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['Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by epithelial phenotypic changes and fibroblast activation. Based on the temporal heterogeneity of IPF, we hypothesized that hyperplastic alveolar epithelial cells regulate the fibrotic response.', 'To identify novel mediators of fibrosis comparing the transcriptional signature of hyperplastic epithelial cells and conserved epithelial cells in the same lung.', 'Laser capture microscope and microarrays analysis were used to identify differentially expressed genes in IPF lungs. Bleomycin-induced lung fibrosis was evaluated in Mmp19-deficient and wild-type (WT) mice. The role of matrix metalloproteinase (MMP)-19 was additionally studied by transfecting the human MMP19 in alveolar epithelial cells.', 'Laser capture microscope followed by microarray analysis revealed a novel mediator, MMP-19, in hyperplastic epithelial cells adjacent to fibrotic regions. Mmp19(-/-) mice showed a significantly increased lung fibrotic response to bleomycin compared with WT mice. A549 epithelial cells transfected with human MMP19 stimulated wound healing and cell migration, whereas silencing MMP19 had the opposite effect. Gene expression microarray of transfected A549 cells showed that PTGS2 (prostaglandin-endoperoxide synthase 2) was one of the highly induced genes. PTGS2 was overexpressed in IPF lungs and colocalized with MMP-19 in hyperplastic epithelial cells. In WT mice, PTGS2 was significantly increased in bronchoalveolar lavage and lung tissues after bleomycin-induced fibrosis, but not in Mmp19(-/-) mice. Inhibition of Mmp-19 by siRNA resulted in inhibition of Ptgs2 at mRNA and protein levels.']

['Inactivation of Shox2, a member of the short-stature homeobox gene family, leads to defective development of multiple organs and embryonic lethality as a result of cardiovascular defects, including bradycardia and severe hypoplastic sinoatrial node (SAN) and sinus valves, in mice. It has been demonstrated that Shox2 regulates a genetic network through the repression of Nkx2.5 to maintain the fate of the SAN cells. However, the functional mechanism of Shox2 protein as a transcriptional repressor on Nkx2.5 expression remains completely unknown.', 'A specific interaction between the B56δ regulatory subunit of PP2A and Shox2a, the isoform that is expressed in the developing heart, was demonstrated by yeast 2-hybrid screen and coimmunoprecipitation. Western blotting and immunohistochemical assays further confirmed the presence of phosphorylated Shox2a (p-Shox2a) in cell culture as well as in the developing mouse and human SAN. Site-directed mutagenesis and in vitro kinase assays identified Ser92 and Ser110 as true phosphorylation sites and substrates of extracellular signal-regulated kinase 1 and 2. Despite that Shox2a and its phosphorylation mutants possessed similar transcriptional repressive activities in cell cultures when fused with Gal4 protein, the mutant forms exhibited a compromised repressive effect on the activity of the mouse Nkx2.5 promoter in cell cultures, indicating that phosphorylation is required for Shox2a to repress Nkx2.5 expression specifically. Transgenic expression of Shox2a, but not Shox2a-S92AS110A, mutant in the developing heart resulted in down-regulation of Nkx2.5 in wild-type mice and rescued the SAN defects in the Shox2 mutant background. Last, we demonstrated that elimination of both phosphorylation sites on Shox2a did not alter its nuclear location and dimerization, but depleted its capability to bind to the consensus sequences within the Nkx2.5 promoter region.']

['A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temozolomide regardless of AGT activity. The purpose of this study was to determine the role of MMR deficiency in mediating resistance in samples from patients with both newly diagnosed malignant gliomas and those who have failed temozolomide therapy.', 'The roles of AGT and MMR deficiency in mediating resistance in glioblastoma multiforme were assessed by immunohistochemistry and microsatellite instability (MSI), respectively. The mutation status of the MSH6 gene, a proposed correlate of temozolomide resistance, was determined by direct sequencing and compared with data from immunofluorescent detection of MSH6 protein and reverse transcription-PCR amplification of MSH6 RNA.', 'Seventy percent of newly diagnosed and 78% of failed-therapy glioblastoma multiforme samples expressed nuclear AGT protein in > or = 20% of cells analyzed, suggesting alternate means of resistance in 20% to 30% of cases. Single loci MSI was observed in 3% of patient samples; no sample showed the presence of high MSI. MSI was not shown to correlate with MSH6 mutation or loss of MSH6 protein expression.']

['Laboratories traditionally culture toxoplasma tachyzoites in animals for testing and experimental use. This article considers why available cell culture methods are not used more often.', 'To compare HeLa cell culture and animal culture for production of toxoplasma tachyzoites.', 'In 2000 HeLa culture replaced animal culture for continuous production of toxoplasma tachyzoites in the Scottish Toxoplasma Reference Laboratory. The performance of animal culture (1994-1998) was compared with HeLa culture (2004-2008). A PubMed search was carried out for 1998 and 2008 to assess the culture methods used in laboratories.', 'Animal culture was able to produce higher yields of tachyzoites (10(9) from a cotton rat peritoneal harvest compared to 10(7) from a 75 cm(2) cell culture flask) but significantly more HeLa cultures were successful (93% versus 84%; p=0.025). There was no difference in the quality of tachyzoites from animal and HeLa cultures as demonstrated by the high levels of success in the dye test. HeLa culture offered significant advantages in flexibility and control. A review of the literature showed no significant change in the method of culture used in laboratories between 1998 and 2008 (p=0.36).']

['The objective of this study was to increase the spatial and temporal resolution of dynamic 3-dimensional (3D) magnetic resonance imaging (MRI) of lung volumes and diaphragm motion. To achieve this goal, we evaluate the utility of the proposed blind compressed sensing (BCS) algorithm to recover data from highly undersampled measurements.', 'We evaluated the performance of the BCS scheme to recover dynamic data sets from retrospectively and prospectively undersampled measurements. We also compared its performance against that of view-sharing, the nuclear norm minimization scheme, and the l1 Fourier sparsity regularization scheme. Quantitative experiments were performed on a healthy subject using a fully sampled 2D data set with uniform radial sampling, which was retrospectively undersampled with 16 radial spokes per frame to correspond to an undersampling factor of 8. The images obtained from the 4 reconstruction schemes were compared with the fully sampled data using mean square error and normalized high-frequency error metrics. The schemes were also compared using prospective 3D data acquired on a Siemens 3 T TIM TRIO MRI scanner on 8 healthy subjects during free breathing. Two expert cardiothoracic radiologists (R1 and R2) qualitatively evaluated the reconstructed 3D data sets using a 5-point scale (0-4) on the basis of spatial resolution, temporal resolution, and presence of aliasing artifacts.', 'The BCS scheme gives better reconstructions (mean square error = 0.0232 and normalized high frequency = 0.133) than the other schemes in the 2D retrospective undersampling experiments, producing minimally distorted reconstructions up to an acceleration factor of 8 (16 radial spokes per frame). The prospective 3D experiments show that the BCS scheme provides visually improved reconstructions than the other schemes do. The BCS scheme provides improved qualitative scores over nuclear norm and l1 Fourier sparsity regularization schemes in the temporal blurring and spatial blurring categories. The qualitative scores for aliasing artifacts in the images reconstructed by nuclear norm scheme and BCS scheme are comparable.The comparisons of the tidal volume changes also show that the BCS scheme has less temporal blurring as compared with the nuclear norm minimization scheme and the l1 Fourier sparsity regularization scheme. The minute ventilation estimated by BCS for tidal breathing in supine position (4 L/min) and the measured supine inspiratory capacity (1.5 L) is in good correlation with the literature. The improved performance of BCS can be explained by its ability to efficiently adapt to the data, thus providing a richer representation of the signal.']

['Targeting of KIT and platelet-derived growth factor receptor (PDGFR) tyrosine kinases by imatinib is an effective anticancer strategy. However, mutations of the gatekeeper residue (T670 in KIT and T681 in PDGFRbeta) render the two kinases resistant to imatinib. The aim of this study was to evaluate whether sorafenib (BAY 43-9006), a multitargeted ATP-competitive inhibitor of KIT and PDGFR, was active against imatinib-resistant KIT and PDGFRbeta kinases.', 'We used in vitro kinase assays and immunoblot with phosphospecific antibodies to determine the activity of sorafenib on KIT and PDGFRbeta kinases. We also exploited reporter luciferase assays to measure the effects of sorafenib on KIT and PDGFRbeta downstream signaling events. The activity of sorafenib on interleukin-3-independent proliferation of Ba/F3 cells expressing oncogenic KIT or its imatinib-resistant T670I mutant was also tested.', 'Sorafenib efficiently inhibited gatekeeper mutants of KIT and PDGFRbeta (IC(50) for KIT T670I, 60 nmol/L; IC(50) for PDGFRbeta T681I, 110 nmol/L). Instead, it was less active against activation loop mutants of the two receptors (IC(50) for KIT D816V, 3.8 micromol/L; IC(50) for PDGFRbeta D850V, 1.17 micromol/L) that are also imatinib-resistant. Sorafenib blocked receptor autophosphorylation and signaling of KIT and PDGFRbeta gatekeeper mutants in intact cells as well as activation of AP1-responsive and cyclin D1 gene promoters, respectively. Finally, the compound inhibited KIT-dependent proliferation of Ba/F3 cells expressing the oncogenic KIT mutant carrying the T670I mutation.']

['The presence of secondary hyperparathyroidism is very frequent in the elderly population living in geriatric institutions. It has been associated with an increased mortality rate in previous studies.', 'To evaluate the association of secondary hyperparathyroidism with mortality or hospitalization or both (combined outcome) during a 6-month period in individuals living in geriatric institutions.', 'A cohort of 100 individuals aged between 65 and 102 years living in geriatric institutions in the city of Porto Alegre, Brazil, was prospectively studied. Serum levels of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), albumin, total calcium, phosphorus, magnesium, creatinine and alkaline phosphatase were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault equation. Secondary hyperparathyroidism was defined as serum PTH levels higher than 48 pg/ml and normal or reduced serum calcium levels. The deaths were verified by means of death certificates and hospitalization by the discharge summaries provided by the Brazilian health system hospitals.', 'Fifty-eight percent of the individuals had secondary hyperparathyroidism, defined as serum PTH >48 pg/ml and normal or low serum calcium. Mean serum 25(OH)D levels were 12.5 +/- 8 ng/ml. The odds ratio of an individual with secondary hyperparathyroidism to die, to be hospitalized or to have the combined outcome within 6 months was 6.6 [confidence interval (CI) 95% 0.8-54.6; p = 0.07], 10.7 (CI 95% 1.3-85.9; p = 0.007) and 5.20 (CI 95% 1.10-27.7; p = 0.04), respectively. Secondary hyperparathyroidism and body mass index were independently associated with the combined outcome, after correction for the GFR and 25(OH)D.']

['To verify the values and the time course of regional cerebral blood flow (rCBF) in the cortex located beneath an evacuated acute subdural hematoma (SDH) and their relationship with neurological outcome.', 'rCBF levels were measured in multiple regions of interest, by means of a Xe-computed tomographic technique, in the cortex underlying an evacuated SDH and contralaterally in 20 patients with moderate or severe traumatic brain injury and an evacuated acute SDH. Twenty-three patients with moderate or severe traumatic brain injury and an evacuated extradural hematoma or diffuse injury served as the control group. Outcome was evaluated by means of the Glasgow Outcome Scale at 12 months.', 'Values for the maximum (rCBFmax) and the mean of all rCBF levels in the cortex beneath the evacuated SDH were more frequently consistent with hyperemia. The side-to-side differences in the mean of all rCBF and rCBFmax levels between lesioned and nonlesioned hemispheres were greater in patients with evacuated SDH than in controls (P = 0.0013 and P = 0.0018, respectively). The side-to-side difference in the maximum rCBF value was higher in SDH patients with unfavorable outcomes than in controls at 24 to 96 hours and at 4 to 7 days and higher than in patients with favorable outcomes at 4 to 7 days. The widest side-to-side difference in rCBFmax value was more elevated in patients with an evacuated SDH with unfavorable outcome than in patients with a favorable outcome (P = 0.047), whereas no differences were found in controls. The SDH thickness and the associated midline shift were greater in patients with unfavorable outcomes than in those with favorable outcomes.']

['Phenethyl isothiocyanate (PEITC) is a cancer chemopreventive agent from cruciferous vegetables. Cholangiocarcinoma (CCA) is a chemo-resistant cancer with very poor prognosis. We evaluated the effects of PEITC on induction of apoptotic cell death in relation to cellular glutathione (GSH) and mitochondrial function of a CCA cell line, KKU-M214.', 'Cytotoxic effects of PEITC on a CCA cell line, KKU-M214, and a reference cell line, Chang cells were evaluated. To delineate mechanisms of cell death, the following parameters were measured; GSH and superoxide levels as the oxidative status parameters, apoptosis related proteins levels using Western blotting. Cellular free calcium level and mitochondrial transmembrane potential were also measured.', 'PEITC induced apoptotic cell death of both KKU-M214 and Chang cells. After PEITC treatment, both cells showed decrease of Bcl-xl and increase of Bax levels. While KKU-M214 cells released AIF, Chang cells released cytochrome c, with subsequent activation of caspase 3 and 9, upon PEITC treatment. PEITC induced superoxide formation in both cells, although it seemed not play a role in cell death. PEITC caused GSH redox stress in different ways in two cell types, because N-acetylcysteine (NAC) prevented redox stress in Chang but not in KKU-M214 cells. The loss of mitochondrial transmembrane potential was induced by PEITC concurrent with GSH stress, but was not a primary cause of cell death. The rapid increase of free calcium level in cytosol was associated with cell death in both cell lines. These events were prevented by NAC in Chang cells, but not in KKU-M214 cells.']

['Genetic manipulation of the allograft is an attractive approach to prevent the graft against chronic deterioration through stable expression of immunomodulatory or protective genes. However, the best strategy for prevention of chronic allograft deterioration remains unclear.', 'The efficacies of adeno-associated viral vector-mediated stable expression of indoleamine 2,3-dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G(1) (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of chronic allograft deterioration were compared in a rat heart transplantation model.', 'Transduction of grafts with IL-10 significantly prolonged allograft survival, whereas transduction of grafts with IDO did not improve graft survival compared to controls. Analysis of long-term survived heart allografts showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the development of transplant arteriosclerosis effectively. The suppressive effects of IL-10 in preventing the development of chronic allograft deterioration were associated with lower transcript levels of transforming tumor growth factor beta 1 and macrophage migration inhibitory factor in the graft. In addition, higher transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft.']

