important differences were observed between the two sets of particle preparations throughout the series of experiments. The differences could be attributed to the coupling of the IgG molecules to the particles by the two different adsorption protocols. When proteins were chemically bound to the polymer surface it was necessary to activate the carboxyl groups with a carbodiimide (CDI) moiety that in our case was positively charged. The differences in characteristics between the adsorbed and the coupled antibody particles are thought to be due to the fact that in the covalent coupling protocol some CDI molecules remained linked to the particles, which altered the average electrical state of the outer layer in comparison with those samples where antibodies were physically adsorbed. On the other hand, the isoelectric point of the monoclonal antibody was lower (5.4 +/- 0.1) than the pI of the polyclonal antisera (6.9 +/- 0.9), which could explain why the IgG-latex complexes created with monoclonal molecules were colloidally more stable at neutral pH than those created with the polyclonal antisera. However, no immunoaggregation of antibody particles by the presence of antigen was found with the former. The use of SPR demonstrated that the equilibrium constants for the antibody-antigen recognition of the two antibody preparations were quite similar (KA polyclonal IgG = 2.8 10(8) M-1; KA monoclonal IgG = 9.5 10(7) M-1). These observations suggest that the lack of aggregation mediated by antigen demonstrated by the monoclonal antibody coupled to the latex particles may be due to this protein recognizing only one epitope in the HSA molecule. However, as the repulsive charge between antibody-latex particles counteracts the attractive forces between the antigen epitope and the antibody paratope, the greatest immunoaggregation was obtained when using latex particle-antibody complex with a low charge density (N) in the external layer. Copyright 1998 Academic Press.

[Effect of prostate volume on the peripheral nerve block anesthesia in prostate biopsy]. To evaluate the anesthetic efficacy of periprostatic nerve block in transrectal ultrasound(TRUS) guided biopsy on different prostate volume. A total of 568 patients received prostate biopsy in Department of Urology, Subei People's Hospital from May 2013 to September 2015 were retrospectively studied. All patients were divided into local anesthesia group and nerve block group according to different way of anesthesia. Then each group was divided into four subgroups(20-40 ml, >40-60 ml, >60-100 ml and >100 ml subgroups) according to different prostate volume range. After being anaesthetized successfully, patients in two groups underwent prostate biopsy, visual analogue scale(VAS) scores, visual numeric scale(VNS)scores and complications were recorded and analyzed. At inter-group and intra-group in local anesthesia group and nerve block group, Mann-Whitney U test of non-parametric analysis and single factor variance analysis were used to compare the VAS scores and the VNS scores respectively, and chi-square test was used to compare the rates of complication. The VAS scores of four subgroups: local anesthesia group: 1.9±0.9, 2.8±1.5, 3.8±2.3 and 5.3±2.5; nerve block group: 1.5±0.7, 2.0±0.8, 2.9±1.7 and 4.2±2.0. The VNS scores: local anesthesia group: 3.4±0.6, 2.9±0.6, 2.7±0.5 and 1.6±0.7; nerve block group: 3.7±0.5, 3.3±0.4, 3.0±0.8 and 2.0±0.7. The VAS scores and the VNS scores had significant differences (Z=-3.637-98.253, all P<0.05) at inter-group or intra-group level. For the complication rates of operation, hematuria, blood, urinary retention were significant differences (F=1.347-15.402, all P<0.05) at intra-group level. But there were no significant differences at inter-group level(P>0.05). Compared with local anesthesia, ultrasound guided prostate peripheral nerve block anesthesia has great analgesic effect and high safety, but for patients with a large prostate volumethe analgesic effect is inefficiency.

Classification of man-made vitreous fibers: Comments on the revaluation by an IARC working group. In 2001, an IARC working group revaluated the carcinogenic risks of man-made vitreous fibers (MMVF). Compared with the IARC evaluation in 1987, the overall evaluations of insulation glass wool, rock (stone) wool, and slag wool were changed from Group 2B to Group 3. These changes ensued from an alteration in the evidence for cancer in humans and in experimental animals: Instead of "sufficient," the evidence for cancer in experimental animals is now looked upon as "limited" if there is a carcinogenic response after intraperitoneal injection but not after recently conducted inhalation experiments. For these studies, it is argued that they did properly address the technological limitations of earlier inhalation experiments. For Maxim and McConnell [Maxim L.D., McConnell E.E., 2001. Interspecies comparisons of the toxicity of asbestos and synthetic vitreous fibers: a weight-of-the-evidence approach. Regul. Toxicol. Pharmacol. 33, 319-342], well-conducted inhalation studies are very sensitive and rats may be more sensitive than humans in detecting the carcinogenic potential of MMVF. However, their arguments are highly questionable. The explanations of the IARC working group for preferring the newer inhalation studies are not sufficiently supported by the published data. Having in mind the higher sensitivity of humans compared to rats after inhalation of asbestos, more emphasis should have been given to the carcinogenic response after intraperitoneal injection.

Uncle Sam wants your EHR. It might not be as glamorous as the mission to the moon, but creating a national health care IT infrastructure could prove as complex and costly. Just how complex, how costly and how long it will take are open to debate, but nearly everyone agrees that achieving that goal should be a national priority and that Americas can-do spirit will prevail.

Effects of zinc supplementation during pregnancy on pregnancy outcome in women with history of preterm delivery: a double-blind randomized, placebo-controlled trial. The aim of this study was to assess the effect of high dose zinc (Zn) supplement during pregnancy in pregnancy outcome in healthy pregnant women with a previous preterm delivery in Isfahan, Iran. A double-blind placebo-controlled randomized clinical trial was conducted between January 2007 and June 2008. Eighty-four pregnant women with a previous preterm delivery age 19 to 35 years were randomly allocated to receive either 50 mg/day Zn as Zn sulfate or placebo from 12 to 16 weeks of gestation till delivery. Pregnancy outcome was assessed in term of incidence of intrauterine growth retardation (IUGR), birth weight, crown-heel length, head circumference, Apgar score, and gestational age at delivery. The mean birth head circumference was higher in Zn supplemented group than in the placebo group (35.0 cm vs. 33.7 cm, P < 0.05). Although gestational age at delivery (37.1 week vs. 36.7 week) and birth weight (2960.6 g vs. 2819.0 g) of babies born in Zn supplemented group was slightly higher than placebo group, it was not statistically significant. No significant differences were seen for infant length, Apgar score, and IUGR. Adding Zn supplementation during pregnancy to routine care of women with a previous preterm delivery had no significant effect on the gestational age at delivery and birth weight but increased the birth head circumference.

Wischnewski spots in fatal burns. The occurrence of Wischnewski spots in fatal hypothermia has been considered an important indicator of reduced core temperatures, its incidence varying between 40 and 100%. Though many human and animal studies have been conducted to study this phenomenon, the underlying mechanisms contributing to the formation of Wischnewski spots are still not clearly understood. They have been largely reported in human deaths occurring from exposure to freezing temperatures. This is the first reported case of Wischnewski spots observed in a case of fatal burns.

Pulp-dentine complex changes and root resorption during intrusive orthodontic tooth movement in patients prescribed nabumetone. Pulpitis, external root resorption, and pain may be experienced during orthodontic movement. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested to control these changes. The purpose of this study was to observe pulp-dentinal reactions, root resorption, tooth pain, and tooth movement after the application of a 4-ounce intrusive orthodontic force to human maxillary first premolars in patients given the NSAID nabumetone. Thirty-four maxillary first premolars were evaluated. A placebo was prescribed to 17 patients after an intrusive force was activated and reactivated for an 8-week period on the right side. The same procedure was repeated on the left side after patients were given nabumetone. Pulp-dentinal reactions and external root resorption were evaluated by histology. Pain and movement were also evaluated. Nabumetone was found to be useful in reducing pulpitis, external root resorption, and pain caused by intrusive orthodontic movement, without altering tooth movement in response to the application of orthodontic force.

Moving from research to practice in the primary care of children with autism spectrum disorders. Autism spectrum disorders (ASD), once thought rare, are now commonly encountered in clinical practice. Academic pediatricians may be expected to teach medical students and pediatric residents about ASD, but most likely received limited exposure to ASD during their training. In recent years, research that informs the clinical guidance provided to pediatricians regarding surveillance, screening, and ongoing management of children with ASD has accelerated. By 24 months of age, children with ASD exhibit delays across multiple domains of development, yet the diagnosis is frequently made much later. Careful developmental surveillance lowers the age of identification of children with ASD. Several screening tools appropriate for use in primary care settings can aid in early identification. Improved surveillance and screening is of benefit because early intensive behavioral intervention has the potential to improve the developmental trajectory of children with ASD. Providing appropriate medical care for children with ASD improves both child and family outcomes. Recent research regarding sleep disturbances, gastrointestinal problems, and epilepsy in children with ASD has led to clinical pathways to evaluate and address these issues within the context of primary care. By being aware of and disseminating these research findings, academic pediatricians can help future and current clinicians improve the care of children with ASD.

Nasal High-Flow Therapy for Preterm Infants: Review of Neonatal Trial Data. Heated, humidified, nasal high-flow (HF) therapy is a promising treatment for preterm infants, and almost certainly has a place in the clinical care of this population. It is only in the last few years that data have become available from randomized trials comparing HF with other noninvasive respiratory support modes, particularly nasal continuous positive airway pressure. This article discusses the evidence for HF use from randomized clinical trials in preterm infants and proposes recommendations for evidence-based practice.

Catastrophic antiphospholipid syndrome. Catastrophic antiphospholipid syndrome is a rapidly progressive life-threatening disease that causes multiple organ thromboses and dysfunction in the presence of antiphospholipid antibodies. A high index of clinical suspicion and careful investigation are required to make an early diagnosis so that treatment with anticoagulation and corticosteroids can be initiated; plasma exchange and/or intravenous immunoglobulins can be added if the life-threatening condition persists. Despite aggressive treatment and intensive care unit management, patients with catastrophic antiphospholipid syndrome have a 48% mortality rate, primarily attributable to cardiopulmonary failure. This article reviews the current information on the etiopathogenesis, clinical manifestations, diagnosis, management, and prognosis of catastrophic antiphospholipid syndrome.