['A moderate intake of alcohol is associated with lower cardiovascular mortality, and the role of circulating progenitor cells in the beneficial effect of alcohol on atherosclerosis is unclear. The hypothesis of this study was that alcohol ameliorates atherosclerosis by modulating the circulating levels of stromal cell-derived growth factor (SDF)-1 and vascular progenitor cells.', 'Atherosclerosis was induced by infusion of angiotensin II in apolipoprotein-E deficient mice, which were treated with high and low doses of ethanol for 28 days by intraperitoneal injection. Mice treated with low-dose ethanol had significantly less dilatation and fewer atheromatous lesions than mice receiving the high-dose ethanol. The number of circulating fibrocytes was significantly lower in mice treated with high-dose ethanol compared with mice with atherosclerosis untreated with ethanol. The plasma CXCL12/SDF-1 level was significantly increased in mice treated with low-dose ethanol compared with mice treated with a high dose, and the plasma concentration of transforming growth factor-β1 was significantly increased in mice treated with high-dose ethanol compared with control mice. Ethanol regulated the secretion of SDF-1 and vascular endothelial growth factor from fibroblasts in a dose-dependent and bimodal fashion.']

['Our aim was to investigate serum clusterin levels in preeclampsia and to determine whether any changes in clusterin levels are useful in distinguishing the presence of concomitant intrauterine growth restriction (IUGR) and in predicting adverse pregnancy outcomes.', 'A prospective case-control study was carried out which included 86 pregnant women (47 patients with preeclampsia and 39 healthy controls). Maternal serum samples obtained from all participants and clusterin levels were determined by enzyme-linked immunosorbent assay (ELISA).', 'Compared with controls, women with preeclampsia had significantly higher clusterin levels (mean 83.8±23.6 vs. 119.2±40.5, P<0.01). Further analysis revealed the highest clusterin levels were in patients with preeclampsia and IUGR (P<0.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of clusterin levels for adverse maternal outcomes, the area under the curve (AUC) was 0.738 (95% CI: 0.616-0.859). The best clusterin cut-off value in predicting adverse maternal outcomes was 102.6 pg/mL with 75% sensitivity and 66% specifity. Multivariable logistic regression analysis revealed serum clusterin levels of >102.6 pg/mL was independently associated with preeclampsia (OR: 6.18, 95% CI: 2.41-15.9) and maternal adverse outcomes (OR: 5.13, 95% CI: 2.01-13.1) and also clusterin levels higher than 117.4 pg/mL were associated with adverse neonatal outcomes (OR: 5.02, 95% CI: 1.04-24.3).']

["Neurons project their axons along specific pathways in order to establish appropriate connections with their target cells. The rate and direction of axonal growth is determined by interactions between the highly motile growth cone and environmental cues that can act in either an attractive or a repulsive manner. Locomotion is ultimately dependent upon the reorganisation of the actin cytoskeleton and an established role for the Rho family of small GTPases in regulating this process in non-neuronal cells identifies them as candidate signalling molecules in growth cones. An inactive form of Rac1 has recently been shown to inhibit the 'growth-cone collapse' response induced by chick Sema3A, a protein that has recently been established as an important guidance cue. The molecular basis for this inhibition remains unclear.", 'We have made a series of overlapping peptides from the amino-terminal region of Rac1 and rendered them cell permeable by synthesis in tandem with an established internalisation vector. We report here that a peptide encompassing Rac1 amino acids 17-32 binds directly to the established Rac1-interacting molecules PAK, WASP, 3BP-1 and p85beta(P13K), but not to p67(Phox). Furthermore, the peptide can compete with activated Rac1 for target binding, and inhibits Sema3A-induced growth-cone collapse. We also synthesised cell-permeable peptides that correspond to the Cdc42/Rac1-binding (CRIB) motifs present in PAK and N-WASP. Our results show that a CRIB-containing peptide from PAK, but not that from N-WASP, inhibits growth-cone collapse and that the inhibitory activity correlates with binding to Rac1 and not to Cdc42.']

['Wound healing depends on a well-balanced regulation of inflammation and angiogenesis. In chronic wounds the healing process is disturbed and inflammation persists. Regulation of wound closure is controlled by transmembrane and extracellular proteins, the folding and maturation of which occur in the endoplasmic reticulum (ER) by ER-resident chaperone machinery.', 'To study the role of the ER-resident chaperones BiP/Grp78, its cochaperone Mdg1/ERdJ4, and Grp94 in chronic, nonhealing wounds.', 'Immunohistochemical staining of these chaperones in individual human biopsies and investigation of the possible role of BiP and Mdg1 in endothelial cells, focusing on their inflammatory response and angiogenic potential.', 'In all chronic wounds investigated, the levels of these ER-resident chaperones were elevated in endothelial cells and leucocytes. The proangiogenic role of BiP has been shown in tumour growth studies before and was confirmed in this study. Proangiogenic activity of the cochaperone Mdg1 has been postulated before but could not be confirmed in this study. The chemokine tumour necrosis factor (TNF)-α was shown to trigger the presentation of proinflammatory adhesion molecules and the release of proinflammatory cytokines. Here we show that TNF-α does not affect endogenous chaperone levels, but that the ER-resident chaperones BiP and Mdg1 modulate the cellular TNF-α-induced proinflammatory response.']

['Determination of intracellular signalling pathways that mediate intestinal epithelial proliferation is fundamental to the understanding of the integrity and function of the intestinal tract under normal and diseased conditions. The phosphoinositide 3-kinase (PI3K)/Akt pathway transduces signals initiated by growth factors and is involved in cell proliferation and differentiation. In this study, we assessed the role of PI3K/Akt in transduction of proliferative signals in intestinal epithelial cells.', 'A rat intestinal epithelial (RIE) cell line and human colorectal cancer HCA-7 and LS-174 cell lines served as in vitro models. The Balb/cJ mouse was the in vivo model.', 'PI3K activation was critical for G1 cell cycle progression of intestinal epithelial cells. Ectopic expression of either active p110alpha or Akt-1 increased RIE cell proliferation. In vivo experiments demonstrated that PI3K activation was closely associated with the proliferative activity of intestinal mucosa. Treatment of mice with PI3K inhibitors blocked induction of PI3K activity and attenuated intestinal mucosal proliferation associated with oral intake. Epidermal growth factor and transforming growth factor alpha stimulated PI3K activation which was required for growth factor induced expression of cyclin D1.']

['Salvicine is a novel DNA topoisomerase II inhibitor with potent anticancer activity. In present study, the effect of salvicine against metastasis is evaluated using human breast carcinoma orthotopic metastasis model and its mechanism is further investigated both in animal and cellular levels.', 'The MDA-MB-435 orthotopic xenograft model was applied to detect the antimetastatic effect of salvicine. Potential target candidates were detected and analyzed by microarray technology. Candidates were verified and explored by reverse transcription-PCR and Western blot. Salvicine activities on stress fiber formation, invasion, and membrane translocation were further investigated by immunofluorescence, invasion, and ultracentrifugal assays.', 'Salvicine significantly reduced the lung metastatic foci of MDA-MB-435 orthotopic xenograft, without affecting primary tumor growth obviously. A comparison of gene expression profiles of primary tumors and lung metastatic focus between salvicine-treated and untreated groups using the CLOTECH Atlas human Cancer 1.2 cDNA microarray revealed that genes involved in tumor metastasis, particularly those closely related to cell adhesion and motility, were obviously down-regulated, including fibronectin, integrin alpha3, integrin beta3, integrin beta5, FAK, paxillin, and RhoC. Furthermore, salvicine significantly down-regulated RhoC at both mRNA and protein levels, greatly inhibited stress fiber formation and invasiveness of MDA-MB-435 cells, and markedly blocked translocation of both RhoA and RhoC from cytosol to membrane.']

['To assess the relationship between congenital uterine malformations and blood pressure in pregnancy.', 'Twenty-four-hour automated ambulatory blood pressure monitoring (readings every 30 min) was performed in 16 normotensive, nonproteinuric, primigravidae with congenital uterine malformations (5 uterus septus, 9 uterus bicornis, 2 uterine didelphys) between 20 and 30 weeks. From the 24-hr blood pressure report, we calculated 24-hr mean, daytime and nighttime means. The results were compared with 16 primigravidae, matched for age and gestation, who were and remained normotensive throughout pregnancy, and tested for statistics with t-test; significance assessed at p < 0.001.', 'Although they were within the normotensive range, all blood pressure measurements considered were significantly higher in pregnant women with congenital uterine malformations, compared to normal pregnant women. Namely, 24-hr, daytime, and nighttime systolic (mean +/- SD) were 121.1 +/- 8.4, 124.4 +/- 8.8, 114.0 +/- 7.7 mmHg, respectively, in women with uterine malformations and 108.0 +/- 7.4, 109.2 +/- 7.3, 102.1 +/- 8.5 mmHg, respectively, in normal pregnant women. Twenty-four-hour diastolic, daytime, and nighttime diastolic (mean +/- SD) 74.1 +/- 10.2, 77.1 +/- 10.6, 68.1 +/- 9.2 mmHg, in women with uterine malformations and 64.1 +/- 5.7, 66.0 +/- 5.7, 58.2 +/- 6.3 mmHg, in normal pregnant women (all differences p < 0.001). Fifteen of the fetuses from women with congenital uterine malformations showed intrauterine growth retardation. No differences were found 6 months after delivery.']

['Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications. We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose (MCR) than conventional hypocaloric diet. The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes (T2D).', 'Subjects with T2D (n=74) were randomly assigned into a vegetarian group (VG, n=37) following vegetarian diet or a control group (CG, n=37) following a conventional diet. Both diets were calorie restricted (-500\u2009kcal\u2009day(-1)). Participants were examined at baseline, 12 weeks of diet intervention and 24 weeks (subsequent 12 weeks of diet were combined with aerobic exercise). The fatty acid composition of serum phospholipids was measured by gas liquid chromatography. MCR was measured by hyperinsulinemic isoglycemic clamp. Visceral fat (VF) was measured by magnetic resonance imaging.', 'Linoleic acid (LA; 18:2n6) increased in VG (P=0.04), whereas it decreased in CG (P=0.04) in response to dietary interventions. It did not change significantly after the addition of exercise in either group (group × time P<0.001). In VG, changes in 18:2n6 correlated positively with changes in MCR (r=+0.22; P=0.04) and negatively with changes in VF (r=-0.43; P=0.01). After adjustment for changes in body mass index, the association between 18:2n6 and MCR was no longer significant. The addition of exercise resulted in greater changes of phospholipid fatty acids composition in VG than in CG.']

['This study aims to investigate the effect of 5(S), 6(R)-7-trihydroxymethyl heptanoate (BML-111) on the Wnt5a/frizzled-5 (FZD5)/calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathway in septic mice, and to explore whether this pathway mediates the effect of BML-111 on inflammatory response in lipopolysaccharide (LPS)-induced RAW 264.7 cells.', 'The cecal ligation and puncture-induced mouse model of sepsis was constructed, and the mice were pretreated with BML-111. In vitro, LPS-induced RAW 264.7 cells were incubated with various concentrations of BML-111. Activation of Wnt5a/FZD5/CaMKII signaling pathway was achieved by transfection of the Wnt5a overexpression plasmid. The levels of interleukin-1 beta (IL-1β), IL-6 and IL-8 in the mouse serum and cell supernatant were determined by ELISA assay. The expression of Wnt5a, FZD5 and CaMKIIδ was examined by western blot analysis.', 'The results from the in vivo studies revealed that BML-111 shows inhibitory effect on IL-1β, IL-6 and IL-8 expression in the serum of septic mice, and suppresses the expression of Wnt5a, FZD5 and CaMKIIδ protein. The in vitro studies demonstrated that BML-111 inhibits Wnt5a, FZD5 and CaMKIIδ proteins in a dose-dependent manner. BML-111 suppressed the levels of IL-1β, IL-6 and IL-8 in LPS-induced RAW 264.7 cells; however, this effect could be attenuated by transfection of the Wnt5a overexpression plasmid.']

['Ultrapure alginate gel is promising in terms of adhesion prevention. Because anti-adhesive barriers have been shown to disturb healing of bowel anastomoses, the effect of ultrapure alginate gel on the repair of colon anastomoses was studied.', 'In 102 male Wistar rats, a 0.5-cm segment was resected from the descending colon and continuity was restored by an inverted single-layer end-to-end anastomosis. Animals were randomized into a control, an alginate gel, and a sodium hyaluronate carboxymethyl cellulose film group, each n\xa0=\xa034. Half of each group was sacrificed at day 3 and 7 postoperatively. Anastomotic strength was assessed by measuring both bursting pressure and breaking strength. Hydroxyproline content was measured and histologic analysis was performed. The incidence of adhesion and abscess formation was scored at sacrifice.', 'No difference in either anastomotic-bursting pressure or breaking strength was found between experimental groups and the controls at any time point. Both the incidence of adhesion formation (35% versus 71%, P\xa0=\xa00.007) and the adhesion score (0.38 versus 0.79, P\xa0=\xa00.009) were significantly lower in the alginate gel group than in the controls. The abscess rate was higher (46% versus 18%, P\xa0=\xa00.030) in the hyaluronate carboxymethyl cellulose group than in the controls and unchanged in the alginate gel group.']

['Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL) nerve is an ideal model system for live studies of axon degeneration and regeneration.', 'We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths.']

['Cochlear implant users still experience severe limitations regarding sound quality, music appreciation, and speech perception in adverse listening situation. To improve hearing in noisy environments, the incorporation of signal enhancement algorithms was initiated.', 'The study group consisted of 13 postlingually deafened adults using HiRes 120. Participants were fitted with 2 versions of the noise reduction algorithm: a moderate and a strong setting. In an immediate session, the HSM sentence test in speech-shaped noise was administered using the clinical program as well as both noise reduction programs. Participants were asked to try all 3 programs in everyday listening situations at home and provide a rating of sound quality and speech perception via a questionnaire (Abbreviated Profile of Hearing Aid Benefit).', 'During the fitting, no difficulties were encountered, and all participants accepted the noise reduction programs without any acclimatization. All participants achieved better results with both noise reduction programs in the HSM sentence test in noise compared with the clinical program. Group mean speech perception scores were highly significantly better for the ClearVoice settings compared with the clinical program score. The majority preferred one of the ClearVoice conditions, with 4 participants for the strong and 3 for the moderate setting.']

['Hepatocellular carcinoma (HCC) is one of the deadliest solid cancers and is the third leading cause of cancer-related death. There is a universal estimated male/female ratio of 2.5, but the reason for this is not well understood. The Sleeping Beauty (SB) transposon system was used to elucidate candidate oncogenic drivers of HCC in a forward genetics screening approach. Sex bias occurrence was conserved in our model, with male experimental mice developing liver tumors at reduced latency and higher tumor penetrance. In parallel, we explored sex differences regarding genomic aberrations in 235 HCC patients. Liver cancer candidate genes were identified from both sexes and genotypes. Interestingly, transposon insertions in the epidermal growth factor receptor (Egfr) gene were common in SB-induced liver tumors from male mice (10/10, 100%) but infrequent in female mice (2/9, 22%). Human single-nucleotide polymorphism data confirmed that polysomy of chromosome 7, locus of EGFR, was more frequent in males (26/62, 41%) than females (2/27, 7%) (P = 0.001). Gene expression-based Poly7 subclass patients were predominantly male (9/9) compared with 67% males (55/82) in other HCC subclasses (P = 0.02), and this subclass was accompanied by EGFR overexpression (P < 0.001).']

['High SOCS3 expression in intestinal epithelial cells (IECs) of patients with ulcerative colitis (UC) in remission reflects the shorter time to relapse. We investigated whether high SOCS3 increased risk for relapse through violating STAT3-dependent protective effects of interleukin (IL)-22 during UC remission.', 'Expression of IL-22 and c-Myc in UC remission mucosa was analyzed by immunohistochemistry. Effects of IL-22 on migration and proliferation of IEC cell lines with enforced SOCS3 expression were assessed with wounding assay and CCK-8 assay, respectively. Influence of STAT3 interference and SOCS3 overexpression on IL-22-regulated expression of antimicrobial peptide and proliferation-related molecules, including DMBT1, c-Myc, Survivin, Bcl-2, and Bcl-xL, were performed with quantitative real-time polymerase chain reaction or Western blot.', 'Patients with UC in remission showed significantly more IL-22-positive immune cells, but no difference of epithelial c-Myc levels, in mucosa compared with healthy controls. Overexpression of SOCS3 nearly abolished IL-22-induced activation of STAT3. By inhibiting STAT3 signaling, SOCS3 influenced IL-22-induced expression of DMBT1, c-Myc, Survivin, and Bcl-2 as well as proliferation and migration processes in cultured IEC cell line.']

['Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. In order to examine whether the allele distribution of the single nucleotide polymorphism (SNP) in gene STAT4 rs7574865 in patients with SLE is different from those of healthy controls in Chinese Northern Han population, we investigated whether the variants of STAT4 rs7574865 were associated with any specific clinical features of SLE.', 'We genotyped SNPs in STAT4 rs7574865 in 252 patients with SLE and 497 healthy controls. All subjects were from the Northern part of Chinese Han population. The genotypes in rs7574865 were determined by polymerase chain reaction (PCR) and consequence direct sequencing of PCR products in the DNA samples.', 'There was a significant difference in distribution of the SNPs in rs7574865 between the SLE patients and healthy controls. Compared with healthy controls, there was a significant correlation between TT genotypes in rs7574865 and the risk of SLE when GG genotype was used as a reference genotype after adjusting for gender and age. The frequency of T allele in the SLE patients was strongly significantly higher than that of healthy controls. Furthermore, there was a significant difference in the distribution of SNP in rs7574865 between male and female SLE patients, when compared with healthy controls. The frequency of T allele in rs7574865 in male patients was significantly higher than that of male healthy controls or female patients. There was no significant correlation between the frequencies of T allele in STAT4 rs7574865 and the clinical features of SLE.']

['The lung is critical in surveillance and initial defense against pathogens. In humans, as in mice, individual genetic differences strongly modulate pulmonary responses to infectious agents, severity of lung disease, and potential allergic reactions. In a first step towards understanding genetic predisposition and pulmonary molecular networks that underlie individual differences in disease vulnerability, we performed a global analysis of normative lung gene expression levels in inbred mouse strains and a large family of BXD strains that are widely used for systems genetics. Our goal is to provide a key community resource on the genetics of the normative lung transcriptome that can serve as a foundation for experimental analysis and allow predicting genetic predisposition and response to pathogens, allergens, and xenobiotics.', 'Steady-state polyA+ mRNA levels were assayed across a diverse and fully genotyped panel of 57 isogenic strains using the Affymetrix M430 2.0 array. Correlations of expression levels between genes were determined. Global expression QTL (eQTL) analysis and network covariance analysis was performed using tools and resources in GeneNetwork http://www.genenetwork.org.', 'Expression values were highly variable across strains and in many cases exhibited a high heritability factor. Several genes which showed a restricted expression to lung tissue were identified. Using correlations between gene expression values across all strains, we defined and extended memberships of several important molecular networks in the lung. Furthermore, we were able to extract signatures of immune cell subpopulations and characterize co-variation and shared genetic modulation. Known QTL regions for respiratory infection susceptibility were investigated and several cis-eQTL genes were identified. Numerous cis- and trans-regulated transcripts and chromosomal intervals with strong regulatory activity were mapped. The Cyp1a1 P450 transcript had a strong trans-acting eQTL (LOD 11.8) on Chr 12 at 36 ± 1 Mb. This interval contains the transcription factor Ahr that has a critical mis-sense allele in the DBA/2J haplotype and evidently modulates transcriptional activation by AhR.']

['Chronic stroke survivors with low hip bone density are particularly prone to fractures. This study shows that fear of falling is independently associated with falls in this population. Thus, fear of falling should not be overlooked in the prevention of fragility fractures in these patients.', 'Chronic stroke survivors with low bone mineral density (BMD) are particularly prone to fragility fractures. The purpose of this study was to identify the determinants of balance, mobility and falls in this sub-group of stroke patients.', 'Thirty-nine chronic stroke survivors with low hip BMD (T-score <-1.0) were studied. Each subject was evaluated for the following: balance, mobility, leg muscle strength, spasticity, and fall-related self-efficacy. Any falls in the past 12 months were also recorded. Multiple regression analysis was used to identify the determinants of balance and mobility performance, whereas logistic regression was used to identify the determinants of falls.', 'Multiple regression analysis revealed that after adjusting for basic demographics, fall-related self-efficacy remained independently associated with balance/mobility performance (R2 = 0.494, P < 0.001). Logistic regression showed that fall-related self-efficacy, but not balance and mobility performance, was a significant determinant of falls (odds ratio: 0.18, P = 0.04).']

['To examine the influence of cloudy media on the slow double-stimulation multifocal electroretinogram (mfERG).', 'Slow double-stimulation mfERG responses were measured from 26 subjects with normal ocular health under normal and light scattering conditions (induced using acrylic sheets) (Experiment 1) and another nine cataract patients before and after cataract surgery (Experiment 2). The amplitudes and implicit times of the first (M(1)) and second (M(2)) stimulation were compared under normal and light scattering conditions in Experiment 1 and they were compared under precataract and postcataract surgery in Experiment 2.', 'Compared with control conditions (normal and postcataract surgery), the M(1) amplitude in the central region was significantly reduced in light scattering conditions (acrylic sheets and precataract surgery); the M(2) amplitude and both M(1) and M(2) implicit times of all regions examined were moderately affected in precataract surgery. The M(1):M(2) amplitude ratio and implicit time ratio were virtually unaffected in cloudy media for either central or mid-peripheral regions.']

['Both multiple injection and single posterior cord injection techniques are associated with extensive anesthesia of the upper limb after an infraclavicular coracoid block (ICB). The main objective of this study was to directly compare the efficacy of both techniques in terms of the rates of completely anesthetizing cutaneous nerves below the elbow.', 'Seventy patients undergoing surgery at or below the elbow were randomly assigned to receive an ICB after the elicitation of either a single radial nerve-type response (Radial group) or of two different main nerve-type responses of the upper limb, except for the radial nerve (Dual group). Forty milliliters of 1.5% mepivacaine was given in a single or a dual dose, according to group assignment. The sensory block was assessed in each of the cutaneous nerves at 10, 20 and 30 min. Block performance times and the rates of complete anesthesia below the elbow were also noted.', 'Higher rates of sensory block of the radial nerve were found in the Radial group at 10, 20 and 30 min (P<0.05). The rates of sensory block of the ulnar nerve at 30 min were 97% and 75% in the Radial and in the Dual groups, respectively (P<0.05). The rate of complete anesthesia below the elbow was also higher in the Radial group at 30 min (P<0.05).']

['The concern over rising antibiotic resistance necessitates exploration of alternative approaches in antimicrobial therapy. Bacterial communities use the auto-inducer 2 (AI-2) quorum sensing signal at a specific threshold level for intra- and interspecies communication in order to regulate virulence behaviour. AI-2 signal production occurs in bacteria that possess a luxS homologue. In this study, we investigate for the first time the association between AI-2 signalling and susceptibility to antibiotics.', 'Streptococcus anginosus wild-type and its isogenic luxS mutant SA001 were exposed to erythromycin and ampicillin. Susceptibility to erythromycin and ampicillin was determined by measuring the cell density and viability. Complementation assays were conducted by exposing the mutant to wild-type supernatant or to the AI-2 precursor molecule dihydroxy-2,3-pentanedione (DPD).', 'Disruption of luxS in S. anginosus resulted in a mutant with increased susceptibility to erythromycin and ampicillin. Supernatant from S. anginosus wild-type partially restored growth of SA001 in the presence of the two antibiotics. DPD restored growth of the luxS mutant in the presence of erythromycin and ampicillin to values similar to that of S. anginosus wild-type.']

['Candida species are major causes of invasive mycoses in immunocompetent and immunocompromised hosts. Treatment options are limited in the setting of antifungal resistance and increased rates of echinocandin-resistant Candida glabrata have been reported. The novel arylamidine T-2307 demonstrates potent in vitro antifungal activity against Candida species. Our objective was to evaluate the in vitro and in vivo activity of T-2307 against resistant C. glabrata.', 'In vitro activity was determined against 42 clinical C. glabrata isolates, including 17 echinocandin-resistant strains. Neutropenic ICR mice were inoculated intravenously with an echinocandin-resistant C. glabrata isolate (T-2307; caspofungin MICs ≤0.008 and 0.5 mg/L, respectively). Therapy with vehicle control, T-2307 (0.75, 1.5, 3 or 6 mg/kg subcutaneously once daily) or caspofungin (1 or 10 mg/kg intraperitoneally once daily) began 1 day post-challenge. Kidneys were collected on day 8 and fungal burden was assessed by counting cfu.', 'T-2307 demonstrated potent in vitro activity against C. glabrata (geometric mean MIC 0.0135 mg/L), which was maintained against echinocandin-resistant isolates (geometric mean MIC 0.0083 mg/L). T-2307 also demonstrated in vivo efficacy in mice infected with echinocandin-resistant C. glabrata. Significant reductions in fungal burden were observed at each dosage level of T-2307 compared with control. Reductions in fungal burden were also observed with high-dose caspofungin.']

['An abnormal glucose tolerance (AGT) in coronary artery disease (CAD) patients could negatively influence recovery after an acute event but the question, relevant in the field of cardiac rehabilitation (CR), is still controversial.', 'Prospective study, aiming to establish the prevalence of AGT and its possible influence on functional recovery in CAD patients without a previous diagnosis of diabetes mellitus (DM).', 'An oral glucose tolerance test was performed on 230 CAD patients without known DM, submitted to a 2-week period of intensive exercise-based CR after a recent acute myocardial infarction or coronary artery bypass graft. Functional capacity was assessed by a cardiopulmonary exercise test (CPET) and by 6-minute walking tests (6MWT) performed both on admission and at discharge.', 'The prevalence of AGT in our population was 53%. Exercise capacity was lower in AGT patients (maximum workload achieved at CPET 79.3\u2009±\u200929.9 vs. 91.8\u2009±\u200936.9 W, p\u2009=\u20090.01; peak-VO(2) 17.8\u2009±\u20094.7 vs. 19.8\u2009±\u20095.6\u2009ml/kg/min, p\u2009=\u20090.01). In the subgroup of AGT patients characterized by an inferior walking capacity at baseline, the increment in the distance walked was less than in the controls (Δ6MWT: 81.9\u2009±\u200960.1 vs. 109.1\u2009±\u200972.1, p\u2009=\u20090.04). An independent, negative, association was observed between AGT and Δ6MWT in patients with lower baseline test, and between maximum workload and peak-VO(2) in the whole population.']

['Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc) are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy.', 'Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29) and healthy controls (n = 29) using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters.', 'The absolute count of lymphocytes (P = 0.0042), CD3+ (P = 0.0014), CD4+ (P = 0.0070), CD8+ (P = 0.021), and CD19+ cells (P = 0.024) was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P=0.165; P = 0.632, respectively). There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement), except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020).']

['To determine if docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplementation influences growth or visual acuity of formula-fed premature infants.', 'Double-blind, multi-center study of 194 premature infants given preterm formula with no DHA or ARA (control), 0.15% energy DHA, or 0.14% DHA + 0.27% ARA from single-cell triglycerides for at least 28 days and then fed term formula (no DHA or ARA) to 57 weeks postmenstrual age (PMA), with 90 breast-fed term infants as reference.', 'Infants fed DHA+ARA formula gained weight significantly faster (post-hoc analysis) during preterm formula feeding than control infants (34.7 vs. 30.7 g/d) and had weights and weight:length ratios not different from term breast-fed infants at 48 and 57 weeks PMA. Infants fed control or DHA formula had lower body weights than term infants. Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40, 48, and 57 weeks PMA (r = 0.19 to 0.24, P =.004-.02). Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events.']

['Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased risk for stroke. Hyperuricemia is a common finding in NIDDM, but its significance as an independent risk factor for cardiovascular disease has remained uncertain. Therefore, we investigated serum urate as a predictor of stroke in NIDDM patients free of clinical nephropathy (ie, with a serum creatinine level of < or = 120 micromol/L).', 'In this population-based study, cardiovascular risk factors were determined in 1017 patients (551 men and 466 women) with NIDDM, aged 45 to 64 years at baseline. The patients were followed up for 7 years with respect to stroke events.', 'During the follow-up period, 31 NIDDM patients (12 men [2.2%] and 19 women [4.1%]) died from stroke and 114 NIDDM patients (55 men [10.0%] and 59 women [12.7%]) had a fatal or nonfatal stroke. The incidence of stroke increased significantly by quartiles of serum uric acid levels (P<.001). High uric acid level (above the median value of > 295 micromol/L) was significantly associated with the risk of fatal and nonfatal stroke by Cox regression analysis (hazard ratio, 1.93 [1.30 to 2.86]; P=.001). This association remained statistically significant even after adjustment for all cardiovascular risk factors (hazard ratio, 1.91 [1.24 to 2.94]; P=.003).']

['Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type\xa01 diabetes. This study compared the gut microbiota of patients with Type\xa01 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes.', 'Ten males with Type\xa01 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO', 'Faecalibacterium\xa0sp., Roseburia\xa0sp. and Bacteroides\xa0sp. were typically the most abundant members of the community in both patients with Type\xa01 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type\xa01 diabetes compared with controls. The functional profiles were more conserved and the Type\xa01 diabetes group were comparable with the control group.']

['women of non-English speaking background who migrate by choice or seek refuge in developed countries such as Australia have notably poorer perinatal outcomes than local-born women. Using data collected in two consecutive population-based surveys conducted in 2000 and 2008, the objective of this paper is to compare the views and experiences of immigrant women of non-English speaking background (NESB) giving birth in Victoria, Australia with those of women who were born in Australia.', 'consecutive population-based surveys of women giving birth in Victoria, Australia conducted in 2000 and 2008. Questionnaires were distributed to women giving birth in a two-week period in 2000 and a four-week period in 2008 by hospitals and home birth practitioners. Surveys were mailed to women at five to six months post partum.', 'completed surveys were received from 67% of eligible women in 2000 (1616/2412), and 51.2% in 2008 (2900/5667). Compared to Australian-born women, immigrant women of NESB were more likely to report negative experiences of antenatal, intrapartum and postnatal care. In 2008, 47.1% of immigrant women expressed dissatisfaction antenatal care compared with 26.8% of Australian born women (Adj OR 2.17, 95% CI 1.7-2.7). Similarly, 40.5% of immigrant women were dissatisfied with intrapartum care compared with 25.5% of Australian born women (Adj OR 1.81, 95% CI 1.4-2.3), and 53.5% of immigrant women rated their postnatal care negatively compared with 41.0% of Australian born women (Adj OR 1.52, 95% CI 1.2-1.9). There was no evidence of improvement between the two surveys. Immigrant women were more likely than Australian-born women to say that health professionals did not always remember them between visits, make an effort to get to know the issues that were important to them, keep them informed about what was happening during labour or take their wishes into account.']

['CT angiography spot sign predicts hematoma expansion in patients with acute intracerebral hemorrhage (ICH). The spot sign may represent a site of active extravasation, a locus of arrested hemorrhage forming fibrin globes, or represent associated epiphenomena such as hypertensive microaneurysms. We sought to describe the evolution of spot signs over 60 seconds in acute ICH using dynamic CT angiography and determine whether they grow and diffuse into the hematoma as would be expected with active extravasation.', 'We prospectively identified consecutive patients presenting with spontaneous ICH<6 hours from symptom onset that completed dynamic CT angiography imaging over a 60-second acquisition protocol. We determined spot positivity, quantified spot volumes, and then used repeated-measures ANOVA to assess changes in spot volume over time.', 'We collected data on 35 patients; 13 of 35 (37%) patients were spot-positive. Spot-positive patients had larger median ICH volume compared with spot-negative patients (median 10.7 versus 49.2 mL; P=0.007). Maximal spot sign volumes ranged from 0.02 to 2.8 mL (median 0.17 mL). Spot sign volumes increased significantly with time (P<0.001) and seemed to disperse into the hematoma in all cases. Three of 13 (23%) spot-positive patients presented with 2 distinct spot signs, but the remaining patients either had only 1 spot sign or different contiguous components of an irregularly shaped spot sign.']

['The aim of this study was to investigate the linkage among ambulance transports, the number of death and air temperature in Takamatsu area, Japan.', 'Monthly data of ambulance transports (total and acute disease) and the number of death from 2004 to 2012 were obtained from Fire Department Service in Takamatsu and Takamatsu city official website, Japan. Climate parameters for required period were also obtained from Japan Meteorological Agency. Population data in Takamatsu area were also used to adjust ambulance transports and the number of death. The linkage among ambulance transports, the number of death and climate parameters was evaluated by ecological analysis.', 'Total ambulance transports (/a hundred thousand people/day) and ambulance transports due to acute disease (/a hundred thousand people/day) were 12.3 ± 0.9 and 6.8 ± 0.7, respectively. The number of death (/a hundred thousand people/day) was 2.5 ± 0.4. By quadratic curve, ambulance transports due to acute disease and the number of death were significantly correlated with the parameters of air temperature. However, the number of death was the highest in January and the lowest in August.']

['Diurnal preference towards eveningness among adults has been associated with unhealthy habits and a range of health hazards, such as sleeping problems and higher odds for depression. We wanted to analyse whether diurnal preference towards eveningness is associated with more severe symptoms regarding sleep problems and mental disorders among young adults.', 'Our sample consists of 469 young adults, aged 18-29 years, from the Mental Health in Early Adulthood Study in Finland (MEAF) conducted in 2003-2005. Chronotype was based on the assessment of one question that was asked first in 2000-2001 and the second time in 2003-2005. Those 73 participants who changed their chronotype were excluded from the main analysis, but separate analyses were performed with this group.', 'Concerning sleep, E-types reported higher dependency on alarm clocks (p < 0.001), and E-types and I-types had more problems in feeling refreshed after waking up (p < 0.0001 and p < 0.05 respectively) than M-types. Regarding mental health, E-types and I-types had lower odds for any lifetime DSM-IV Axis I disorder (p < 0.05 and p < 0.01 respectively) than M-types.']

['Sonographic measurement of the inferior vena cava (IVC) caval index predicts central venous pressure in ED patients. Fluid responsiveness (FR) is a measure of preload dependence defined as an increase in cardiac output secondary to volume expansion. We sought to determine if the caval index is an accurate measurement of FR in ED patients.', 'We conducted a prospective, observational trial at an urban, academic, adult ED with an annual census >105\u2009000. Included patients were clinically suspected of eu- and hypovolemia. Excluded patients were <18 years old, pregnant, incarcerated, sustained significant trauma or unable to consent. Supine IVC diameter was measured by bedside ultrasonography (M-Turbo; Sonosite, Bothwell, WA, USA). Caval index\u2009=\u2009[(expiratory IVC diameter\u2009-\u2009inspiratory IVC diameter)/expiratory IVC diameter]\u2009×\u2009100. FR was defined as an increase in the cardiac index by >10% by impedance cardiography (BioZ; Sonosite) following passive leg raise. The primary outcome was analysed using Spearman correlations for non-parametric data and the area under the receiver operating characteristics curve by Wilcoxon method.', 'Thirty patients were enrolled; four were excluded because of incomplete data collection. Thirty-one per cent (95% CI 13-48) of the patients were FR. The mean initial caval and cardiac index were 15.8% (95% CI 9.5-22) and 2.9\u2009L/min/m(2) (95% CI 2.6-3.2), respectively. Caval index did not predict FR (receiver operating curve\u2009=\u20090.46, 95% CI 0.21-0.71, P\u2009=\u20090.63).']

['Because of their regenerative and paracrine abilities, cardiac stem cells (CSCs) are the most appropriate, optimal and promising candidates for the development of cardiac regenerative medicine strategies. However, native and exogenous CSCs in ischemic hearts are exposed to various pro-apoptotic or cytotoxic factors preventing their regenerative and paracrine abilities.', 'We examined the effects of H2O2 on mouse CSCs (mCSCs), and observed that hydrogen peroxide (H2O2) treatment induces mCSCs apoptosis via the caspase 3 pathway, in a dose-dependent manner. We then examined the effects of Wnt1 over-expression on H2O2-induced apoptosis in mCSCs and observed that Wnt1 significantly decreased H2O2-induced apoptosis in mCSCs. On the other hand, inhibition of the canonical Wnt pathway by the secreted frizzled related protein 2 (SFRP2) or knockdown of β-catenin in mCSCs reduced cells resistance to H2O2-induced apoptosis, suggesting that Wnt1 predominantly prevents H2O2-induced apoptosis through the canonical Wnt pathway.']

['To directly examine the contribution of vitamin C to the antioxidant potential of fruits and vegetables, the antioxidant effect of orange juice consumption (8 and 16 fl. oz.) was compared to the antioxidant effect of supplemental vitamin C (dosage equivalent to that supplied by 8 fl. oz. of orange juice).', 'Subjects (n = 11; 28.6 +/- 2.1 years) received each treatment in a 3 x 3 randomized crossover design, and each two-week treatment was preceded by a two-week washout. During the entire trial, subjects restricted fruit and vegetable consumption to < or =3 servings per day except the vitamin C-rich foods (items containing >20 mg/serving), which were restricted to < or =3 servings per week. A fasting blood sample was collected at the end of each washout and each treatment period.', 'Following washouts, plasma vitamin C and lipid peroxidation (plasma TBARS) were similar by treatment group and averaged 25.4 +/- 3.6 micromol/L and 3.82 +/- 0.10 nmol/mL respectively. Plasma vitamin C concentrations were similar following each treatment period, 37.9 +/- 8.1, 45.8 +/- 9.4, and 38.3 +/- 12.4 micromol/L for the 8 and 16 fl. oz. orange juice treatments and the supplement treatment, respectively. All intervention treatments reduced plasma TBARS as compared to pretreatment values: -47% (p = 0.013), -40% (p = 0.083), and -46% (p = 0.015) for the 8 and 16 fl. oz. orange juice treatments and supplement treatment respectively.']

['Micro ribonucleic acid (miR-101) can regulate the expression of cyclooxygenase-2 (COX-2) and participate in the pathogenesis of malignant tumors. This study investigates the effects of miRNA-101 and COX-2 in lung cancer and the impact of miR-101 on the proliferation and invasion of human lung cancer A549 cell line.', 'The expression of miR-101 in 20 separate lung cancer tissues was detected by real time polymerase chain reaction; COX-2 expression was also detected. A549 cells were transfected with miR-101 or negative control oligonucleotide duplex mimic (miR-NC). In vivo tumorigenesis abilities were detected in localized human lung cancer xeno-transplant models in BALB/c nude mice.', 'MiR-101 expression was significantly lower and the level of COX-2 significantly higher in lung cancer tissues than in adjacent parenchyma (2.918 ± 1.006 vs. 5.953 ± 1.976, P = 0.001; 0.887 ± 0.260 vs. 0.355 ± 0.156, P = 0.001, respectively). Correlation analysis revealed that miR-101 negatively correlated with COX-2 in lung cancer tissues (R = -0.596, P = 0.002). Compared with A549-miR-NC cells, the expression of COX-2 was significantly decreased in A549 cells transfected with miR-101 (P < 0.001). The proliferation of A549 cells was markedly inhibited after transfection of miR-101. The in vivo tumor growth of A549 cells transfected with miR-101 was significantly slower than wide type A549 cells.']

['This study assessed the disparity in nutritional status of adolescents between public and private schools in urban Gambia.', 'This is a school-based cross-sectional study in six private and six public upper basic schools in urban Gambia. This study recruited 491 students from public and 469 students from private schools (13-15\xa0years of age).', "The prevalence of stunting (WHO height-for-age Z\xa0<\xa0-2SD) was 13.4\xa0% for public school students and 4.5\xa0% for private schools. After adjustment for children's sex, age, and family socioeconomic status, the differences in prevalence of stunting and underweight were significant between public and private schools. Private school students are more likely to be overweight/obese (WHO BMI-for-age Z\xa0>\xa0+1SD) (OR\xa0=\xa02.85, 95\xa0% CI 1.55-5.22), but less likely to be thin (BMI-for-age Z\xa0<\xa0-2SD) (OR\xa0=\xa00.61 [0.39-0.96]), compared to public school students. Children from lower income families had lower odds for overweight/obese than normal weight, compared to those from higher income families (OR\xa0=\xa00.34 [0.15-0.76])."]

['Survivin was aberrantly expressed in most cancer tissues, suggesting that survivin plays an important role in carcinogenesis. This study was designed to investigate the function and mechanism of survivin mutants in tumor cells.', 'The site-mutant and truncated survivin mutants were transfected into HeLa cells and selected using G418. Cell apoptosis was analyzed using flow cytometry. Protein level of cyclin D1 was detected by Western blot analysis.', 'Survivin mutant plasmid expressed in the HeLa cells successfully. The expressed protein could be detected using related antibody. Colony formation ability significantly decreased in the HeLa cells with survivin mutants compared with that in the parental HeLa cells. The HeLa cells transfected instantly with survivin mutants could undergo apoptosis automatically. Meanwhile, survivin mutants could cause an increase of multinuclear HeLa cells. The effect of survivin-N showed more effective than that of survivin T34A. Survivin-N and survivin T34A could influence the expression of cyclin D1 and reduced its protein levels of 68% and 12%, respectively.']

['Venous filling time (VFT90) is the time taken to reach 90% of the venous volume in the calf. It is recorded by air-plethysmography (APG(®)) and is assumed to measure global venous reflux duration. However, this has never been confirmed by duplex. The aim of the study was to compare VFT on APG to venous reflux time/duration (RT) measured simultaneously with duplex on the same patients.', 'Twenty-six consecutive patients, M:F = 16:10, age (25-78), C1 = 1, C2 = 4, C3 = 8, C4a = 6, C4b = 4, C5 = 2, C6 = 1, underwent simultaneous APG with duplex. The venous filling index (VFI, mL/second), VFT90 (seconds), great saphenous vein (GSV) RT on duplex, averaged thigh GSV diameter and thigh length (length) between the APG sensor air-cuff and duplex transducer were recorded. The VFT100 was calculated by VFT90/0.9. The additional time taken to fill the thigh was achieved using the VFI, length and deep vein diameter (d), to determine the corrected reflux duration: CRD = VFT100 + (length × πd(2)/4 (1/VFI)).', 'Twenty-five patients are presented. One patient with very mild reflux (VFT90 = 55.9 seconds) had an indeterminate endpoint on duplex and was excluded. The median (range) VFI and GSV diameter was 4.9(1.3-15.5) mL/second and 7(4-17) mm, respectively. The VFT90 and VFT100 both correlated with RT on duplex (Spearman, P < 0.0005) at: r = 0.933, r(2) linear = 0.72 and r = 0.933, r(2) linear = 0.68, respectively. The median (interquartile range) filling time with VFT90 was less than the duplex RT at 24 (16.9) versus 28 (20) seconds respectively, P < 0.0005 (Wilcoxon). The median percentage underestimation improved from 24% to 16% and then 4% using the VFT90, VFT100 and CRD, respectively.']

['A population-based study of 1363 older women showed that the 24% who achieved high physical activity and dietary calcium intakes had a 5.1% higher hip BMD than those who did not, supporting the concept that lifestyle factors play an important role in the maintenance of lower extremity bone mass in older women.', 'Although there is general agreement that increased dietary calcium consumption and exercise can slow bone loss in older women, the amount required to have this effect in an older population remains uncertain. This study was devised to examine the effects of calcium consumption (CC) and physical activity (PA) (lifestyle management) on bone mass in an older female population.', 'Using a cross-sectional study design, a population-based sample of older women (mean age, 75 +/- 3 years) had hip and heel bone mass measured using DXA (Hologic 4500A; n = 1076) and quantitative ultrasound (QUS, Lunar Achilles; n = 1363), respectively. CC and PA were measured by a validated habitual food frequency and activity questionnaire, respectively. Dose-response effects of PA and CC on bone mass were examined using ANOVA.']

['It is known that in vivo kinematics after total knee replacement is influenced by the design of the implant. The goal of this study was to show that the sagittal curvature of two different knee prostheses differing in geometric design predicts their in vivo motion behavior.', 'Three-dimensional tibio-femoral displacements of two prosthesis designs (single radius vs. dual radius) were measured during knee extension under weight bearing conditions by in vivo video fluoroscopy. Finite helical axes were computed to represent the tibio-femoral motions. Angular deviation alpha and the spatial localization deviation delta were used to characterize the motions. Angular deviation is the angle between each incremental finite helical axis and the medio-lateral axis of the femoral component of the prosthesis. The spatial localization deviation is the distance between each finite helical axis and the center of the femoral component of the prosthesis. Statistical comparisons were performed using the median and the interquartile range of the angular deviation and the spatial localization deviation.', 'The single-radius design showed finite helical axes concentrated at a single axis near to the medio-lateral axis of the femoral component. The angular and spatial localization deviation of the dual radius design were larger compared to the single radius design, exhibiting finite helical axes varying between two axes.']

['Whether connexin43 gap junctions (Cx43 GJs) and spatial heterogeneity of conduction velocity (CV) restitutions are altered in hearts during moderate (MH; 33°C) and severe (SH; 30°C) hypothermia remains unclear.', 'Using an optical mapping system, ventricular CV was evaluated by S₁ pacing in 29 Langendorff-perfused isolated rabbit hearts at baseline (37°C, n=9), 30-min MH (n=6), 30-min SH (n=9), and rewarming (R, 30-min SH followed by 30-min 37°C, n=5). After CV evaluation, myocardium was collected to measure the level and distribution of non-phosphorylated (NP-Cx43) and total (T-Cx43) Cx43 by immunoblotting and immunoconfocal microscopy. In 6 additional hearts, Cx43 GJ remodeling was evaluated at 30-min SH with (n=3) or without (n=3) pretreatment of a protein kinase C (PKC) inhibitor. CV slowing and spatial heterogeneities of CV restitutions were enhanced in MH and SH hearts. NP-Cx43 was downregulated in MH (P=0.002) and SH (P<0.001) hearts. NP-Cx43 levels among 4 different ventricular sites became inhomogeneous in MH (P=0.017) and SH (P=0.046) hearts. However, T-Cx43 levels were unchanged. The percentages of lateralized NP- and T-Cx43 were increased in MH, SH, and R hearts. Pretreatment of PKC inhibitor attenuated SH-induced NP-Cx43 lateralization (P=0.0495).']

["The rates of lumbar spinal fusion operations have increased dramatically over the past 2 decades, and several studies based on administrative databases such as the Nationwide Inpatient Sample (NIS) have suggested that the greatest rise is in the general categories of degenerative disc disease and disc herniation, neither of which is a well-accepted indication for lumbar fusion. The administrative databases classify cases with the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The ICD-9-CM discharge codes are not generated by surgeons but rather are assigned by trained hospital medical coders. It is unclear how accurately they capture the surgeon's indication for fusion. The authors sought to compare the ICD-9-CM code(s) assigned by the medical coder to the surgeon's indication based on a review of the medical chart.", "A retrospective review was undertaken of all lumbar fusions performed at our institution by the department of neurosurgery between 8/1/2011 and 8/31/2013. Based on the authors' review, the indication for fusion for each case was categorized as spondylolisthesis, deformity, tumor, infection, nonpathological fracture, pseudarthrosis, adjacent-level degeneration, stenosis, degenerative disc pathology, or disc herniation. These surgeon diagnoses were compared with the primary ICD-9-CM codes that were submitted to administrative databases.", "There were 178 lumbar fusion operations performed for 170 hospital admissions. There were 44 hospitalizations in which fusion was performed for tumor, infection, or nonpathological fracture; the remaining 126 were for degenerative diagnoses. For these degenerative cases, the primary ICD-9-CM diagnosis matched the surgeon's diagnosis in only 61 of 126 degenerative cases (48.4%). When both the primary and all secondary ICD-9-CM diagnoses were considered, the indication for fusion was identified in 100 of 126 cases (79.4%)."]

['Excess weight and type 2 diabetes lead to increased susceptibility to infections. Our aim was to investigate the role of diabetes-induced decreased arginine (Arg) availability and of a possible dysregulation of Arg metabolism in macrophages favoring inflammation and dysimmunity via altered nitric oxide (NO) and cytokine productions.', 'Isolated peritoneal macrophages from Zucker Diabetic Fatty (ZDF) or lean rats were incubated with increasing Arg concentration (0-2\xa0mM) and Arg metabolism and regulatory properties were studied.', 'Inducible NO synthase (iNOS) expression did not vary with Arg concentration while NO production reached a maximum at 0.5\xa0mM Arg, being significantly lower in macrophages from ZDF rats. Arginase I and II protein levels reached a maximum between 0.25 and 0.5\xa0mM Arg in controls; in macrophages from ZDF rats arginase I was significantly lower and progressively increased up to 2\xa0mM Arg while arginase II was not affected by Arg concentration. In parallel, Arg downregulated TNFα production in both groups and IL-6 only in control.']

['Indehiscent sporangia are reported for only a few of derived leptosporangiate ferns. Their evolution has been likely caused by conditions in which promotion of self-fertilization is an evolutionary advantageous strategy such as the colonization of isolated regions and responds to stressful habitat conditions. The Lepisorus clathratus complex provides the opportunity to test this hypothesis because these derived ferns include specimens with regular dehiscent and irregular indehiscent sporangia. The latter occurs preferably in well-defined regions in the Himalaya. Previous studies have shown evidence for multiple origins of indehiscent sporangia and the persistence of populations with indehiscent sporangia at extreme altitudinal ranges of the Qinghai-Tibetan Plateau (QTP).', 'Independent phylogenetic relationships reconstructed using DNA sequences of the uniparentally inherited chloroplast genome and two low-copy nuclear genes confirmed the hypothesis of multiple origins of indehiscent sporangia and the restriction of particular haplotypes to indehiscent sporangia populations in the Lhasa and Nyingchi regions of the QTP. In contrast, the Hengduan Mountains were characterized by high haplotype diversity and the occurrence of accessions with and without indehiscent sporangia. Evidence was found for polyploidy and reticulate evolution in this complex. The putative case of chloroplast capture in the Nyingchi populations provided further evidence for the promotion of isolated but persistent populations by indehiscent sporangia.']

['CD133 is one of the most important cancer-initiating (stem) cell markers and was confirmed to be expressed in solid cancers such as colon cancer. However, no one has investigated the role of CD133 in intrahepatic cholangiocarcinoma (IHCC). The aim of this study was to clarify the clinical role of CD133 expression in IHCC.', "Twenty-nine patients with IHCC who underwent hepatic resection at our institution were enrolled in this study. Expression of CD133 was examined using anti-CD133 antibody. Staining was observed in the cytoplasm of cancer cells and CD133-positive cells distributed in the whole tumor. The patients were divided into two groups: the CD133-positive group (n = 14) and CD133-negative group (n = 15), in which no staining of CD133 was observed. Clinicopathological factors including hypoxia-inducible factor-1alpha expression were compared between the two groups. The prognostic factors were investigated by multivariate analysis using Cox's proportional hazard model.", 'The 5-year survival rate in the CD133-positive group (8.0%) was worse than that in the CD133-negative group (57.0%). In the CD133-positive group, the incidence of intrahepatic metastasis and positive expression of hypoxia-inducible factor-1alpha tended to be higher than that in the CD133 negative group. The multivariate analysis revealed CD133 expression was an independent prognostic indicator in IHCC.']

['This study investigated whether inducing central sensitization evokes segmental increases in trigger point pressure sensitivity. We evoked central sensitization at the C(5) segment and validated its presence via mechanical cutaneous sensitivity (brush allodynia) testing. Trigger point pressure sensitivity was quantified using the pain pressure threshold (PPT) value. A 50 cm(2) area of the C(5) dermatome at the right lateral elbow was pretreated with 45 degrees heat for 10 minutes. Test subjects (n = 20) then received topical capsaicin cream (0.075%; Medicis, Toronto, Canada) to the C(5) dermatome, whereas control subjects (n = 20) received a topical placebo cream (Biotherm Massage, Montreal, Canada). PPT readings were recorded from the infraspinatus (C(5,6)) and gluteus medius (L(4,5)S(1)) trigger points at zero (pre-intervention), 10, 20, and 30 minutes after intervention; all PPT readings were normalized to pre-intervention (baseline) values. The difference between the PPT readings at the 2 trigger point sites represents the direct influence of segmental mechanisms on the trigger point sensitivity at the infraspinatus site (PPT(seg)). Test subjects demonstrated statistically significant increases in Total Allodynia scores and significant decreases in PPT(seg) at 10, 20, and 30 minutes after application, when compared with control subjects. These results demonstrate that increases in central sensitization evoke increases in trigger point pressure sensitivity in segmentally related muscles.']

['Chemical intolerance (CI) is characterised by negative health effects attributed to a heightened responsiveness to common airborne chemicals. This longitudinal study explored the hypothesised role of negative affect in the development and persistence of CI in a general population.', 'A general population sample aged 19 to 72 years was examined in 2006-2008 and again in 2011-2012. Longitudinal data on CI were analysed with the purpose of examining baseline negative affect as a risk factor for having developed CI at 5-year follow-up and for reporting persistent CI. Participants were classified as reporting no signs of CI, having symptoms of CI and as being a likely CI case based on self-reported reactions to 11 common chemical exposures, symptoms related to chemical exposures and daily life adjustments attributed to reactions when exposed to chemicals.', 'A total of 69.4% of the participants who had reported CI at baseline also reported CI at follow-up. In participants with no baseline CI, 15.5% reported CI at follow-up and 18.1% reported symptoms related to chemicals but no daily life adjustments. Baseline negative affect was positively and statistically significantly associated with both development and persistence of CI.']

["Altered extracellular matrix (ECM) remodeling and podocyte apoptosis are characteristic features of diabetic nephropathy (DN). Aliskiren (ALI) inhibits the renin-catalyzed conversion of angiotensinogen to angiotensin I. This study tested ALI's effect on podocyte ECM accretion and survival in a high-glucose environment in vitro.", 'Conditionally immortalized mouse podocytes were incubated in normal glucose (NG; 5.5 mM) or high glucose (HG; 40 mM) for 24-48 h with and without ALI (20 nM). Real-time RT-PCR was performed for fibronectin (FN), collagen α5(type IV) (Cola5IV), matrix metalloproteinases 2 and 9 (MMP2 and MMP9), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP1 and TIMP2). Western blots were performed for FN, Cola5IV, MMP2, MMP9, TIMP1 and cleaved (activated) caspase-3.', 'ALI significantly reduced the mRNA and protein levels of FN, Cola5IV and TIMP1, and the mRNA of TIMP2 and cleaved caspase-3. ALI had no effect on MMP2 mRNA or protein or MMP9 mRNA tested under HG conditions. Under NG conditions, ALI had no effect on FN, Cola5IV, MMP2, MMP9 and activated caspase-3 proteins. ALI decreased the activated caspase-3 protein and evidence of apoptosis by TUNEL staining observed in podocytes cultured under HG conditions.']

['The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques).', '80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools.', 'Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5-fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system-related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients.']

['Human milk contains immune molecules involved in the protection of newborns against infections. We analyzed the concentration of Deleted in Malignant Brain Tumors 1 (DMBT1), a protein with functions in innate immunity, in breast milk.', 'DMBT1 was detected in breast milk by Western blotting and its concentration was quantified by ELISA in 95 breast milk samples collected from mothers of preterm and term neonates during the first four weeks after delivery. Possible effects of maternal or neonatal parameters were analyzed by different statistical tests.', 'The mean DMBT1 concentration (± standard error of the mean) in the tested milk samples was 2.48\u2009±\u20090.26\u2009μg/mL (range: 0.112\u2009μg/mL to 17.984\u2009μg/mL) and represented 0.0087% of the total protein content. The comparison between the newborns with infection and the newborns without infection revealed significantly higher DMBT1 concentrations in breast milk in the group with infection (6.72\u2009±\u20092.53\u2009μg/mL versus 2.20\u2009±\u20090.35\u2009μg/mL (P\u2009=\u20090.031)). Neither maternal nor neonatal parameters showed a correlation with the milk DMBT1 levels.']

['MMP2 and MMP9 are two gelatinolytic enzymes, which are key regulators of tumor invasion and metastasis. This study aimed to clarify the prognostic significance of MMP2 and MMP9 with particular regard to their transcript levels, enzymatic activities in renal cell carcinomas (RCCs).', 'Through cDNA array, the differential expression of the MMP superfamily was evaluated in RCC. Various properties of MMP2 and MMP9 were quantified, in 178 patients with RCC, based on the Heidelberg classification. Of these, 145 cases including 16 fresh-frozen cases were available for MMP2 and MMP9 transcript level evaluation. In addition, gelatinolytic activity was assessed by zymography in 16 other fresh-frozen samples from new RCC cases.', "MMP2, 9, 11, 14, and 16 were upregulated in the conventional RCC in comparison with the chromophobe RCC, whereas MMP1, 11 and 16 were pronounced in papillary RCC. MMP9 transcript levels were strongly associated with the MMP9 enzymatic activity (p=0.001), and therefore, with disease-free survival (p=0.001) and metastasis (p=0.011). Gelatinolytic activity of MMP9 by zymography was strongly associated with MMP9 mRNA expression, which was more intense in 'conventional' RCC than in 'chromophobe' RCC (p=0.001), irrespective of tumor grade or stage. MMP9 was proven to be a significant prognostic predictor by multi-variate survival analysis (p=0.0054). MMP2 enzymatic activity disappeared in spite of its constant transcript expression in RCC."]

['To ascertain if protective ventilation can attenuate the damaging postoperative pulmonary effects of cardiopulmonary bypass (increases in airway pressure, decreases in lung compliance, and increases in shunt).', 'Prospective, randomized clinical trial.', 'Single university hospital.', 'Twenty-five patients undergoing elective coronary artery bypass graft procedure and early extubation.', 'Thirteen patients received conventional mechanical ventilation (CV; respiratory rate, 8 breaths/min; tidal volume, 12 mL/kg; fraction of inspired oxygen [FIO2], 1.0; positive end-expiratory pressure [PEEP], +5), and 12 patients received protective mechanical ventilation (PV; respiratory rate, 16 breaths/min; tidal volume, 6 mL/kg; FIO2, 1.0; PEEP, +5). Perioperative anesthetic and surgical management were standardized. Various pulmonary parameters were determined twice perioperatively: 10 minutes after intubation and 60 minutes after arrival in the intensive care unit.', 'The mean postoperative increase in peak airway pressure in group CV was significantly larger than the mean postoperative increase in peak airway pressure in group PV (7.1 v 2.4 cm H2O; p < 0.001). Group CV experienced significant postoperative increases in plateau airway pressure (p = 0.007), but group PV did not (p = 0.644). The mean postoperative decrease in dynamic lung compliance in group CV was significantly larger than the mean postoperative decrease in dynamic lung compliance in group PV (14.9 v 5.5 mL/cm H2O; p = 0.002). Group CV experienced significant postoperative decreases in static lung compliance (p = 0.014), but group PV did not (p = 0.645). Group CV experienced significant postoperative increases in shunt (15.5% to 21.4%; p = 0.021), but group PV did not (18.4% to 21.2%; p = 0.265).']

['Complex metacarpophalangeal (MCP) dislocations require open surgical reduction, but surgeons disagree about the best surgical approach. We hypothesized that a dorsal approach would require less operative time than would a volar approach and result in a decreased need for a secondary approach.', 'We performed a retrospective chart review of all isolated irreducible dorsal MCP dislocations treated at 2 level 1 trauma centers between 2005 and 2015. We recorded the initial surgical approach (volar or dorsal), total operative time, and whether the surgeon used a second surgical approach. Operative times for initial volar approach versus initial dorsal approach, hand surgeon versus non-hand surgeon, and thumb versus other digits were compared using the 2-tailed Student t test. We used Fisher exact test to compare the need for a second approach between the volar and dorsal approach groups.', 'A total of 21 patients (22 digits) with MCP dislocations required surgical reduction. Average operative time was longer for the 14 patients who underwent the initial volar approach (70 minutes) than for the 7 who underwent an initial dorsal approach (45 minutes). Six of the 14\xa0MCP joints approached volarly (42%) required a second dorsal approach. None of the 7\xa0patients in the dorsal group required a second approach.']

['Multiple sclerosis (MS) causes significant neurological disability. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Human bone marrow mesenchymal stem cells (hMSCs) possess anti-inflammatory and immunosuppressive effects. We studied whether hMSCs affect CD1d(high)CD5(+) regulatory B-cell activity in EAE.', 'EAE was induced in C57BL/6N mice by immunization with MOG35-55 peptide. hMSCs were injected intravenously into EAE mice on day 3 and day 12 after first immunization. Mice were sacrificed on day 26. Immunohistochemistry of the spinal cord, serum cytokines levels, production of cytokines by cultured splenic cells, and flow cytometry for splenic Th17 and CD1d(high)CD5(+) regulatory B cells were studied.', 'EAE mice with hMSC treatment on day 3 and day 12 had reduced EAE scores from day 14 to day 26 compared to EAE mice without hMSC treatment, and reduced infiltration of inflammatory cells and demyelination in the spinal cord. EAE mice with hMSC treatment on day 3 and day 12 had: (1) lower serum levels of IL-6, TNF-α (p < 0.0005), and IL-17 (p < 0.005 for day 3, p < 0.0005 for day 12); (2) reduced splenic cell production and secretion of IL-6, TNF-α (p < 0.05), and IL-17 (p < 0.05), and increased splenic production of IL-10; (3) reduced splenic Th17 cells (p < 0.05 for day 3, p < 0.005 for day 12), and (4) increased CD1d(high)CD5(+) regulatory B cells (p < 0.005) compared to EAE mice without hMSC treatment.']

["The purpose of this study was to examine the heart rate reserve (HRR) at first and second ventilatory thresholds (VT's) in postmenopausal women and compare it with optimal intensity range recommended by the ACSM (40-84%HRR). An additional aim was to evaluate whether a higher aerobic power level corresponded to a higher HRR at VT's.", "Fifty-eight postmenopausal women participated in this study (aged 48-69). A graded 25 Wmin(-2) cycle ergometer (Monark E839) exercise protocol was performed in order to assess aerobic power. The heart rate and gas-exchange variables were measured continuously using a portable gas analyzer system (Cosmed K4b). The first (VT1) and the second (VT2) VT's were determined by the time course curves of ventilation and O2 and CO2 ventilatory equivalents. A K-means clustering analysis was used in order to identify VO2max groups (cut-off of 30.5 mlkg(-1)min(-1)) and differences were evaluated by an independent sample t-test. Bland-Altman plots were performed to illustrate the agreement between methods.", "The women's HRR values at VT1 were similar to 40% HRR in both VO2max groups. At VT2 both VO2max groups exhibited negative differences (P<0.01) for the predicted 84%HRR intensity (-14.46% in the lower VO2max group and -16.32% in the higher VO2max group)."]

['Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis.', 'Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD.', 'From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation.']

['Established prognostic factors are of limited value to predict long-term survival and benefit from metastasectomy in advanced melanoma. This study aimed to identify prognostic factors in patients with distant metastasis.', 'We analysed overall survival of 855 institutional melanoma patients with distant metastasis by bivariate Kaplan-Meier survival probabilities and multivariate Cox hazard regression analysis.', 'Serum lactate dehydrogenases (LDH), S100B, the interval between initial diagnosis and occurrence of distant metastasis, the site of distant metastases, and the number of involved distant sites were significant independent prognostic factors in both bivariate and multivariate analyses. Visceral metastases other than lung (hazard ratio (HR) 1.8), elevated S100B (HR 1.7) and elevated LDH (HR 1.6) had the highest negative impact on survival. Complete metastasectomy was likewise an independent prognostic factor in multivariate analysis. This treatment was associated with favourable survival for patients with normal LDH and S100B values (5-year survival, 37.2%).']

['Survivin is known playing a role in drug resistance. However, its role in bortezomib-mediated inhibition of growth and induction of apoptosis is unclear. There are conflicting reports for the effect of bortezomib on survivin expression, which lacks of a plausible explanation.', 'In this study, we tested cancer cells with both p53 wild type and mutant/null background for the relationship of bortezomib resistance with survivin expression and p53 status using MTT assay, flow cytometry, DNA fragmentation, caspase activation, western blots and RNAi technology.', 'We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. However, silencing of survivin expression utilizing survivin mRNA-specific siRNA/shRNA in p53 mutant or null cells sensitized cancer cells to bortezomib mediated apoptosis induction, suggesting a role for survivin in bortezomib resistance. We further noted that modulation of survivin expression by bortezomib is dependent on p53 status but independent of cancer cell types. In cancer cells with mutated p53 or p53 null, bortezomib appears to induce survivin expression, while in cancer cells with wild type p53, bortezomib downregulates or shows no significant effect on survivin expression, which is dependent on the drug concentration, cell line and exposure time.']

['To investigate the role of the sympathetic nervous system in the cardiovascular response to quiet standing in the postprandial state.', 'Following a 30min pre-ingestion phase, 14 healthy young male subjects consumed a 600kcal carbohydrate-rich meal. Arterial blood pressure (BP) and heart rate (HR) were recorded for a further 120min. Measurements were obtained (Finometer) in both the supine (5min) and standing (5min) condition every 30min. Power spectral analysis of RR-interval and BP variability was calculated, and heart rate responses to the baroreceptor reflex were calculated to estimate spontaneous baroreflex sensitivity (sBRS). Derived stroke volume (SV) was measured to track changes to postural stress postprandially.', 'Quiet standing increased RR-interval low frequency power, ratio of RR-interval low frequency power/high frequency power (ratio of RR LF/HF), and systolic BP low frequency power (SBP LF power), and decreased RR HF power and sBRS before, and after eating. After meal ingestion, SBP LF power increased and sBRS decreased in lying and standing conditions. During quiet standing postprandially, DBP and the mean arterial pressure increased (P<0.01). The increased BP is associated with increased SV (P<0.05) early postprandially, and increased SBP LF power (P<0.01) in the later postprandial phase. SBP LF power is inversely correlated with SV postprandially (P<0.001, R(2)=0.96).']

["Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation.", 'In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1β and IL-6 genes) and NO synthesis were also examined.', "Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1β and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1α (HIF-1α) significantly increase, while the cytosol IκB-α content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IκB-α protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-κB activation and reduce the HIF-1α generation."]

Division of the PA and CC into tertiles best described the dose-response effects. After adjustment for CC, age, weight, alcohol consumption, and cigarette smoking, high PA compared with medium or low PA was associated with higher hip BMD and heel QUS (total hip BMD, 3.1%; p < 0.001; QUS stiffness, 2.7%; p = 0.002). After adjustment for PA and covariates, high or medium CC compared with low CC was associated with higher total hip BMD (1.8%; p = 0.027), with no effect at the QUS heel site. PA and CC were dichotomized at the cut-points for effects on BMD. The combination of high PA and CC, achieved by 24% of the population, was associated with a total hip BMD that was 5.1% higher (34% of SD) than those individuals in the low PA and CC group. Stiffness was 3.6% (23% of SD) higher in the high PA and CC group than in the low PA and CC group. If the whole population undertook and achieved a high PA and high CC lifestyle, the population risk of hip fractures may be expected to be reduced by about 17% in this age group as a result of beneficial effects on the musculoskeletal system.

['Downregulation of gap junctional intercellular communication (GJIC) has been implicated in carcinogenesis. This is a result of altered expression of connexins, the proteins that mediate GJIC, including connexin 43 (Cx43). Our aim was to evaluate the effect of known inducers of Cx43 on the chemosensitivity of the human neuroblastoma cell line IMR-32 to chemotherapeutic agents.', 'We examined the effect of dibutyryl-cyclic AMP (db-cAMP) and all-trans-retinoic acid (tRA) on Cx43 and GJIC, glutathione (GSH) and gamma-glutamyl-cysteine-synthetase (gamma-GCS) levels, and glutathione S-transferase (GST) activity. Finally, we performed cell survival assays to measure the response of IMR-32 cells to the chemotherapeutic drugs doxorubicin, melphalan and bis-chloronitrosourea (BCNU), after treatment with db-cAMP and/or tRA.', 'Exposure to db-cAMP led to the upregulation of GJIC and Cx43 expression and phosphorylation. On the other hand, exposure to tRA led to the upregulation of GJIC but Cx43 expression and phosphorylation were not greatly affected. The combination of both agents was more potent in inducing GJIC in comparison to treatment with db-cAMP or tRA alone. Treatment with db-cAMP, but not with tRA, was associated with a significant increase in the cytotoxic effects of the anticancer drugs doxorubicin, melphalan and BCNU as shown by a decrease in their IC50 values. Concomitant exposure to db-cAMP and tRA, however, had a more pronounced effect on cell sensitization to chemotherapy drugs (particularly doxorubicin) than exposure to db-cAMP or tRA alone. Under the db-cAMP and tRA treatment conditions (which upregulate GJIC and modulate drug response), GSH levels were significantly reduced while the levels of GST and gamma-GCS activities remained unchanged.']

['An age-period cohort model was fitted to analyse time effects on hip fracture incidence rates by sex (Portugal, 2000-2008). Rates increased exponentially with age (age effect). Incidence rates decreased after 2004 for women and were random for men (period effect). New but comprehensive fluctuations in risk were coincident with major political/economic changes (cohort effect).', 'Healthcare improvements have allowed prevention but have also increased life expectancy, resulting in more people being at risk. Our aim was to analyse the separate effects of age, period and cohort on incidence rates by sex in Portugal, 2000-2008.', 'From the National Hospital Discharge Register, we selected admissions (aged ≥ 49 years) with hip fractures (ICD9-CM, codes 820.x) caused by low/moderate trauma (falls from standing height or less), readmissions and bone cancer cases. We calculated person-years at risk using population data from Statistics Portugal. To identify period and cohort effects for all ages, we used an age-period-cohort model (1-year intervals) followed by generalised additive models with a negative binomial distribution of the observed incidence rates of hip fractures.', 'There were 77,083 hospital admissions (77.4 % women). Incidence rates increased exponentially with age for both sexes (age effect). Incidence rates fell after 2004 for women and were random for men (period effect). There was a general cohort effect similar in both sexes; risk of hip fracture altered from an increasing trend for those born before 1930 to a decreasing trend following that year. Risk alterations (not statistically significant) coincident with major political and economic change in the history of Portugal were observed around birth cohorts 1920 (stable-increasing), 1940 (decreasing-increasing) and 1950 (increasing-decreasing only among women).']

['This study sought to compare the initial success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in a native coronary artery (NCA) in patients with and without previous coronary artery bypass grafting (CABG) and to assess predictive factors.', 'Landmark novel wiring techniques for CTO-PCI have contributed to improvement in the initial success of CTO-PCI. However, challenges persist in CTO-PCI in NCA in pCABG patients.', 'Patients who underwent CTO-PCI in an NCA were selected and classified into 2 groups: pCABG (206 PCIs in 153 patients) and nCABG (1,431 PCIs in 1,139 patients).', 'CTO was located more often in the left anterior descending artery (p = 0.0003), and severe calcified lesions were observed more frequently in the pCABG group (p < 0.0001). Although the retrograde attempt was tried more frequently in the pCABG group, the CTO-PCI success rate was significantly lower in the pCABG patients than in the nCABG patients (71% vs. 83%). Longer procedural time and greater radiation exposure were needed in the pCABG patients. Logistic regression analysis among the pCABG patients revealed that intravascular ultrasound use and parallel wiring were positive factors, and lesion tortuosity was a negative factor.']

['Since intestinal epithelium expresses Toll-like receptors, it was suggested that the intestinal epithelium is actively involved in the maintenance of colonic homeostasis. Here we describe our recent findings, which support an active contribution of colonic epithelium to intestinal homeostasis via a unique activation of epithelial TLR9.', 'Recent data indicate that stimulation of Toll-like receptors by intestinal microbiota supports colonic homeostasis. Several Toll-like receptors are expressed in intestinal epithelium. TLR9, an intracellular protein in immune cells, is expressed on the cell surfaces of intestinal epithelium, both on the apical and the basolateral membrane. TLR9 signaling varies in a domain-specific manner; whereas JNK is activated by TLR9 ligand both apically or basolaterally, NF-kappaB is activated only via basolateral stimulation. In apical TLR9 stimulation, IkappaB is phosphorylated and ubiquitinated but is not degraded, and NF-kappaB-dependent inflammatory signals are not transduced. Stimulation of apical TLR9 compromises the inflammatory cascade induced basolaterally by several other Toll-like receptor ligands, suggesting that apical exposure to luminal microbial DNA restrains intestinal inflammation.']

['Recent studies have demonstrated that the induction of heat shock protein-72 (HSP72) by different stimuli preserves the heart function after cardioplegic arrest. Based on these findings, we investigated whether intermittent warm blood cardioplegia would induce changes in the myocardial expression of HSP72.', 'Forty patients scheduled for aortocoronary bypass were randomly assigned to receive either cold or warm intermittent blood cardioplegia. In all patients HSP72 and HSP72 mRNA were assayed in biopsies from the right atrium at baseline, and during the reperfusion period. Plasma CK-MB and troponin-T, and myocardial oxygen extraction and lactate release were also measured.', 'In both groups, myocardial expression of HSP72 increased throughout the reperfusion period, but the values of HSP72 band lengths were significantly higher in the warm group. Correspondingly, HSP72 mRNA levels increased progressively in both groups, with significant difference between groups observed in biopsies at the reperfusion. Warm blood cardioplegia was associated with lower levels of CK-MB and troponin-T. Myocardial oxygen extraction and lactate release were higher during intermittent warm cardioplegia, indicating a more profound ischemic anaerobic metabolism in the warm group.']

['Our purpose was to investigate whether markers for activation of the immune system are present in patients with preeclampsia by assessing maternal plasma and amniotic fluid for tumor necrosis factor-alpha and interleukin-1 beta.', 'Twenty-one patients with severe preeclampsia composed the study group (group A). An antepartum comparison group was composed of healthy nulliparous patients not in labor and matched for gestational age (group B). Another control group consisted of term nulliparous patients in labor with uneventful pregnancies (group C). Maternal plasma samples were collected from all patients at recruitment and from patients in groups A and C immediately after delivery and again 20 to 24 hours post partum. Amniotic fluid was also collected from patients in groups A and C during labor. All samples were collectively assayed for tumor necrosis factor-alpha and interleukin-1 beta by specific enzyme-linked immunoassays.', 'Before labor tumor necrosis factor-alpha was detected more frequently in the plasma of preeclamptic patients than in the plasma of patients in group B (12/16 vs 5/16, p < 0.05) and in higher concentrations (median 35 pg/ml vs median 0 pg/ml, p < 0.05). Although tumor necrosis factor-alpha was frequently detected in the plasma of patients in group C in early labor (16/20), concentrations were higher in the four preeclamptic patients first sampled in early labor (210 pg/ml vs 65 pg/ml, p < 0.05). Similarly, amniotic fluid levels of tumor necrosis factor-alpha were increased in preeclamptic patients compared with control patients. At delivery tumor necrosis factor-alpha was more likely to be identified in the plasma of preeclamptic patients and was found in higher concentrations, but by 20 to 24 hours post partum measurements in the preeclamptic and control patients were similar. There were no differences in the frequency with which interleukin-1 beta was detected or the concentration of interleukin-1 beta in any of the samples.']

['Spectrin, a heterodimer of alpha- and beta-subunits, is the major protein component of the red blood cell membrane skeleton. The mouse mutation, sph, causes an alpha-spectrin-deficient hereditary spherocytosis with the severe phenotype typical of recessive hereditary spherocytosis in humans. The sph mutation maps to the erythroid alpha-spectrin locus, Spna1, on Chromosome 1.', 'Scanning electron microscopy, osmotic gradient ektacytometry, cDNA cloning, RT-PCR, nucleic acid sequencing, and Northern blot analyses were used to characterize the wild type and sph alleles of the Spna1 locus.', 'Our results confirm the spherocytic nature of sph/sph red blood cells and document a mild spherocytic transition in the +/sph heterozygotes. Sequencing of the full length coding region of the Spna1 wild type allele from the C57BL/6J strain of mice reveals a 2414 residue deduced amino acid sequence that shows the typical 106-amino-acid repeat structure previously described for other members of the spectrin protein family. Sequence analysis of RT-PCR clones from sph/sph alpha-spectrin mRNA identified a single base deletion in repeat 5 that would cause a frame shift and premature termination of the protein. This deletion was confirmed in sph/sph genomic DNA. Northern blot analyses of the distribution of Spna1 mRNA in non-erythroid tissues detects the expression of 8, 2.5 and 2.0 kb transcripts in adult heart.']

['The purpose of this investigation was to determine whether rupture and repair of an abdominal aortic aneurysm induced activation of phagocyte oxidant burst, reflecting a systemic inflammatory state, when compared with elective abdominal aortic aneurysm (AAA) repair.', 'Blood samples were harvested from 22 patients with elective AAA and 15 patients with ruptured AAA. Phagocyte oxidant activity was measured in response to a panel of activators with luminol and lucigenin as chemiluminescent substrates. Activity of the complement pathways was measured with plasma levels of C3a des arg.', 'Elective AAA repair resulted in significant elevation in phagocyte count and oxidative activity after surgery in response to maximal dose phorbol myristate acetate (PMA) when compared with the baseline sample. In patients with ruptured AAA the oxidative activity of phagocytes was significantly increased in response to both unopsonized zymosan (899.8 +/- 192 ruptured vs 300 +/- 40 elective, p < 0.01) and maximal dose PMA (8769 +/- 2011 vs 3508 +/- 382, p < 0.01) compared with elective cases at the initial sampling. Phagocyte priming has occurred by way of two distinct pathways: receptor-mediated (unopsonized zymosan, CR3 receptor) and receptor-independent (PMA, protein kinase c).']

['The assessment of body posture control can be time consuming and cumbersome due to the complexity and the multimodal influence of a multiply influenced system. Various types of equine paces, such as stepping, trotting or galloping, result in acceleration and deceleration forces of different magnitude. These forces induce, in the horseman, reflexes that mediate motor activity to sustain posture balance and counterbalance the gravitational pull. However, there is a paucity of real life data regarding the extent of the various postural subsystems that are recruited to control postural balance in specific equine disciplines, such as classical dressage, show jumping, or vaulting. This study was conducted to bridge that gap.', 'The aim of this explorative study was to identify the types of the postural subsystems involved in balance control and assess the magnitude of their activities during classical dressage, show jumping, vaulting, and versatility riding.', '144 horseback riders (8.1 % males) aged 17.3 +/- 2.9 years and 38 age matched controls (non riders) were investigated. The riders studied were competing in dressage, show jumping, vaulting, and versatility. In each individual, postural control was investigated by means of the "interactive balance system (IBS)" that enabled us to determine the spectral power in the following four standard frequency bands: F 1 (0.03 - 0.1 Hz), F 2 - 4 (0.1 - 0.5 Hz), F 5 - 6 (0.5 - 1.0 Hz), and F 7 - 8 (1.0 - 3.0 Hz). In addition, three motorical output indices were calculated: heel-to-toe-ratio (HTR), synchronization of feet (SYNC), and the global stability index of postural balance (STAB). Furthermore, each individual was interviewed regarding riding time, frequency and discipline and also about other sports activities and disorders of health.', 'The mean training period of the horseback riders was 122 +/- 45.8 months, and mean weekly frequency of training was 5.5 +/- 1.8 days per week. Balance control was most effective in dressage and vaulting riders and least effective in show jumping competitors: HTR was 51 +/- 8 % (dressage), 48 +/- 8 % (show jumping), 47 +/- 8 % (versatility), 51 +/- 7 % (vaulting); SYNC was 523 +/- 124a. i. (dressage), 497 +/- 156a. i. (show jumping), 468 +/- 155a. i. (versatility), 589 +/- 126a. i. (vaulting). Spectral analysis revealed significantly higher power in F 1, F 2 - 4, and F 7 - 8 in dressage competition than in the other equestrian disciplines but not compared with the controls. Significantly differences between riders versus non riders were only found in HTR (p = 0.045) und SYNC (p = 0.009).']

['Roux-en-Y gastric bypass (RYGB) surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data.', 'Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7). Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172) of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05), including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9) and obese/diabetic (n = 5) groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2), nervonic (C24:1) acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI) and estimates for insulin resistance (HOMA-IR). Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55).']

['Allergic asthma is a T(H)2-promoted hyperreactivity with an immediate, IgE, and mast cell-dependent response followed by eosinophil-dominated inflammation and airway obstruction.', 'Because costimulation by CD28 is essential for T(H)2 but not T(H)1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite-induced airway inflammation.', 'To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site-specific mouse anti-mouse mAb blocking CD28 engagement.', 'We show that even after systemic sensitization to the allergen, interruption of CD28-mediated costimulation is highly effective in preventing airway inflammation during challenge. In addition to improving airway resistance and histopathologic presentation and reducing inflammatory infiltrates, antibody treatment during allergen challenge resulted in a marked relative increase in regulatory T-cell numbers among the CD4 T-cell subset of the challenged lung.']

['To examine evidence-based quality indicators (QIs) in US veterans with gout diagnosis, and to examine the effect of demographics, heath care utilization/access, comorbid conditions, or physican characteristics as predictors of quality of gout care.', 'Using the Minneapolis Veterans Affairs electronic medical record system, we identified a cohort of veterans receiving medication to treat gout between January 1, 1999 and December 31, 2003, and evaluated 3 recently published evidence-based QIs for gout management: QI 1 = allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric acid check within 6 months of starting a new allopurinol prescription, and QI 3 = complete blood count and creatine kinase check every 6 months for gout patients receiving prolonged colchicine therapy. We calculated the proportion of patients whose therapy adhered to each QI and to all applicable indicators (overall physician adherence). Logistic regression analysis examined association of overall physician adherence with sociodemographics, health care utilization, comorbidity, and provider characteristics.', 'Of 3,658 patients with a diagnosis of gout, 663 patients qualified for examination of >/=1 QI. Of these 663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%) of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52 adhered to QI 3. Overall physician adherence to QIs was significantly lower in older veterans and in those with more inpatient visits per year, but was higher in those with more primary care visits or more health care providers.']

['Melatonin, the main secretory product of the pineal gland, inhibits the growth of several types of cancer cells. Melatonin limits human prostate cancer cell growth by a mechanism which involves the regulation of androgen receptor function but it is not clear whether other mechanisms may also be involved.', 'Time-course and dose-dependent studies were performed using androgen-dependent (LNCaP) and independent (PC3) prostate cancer cells. Cell number, cell viability, and cell cycle progression were studied. Neuroendocrine differentiation of these cells was evaluated by studying morphological and biochemical markers. Finally, molecular mechanisms including the participation of melatonin membrane receptors, intracellular cAMP levels, and the PKA signal transduction pathway were also analyzed.', 'Melatonin treatment dramatically reduced the number of prostate cancer cells and stopped cell cycle progression in both LNCaP and PC3 cells. In addition, it induced cellular differentiation as indicated by obvious morphological changes and neuroendocrine biochemical parameters. The role of melatonin in cellular proliferation and differentiation of prostate cancer cells is not mediated by its membrane receptors nor related to PKA activation.']

['Hypertension links to a prothrombotic state driven by endothelial dysfunction, reduced fibrinolytic potential and platelet hyperactivity. We hypothesized that ramipril treatment would favourably modify the haemostatic response to a submaximal aerobic exercise session in hypertensives.', 'Twenty-four hypertensive patients underwent a submaximal exercise test before and after 13±2 months of treatment with ramipril ± hydrochlorothiazide. Hypercoagulability (prothrombin fragments [PF1+2], thrombin- antithrombin complex [TAT] and D-dimers [Dd]), fibrinolytic activity (plasmin-a2-antiplasmin complex [PAP]), endothelial function (von Willebrand factor [vWf] and soluble thrombomodulin [sTM]), and platelet function (soluble P-selectin [sPsel]) were measured before, at peak and one hour after exercise.', 'Antihypertensive treatment resulted in an increase of PAP, vWf and sTM. During the first exercise, PF1+2 were mildly increased at peak exercise (p<0.05), while D-dimers, PAP and vWf varied significantly throughout the exercise (p<0.001). During the second exercise session, PF1+2 were decreased post-exercise (p<0.05), PAP was increased at peak and post-exercise (p<0.001) and vWf was increased at peak (p<0.05) and post-exercise (p<0.001).']

['Ischemia-reperfusion injury (IRI) is a source of morbidity and mortality in many clinical scenarios, and has as one of its many consequences the induction of cellular apoptosis. Hydrogen sulfide (H2S) may decrease cellular metabolism in a reversible, nontoxic manner. An in vitro model of cutaneous tissue transplantation was developed to assess whether H2S could ameliorate cellular injury caused by IRI.', 'Human umbilical vein endothelial cells (HUVECs) were treated with media containing NaHS (0, 10 microM, 100 microM, or 1 mM) and exposed to normoxia (21% oxygen), hypoxia (1%), or anoxia (0%). Cells were then returned to normoxia, and apoptosis was quantified using a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Fibroblasts (3T3s) were treated with H2S and exposed to anoxia in a similar fashion.', 'Treatment with H2S resulted in a significant decrease in apoptosis in HUVECs and 3T3s subjected to IRI. Toxicity of H2S was not observed, although the protective effect was less evident at higher doses.']

['Brain metastases (BMs) are common in melanoma patients. Adjuvant whole brain radiotherapy (WBRT) following local treatment of intracranial melanoma metastases with neurosurgery and/or stereotactic radiosurgery is controversial. A randomised trial is needed. However, accrual to WBRT trials has been problematic. A pilot study by Australia and New Zealand Melanoma Trials Group (ANZMTG) was conducted to see if accrual was feasible.', 'Sites canvassed for interest included those who treat melanoma patients, had a proven accrual in previous melanoma trials and who had the relevant infrastructure support. Feasibility forecasts from interested sites were sought. These were compared to the patient numbers documented in the research contracts. A target accrual of 60 patients in 2 years was set. Funding was sought for the pilot study. Basic demographics of the pilot study cohort were collected.', 'The first centre opened December 2008; the first patient was randomised in April 2009. The pilot accruing period concluded in September, 2011. In 30 months, 54 patients from 10 of a total of 17 activated sites in Australia (39, 72%) and in Norway (15, 28%) had been accrued. Feasibility forecasts predicted 133 trial eligible patients per year (including 108 Australian + 25 International patients). Site estimates generally overestimated accrual with 4 of 17 active sites estimating within 50% of target numbers. Sites with patient estimates calculated from records were more accurate than those estimated from memory. The overall recruitment target was lower in the research contracts when compared to the feasibility evaluation. Basic demographics of the pilot study revealed 62% of patients were males; 58% had a single metastasis, 28% had two and 14% had three metastases. 12-month overall survival was 50%.']

['The induction of osteoarthritis-like changes by intra-articular injections of collagenase in the knee joint of mature rabbits was examined.', 'Collagenase (0.5, 1.0 or 2.0 mg) was intra-articularly injected twice into the right knee, and the cartilage and synovia was histologically examined at 6 weeks after the initiation of collagenase injections. In addition, 1 mg of collagenase was intra-articularly injected twice into rabbits, and histological examinations of the cartilage and synovia were performed at various time points. In other experiments, articular cartilage was digested in 5 ml of 0.4 mg/ml collagenase in vitro, and biochemical analyses of the cartilage were performed.', 'The degeneration of the cartilage and synovia were found to be dependent on the dose of collagenase. The cartilage degeneration of the femoral condyle and tibial plateau was more severe at the lateral side than at the medial side. The degeneration of the cartilage progressed, whereas the degeneration of the synovia lessened with time. In the biochemical analyses of the digested cartilage in vitro, the proportion of water increased, and the dry weight of the collected cartilage, the amounts of hydroxyproline and sulfated glycosaminoglycan decreased with the digesting time.']

['Passive transfer of antibodies through transfusion has been reported to cause adverse consequences. Approximately 1 in 700 individuals of Northern European ancestry lack IgA with up to 40 percent reported as having anti-IgA. Whether these antibodies when passively transfused were associated with reactions was examined.', 'Records were reviewed to identify IgA-deficient (<0.05 mg/dL detectable IgA) apheresis PLT donors with anti-IgA. Transfusion outcomes of products from these donors were compared to outcomes of control transfusions from donors who were not IgA-deficient.', 'Four IgA-deficient donors with anti-IgA donated a total of 25 apheresis PLT products transfused to 22 recipients. Of the transfused products, 1 (4.0%) was associated with fever that was classified as unrelated to transfusion. In the control group, 60 donors donated 78 apheresis PLT products transfused to 56 recipients. Among these, an allergic reaction was identified (1.3%). The reaction rates between both groups were not different whether the single event in the anti-IgA group was considered a reaction (chi-squared value 0.735, p = 0.3914) or considered unrelated to transfusion (chi-square value 0.324, p = 0.5694).']

['Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The levels and the prognostic relevance of serum endostatin in AML patient is not fully clear.', 'To evaluate serum levels of endostatin in acute myeloid leukemia patients before chemotherapy and after achieving complete remission and to correlate endostatin levels with patients outcome.', 'Serum samples from 30 adult patients (22 males and 8 females, median age 37, range 19-66 years) with AML had been taken before chemotherapy was administered. In addition 20 out of 30 patients were reinvestigated again at complete remission (CR). Ten samples from healthy normal persons of matched age and sex were evaluated as a reference control group. Serum endostatin levels were determined using enzyme linked immune sorbent assay (ELISA).', 'Endostatin serum levels were not significantly different in the pretreatment AML patients as compared to that in normal controls (P>0.05). In AML patients the baseline endostatin levels were significantly lower than at CR (P=0.001). No significant correlation were detected between pretreatment serum endostatin levels and age, peripheral blood white cell counts, platelet counts, bone marrow blast cell counts, blast cell distribution ratio. The prognostic value of sE was also evaluated by dividing AML patients into high and low sE groups using the 75 percentile sE levels of the patients group as cutoff. The authors found that patients group in the high sE group survived for significantly longer time than those patients in the low sE group.']

['In some institutions advanced metastatic germ-cell tumour (GCT) is treated with low-dose induction chemotherapy in specific settings. There is a lack of published data supporting its use. The data presented here specifically address this issue for the first time.', 'Twenty patients with metastatic GCT treated were with low-dose induction chemotherapy [Baby-BOP (bBOP)] between 1998 and 2009. We report the toxicity and outcome and compare it with a control group.', 'bBOP was well tolerated with no treatment-related deaths and a lack of chemotherapy-related toxicity. It was associated with a significant fall in tumour markers (median HCG fell from 35 195 to 11 028 IU/l). The first subsequent cycle of standard chemotherapy was administered a median of 9.5 days after initial treatment and was not associated with excess toxicity. The 2-year overall survival of the poor-prognosis patients treated with bBOP was 79.0% [95% confidence interval (CI) 48% to 93%], which is not significantly different from the 2-year overall survival of 80% [95% CI 55% to 92%] of the poor-prognosis patients, who did not receive bBOP.']

['Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by new bone formation. Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels. And miR-29a orchestrates osteoblast differentiation through direct targeting and negative regulation of Dkk-1.', 'We initially validated the expression levels of miR-29a in the peripheral blood mononuclear cells (PBMCs) of AS patients (n = 30), rheumatoid arthritis (RA) patients (n = 30) and healthy controls (n = 30) using real-time quantitative reverse transcription PCR (qRT-PCR). Correlation analysis was assessed between miR-29a level in PBMCs of AS patients and disease activity indexes, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis function index (BASFI) and modified Stoke ankylosing spondylitis spinal score (mSASSS).', 'Significantly higher expression of miR-29a was observed in PBMCs of AS patients (Ct 9.18 ± 1.96) compared with that in RA patients (10.97 ± 0.70, p < 0.001) and healthy controls (Ct 11.45 ± 1.23, p < 0.001). There was no significant difference between RA patients and healthy controls in miR-29a expression (p > 0.05). Elevated miR-29a expression is not correlated with disease activity index (p > 0.05). A weak correlation was found between elevated miR-29a expression and mSASSS (r = -0.393, p = 0.032).']

['Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined.', 'To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH.', 'Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH.', 'HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9).']

['Van Gogh-like (Vangl) 2 is a planar cell polarity (PCP) protein that regulates the induction of polarized cellular and tissue morphology during animal development. In the nervous system, the core PCP signaling proteins have been identified to regulate neuronal maturation. In axonal growth cones, the antagonistic interaction of PCP components makes the tips of filopodia sensitive to guidance cues. However, the molecular mechanism by which the PCP signaling regulates spine and dendritic development remains obscure.', 'Here we explored the finding that a loss of function of Vangl2 results in a significant reduction in spine density and complexity of dendritic branching. In spite of a previous report, in which the Vangl2 C-terminal TSV motif was shown to be required for the interaction with PSD-95 and the C-terminal intracellular domain was shown to associate with N-cadherin, overexpression of deletion mutants (Vangl2-∆TSV and Vangl2-∆C) had little effect on spine density. However, when an N-terminal region deletion mutant was overexpressed, spine density was slightly down-regulated. Intriguingly, the deletion mutants had a more potent effect on dendritic branching, such that the deletion of the N-terminal region reduced dendritic branching, whereas deletion of the C-terminal region increased it.']

['Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study.', 'To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma.', 'By using electronic pharmacy and health care data from Kaiser Permanente Southern California, 2392 patients, ages 18 to 64 years, were identified who met the Health Effectiveness Data and Information Set 2-year criteria for persistent asthma, did not manifest chronic obstructive pulmonary disease and other major illnesses, and had a blood eosinophil determination in 2010. Exacerbations (primary outcome) were defined as asthma outpatient visits that required systemic corticosteroid dispensing within ±7 days or asthma emergency department visits or hospitalizations. A period of ≥8 days defined a new exacerbation. Multivariate modelling used negative binomial and Poisson regression to examine the association between a blood eosinophil count determined in 2010 and risk of exacerbations, and ≥7 short-acting β2-agonist (SABA) canisters dispensed (secondary outcome) in 2011 by adjusting for demographics, comorbidities, and asthma burden.', 'The rate of asthma exacerbations in 2011 was 0.41 events per person year (95% CI, 0.37-0.45). Eosinophil count ≥400/mm(3) in 2010 was a risk factor for asthma exacerbations in 2011 (adjusted rate ratio 1.31 [95% CI, 1.07-1.60]; P = .009) and ≥7 SABA dispensed (adjusted risk ratio 1.17 [95% CI, 1.03-1.1.33]; P = .015).']

['Dietary intake of specific nutrients or food groups during pregnancy could play a role in the risk of asthma and atopy in offspring, but specific dietary patterns have not been implicated. The authors evaluated the impact of maternal (during pregnancy) and child adherence to a Mediterranean diet on asthma and atopy in childhood.', "Women presenting for antenatal care at all general practices in Menorca, a Mediterranean island in Spain, over a 12 month period starting in mid-1997 were recruited. 460 children were included in the analysis after 6.5 years of follow-up. Maternal dietary intake during pregnancy and children's dietary intake at age 6.5 years were assessed by food frequency questionnaires, and adherence to a Mediterranean diet was evaluated by a priori defined scores. During follow-up, parents completed questionnaires on the child's respiratory and allergic symptoms. Children underwent skin prick tests with six common aeroallergens.", 'The prevalence rates of persistent wheeze, atopic wheeze and atopy at age 6.5 years were 13.2%, 5.8% and 17.0%, respectively. One-third (36.1%) of mothers had a low quality Mediterranean diet during pregnancy according to the Mediterranean Diet Score, while the rest had a high score. A high Mediterranean Diet Score during pregnancy (at two levels, using "low" score as the reference) was found to be protective for persistent wheeze (OR 0.22; 95% CI 0.08 to 0.58), atopic wheeze (OR 0.30; 95% CI 0.10 to 0.90) and atopy (OR 0.55; 95% CI 0.31 to 0.97) at age 6.5 years after adjusting for potential confounders. Childhood adherence to a Mediterranean diet was negatively associated with persistent wheeze and atopy although the associations did not reach statistical significance.']

["To evaluate the frequency of neurobehavioral symptoms related to FTLD in a consecutive series of amyotrophic lateral sclerosis (ALS) patients and to assess their influence on patients' and caregivers' mood, burden, and quality of life.", "A total of 70 couples of ALS patients and their caregivers consecutively seen in our ALS clinic were separately interviewed using a battery of tests assessing frontotemporal-related neurobehavioral symptoms, emotional status, and quality of life. Patients' behavioral abnormalities were assessed with the Frontal Systems Behavior Scale (FrSBe). Caregiver burden was assessed with the Caregiver Burden Inventory (CBI).", "According to caregivers' evaluations, 34 (48.6%) patients had FrSBe pathological scores at the time of the interview. According to patients' evaluation, 9 (12.9%) patients had pathological scores at the time of the interview. In caregivers' assessment, at the time of the interview the most commonly impaired neurobehavioral domain was apathy (39 patients, 55.7%), followed by executive dysfunction (32, 45.7%) and disinhibition (18, 25.7%). Neurobehavioral symptoms were related to the presence of bulbar symptoms at the time of the interview, but not to patients' age, gender, or physical status (ALS-FRS score). Patients' neurobehavioral symptoms were significantly related to lower caregivers' quality of life, highest depression, and highest burden, both in univariate and in multivariable analyses."]

['Symptomatic Primary Humoral Immunodeficiency Diseases (PHID) constitute a highly heterogeneous group of diseases characterized by a shared hypogammaglobulinemia, resulting in increased risk of recurrent or severe infections. Associations have been described with a variety of immunological abnormalities involving B and T-cell differentiation, T-cell activation and innate immunity. However, PHID discrimination remains based on B-lymphocyte abnormalities and other components of the immune system have not been sufficiently taken into account. We carried out unsupervised and supervised methods for classification in a cohort of 81 symptomatic PHID patients to evaluate the relative importance of 23 immunological parameters and to select relevant markers that may be useful for diagnosis and prognosis.', 'We identified five groups of patients, among which the percentage of PHID complications varied substantially. Combining the set of markers involved in PHID supported the existence of two distinct mechanisms associated with complications. Switched memory B-cell attrition and CD8+ HLA-DR + activated T-cell increase were the prominent abnormalities observed in PHID complications. Furthermore, in a subgroup of 57 patients with common variable immunodeficiency, the classification that added CD8+ HLA-DR + to the consensual EUROclass classification was better than the EUROclass model in predicting complications.']

['Numerous studies have shown that aberrant microRNA (miRNA) expression is associated with the pathogenesis and progression of various human diseases. Hence, serum miRNAs are considered to be potential biomarkers for the diagnosis of human diseases. This study examined whether several miRNAs known to be commonly deregulated in liver diseases are deregulated in the serum of hosts with hepatic schistosomiasis, and thus whether they could serve as potential markers for detection of schistosome infection and evaluation of the effectiveness of chemotherapy.', 'We analyzed the serum levels of six selected candidate miRNA molecules (miR-146b, miR-122, miR-223, miR-199a-5p, miR-199a-3p, miR-34a) from mice, rabbits, buffalos and humans infected with Schistosoma japonicum using qPCR. We evaluated liver pathology by determining the hydroxyproline content in liver tissues. Primary resident liver cells were isolated to quantify the expression level of deregulated miRNAs. Bioinformatics analyses were also conducted to assess the potential function of miR-223.', 'Using a mouse model of Schistosoma japonicum infection, we found that the expression level of serum miR-223 was significantly elevated after infection, but returned to near normal levels after the treatment with praziquantel (PZQ). Importantly, the level of serum miR-223 reflected the extent of liver pathology post-infection. We validated the elevated level of the circulating miR-223 in serum samples of other host species including rabbits, buffalos and humans. In addition, our results showed that miR-223 was primarily located in the Kupffer cells, but its expression levels were significantly up-regulated in hepatocytes, hepatic stellate cells and Kupffer cells after infection. Bioinformatics analyses revealed a potential functional role of miR-223 in transcription regulator activity, transcription factor activity and DNA binding.']

['Chrysolaena obovata, an Asteraceae of the Brazilian Cerrado, presents seasonal growth, marked by senescence of aerial organs in winter and subsequent regrowth at the end of this season. The underground reserve organs, the rhizophores, accumulate inulin-type fructans, which are known to confer tolerance to drought and low temperature. Fructans and fructan-metabolizing enzymes show a characteristic spatial and temporal distribution in the rhizophores during the developmental cycle. Previous studies have shown correlations between abscisic acid (ABA) or indole acetic acid (IAA), fructans, dormancy and tolerance to drought and cold, but the signalling mechanism for the beginning of dormancy and sprouting in this species is still unknown.', 'Adult plants were sampled from the field across phenological phases including dormancy, sprouting and vegetative growth. Endogenous concentrations of ABA and IAA were determined by GC-MS-SIM (gas chromatography-mass spectrometry-selected ion monitoring), and measurements were made of fructan content and composition, and enzyme activities. The relative expression of corresponding genes during dormancy and sprouting were also determined.', 'Plants showed a high fructan 1-exohydrolase (EC 3.2.1.153) activity and expression during sprouting in proximal segments of the rhizophores, indicating mobilization of fructan reserves, when ABA concentrations were relatively low and precipitation and temperature were at their minimum values. Concomitantly, higher IAA concentrations were consistent with the role of this regulator in promoting cell elongation and plant growth. With high rates of precipitation and high temperatures in summer, the fructan-synthesizing enzyme sucrose:sucrose 1-fructosyltransferase (EC 2.4.1.99) showed higher activity and expression in distal segments of the rhizophores, which decreased over the course of the vegetative stage when ABA concentrations were higher, possibly signalling the entry into dormancy.']

['The increasing prevalence of nonalcoholic steatohepatitis (NASH) is due to the epidemic of obesity and type 2 diabetes, both of which are associated with insulin resistance.', 'To clarify the causal relationship between insulin resistance and the development of NASH, steatohepatitis was induced in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and nondiabetic control Long-Evans Tokushima Otsuka (LETO) rats by feeding them a methionine and choline-deficient (MCD) diet. Insulin sensitivity of the rats was altered by adding a high-fat (HF) diet or the peroxisomal-proliferator activated receptor-gamma agonist pioglitazone to the MCD diet.', 'The MCD diet-induced steatohepatitis was accelerated in OLETF rats after 8 weeks. Steatosis preceded inflammation, which led to fibrosis and the development of steatohepatitis. The hepatic gene expression for transforming growth factor-beta, alpha1 procollagen and plasminogen activator inhibitor-1 was up-regulated in OLETF rats compared with LETO rats. The MCD + HF diet further enhanced insulin resistance and led to rapid development of pre-cirrhosis in OLETF rats by increasing the triglyceride pool, activating stellate cells, and up-regulating gene expression for sterol regulatory element-binding protein-1c and fatty acid synthase in the liver. In contrast, pioglitazone attenuated the MCD diet-induced steatohepatitis in OLETF rats but not in LETO rats by reversing the underlying pathogenesis involved in this model through improvement of insulin resistance. These results confirm a link between insulin resistance and the development/progression of steatohepatitis, at least partly via up-regulation of genes for lipogenesis, inflammation, and fibrogenesis, in animal models.']