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['Multiple intracellular transport pathways drive the formation, maintenance, and function of cilia, a compartmentalized organelle associated with motility, chemo-/mechano-/photosensation, and developmental signaling. These pathways include cilium-based intraflagellar transport (IFT) and poorly understood membrane trafficking events. Defects in ciliary transport contribute to the etiology of human ciliary disease such as Bardet-Biedl syndrome (BBS). In this\xa0study, we employ the genetically tractable nematode Caenorhabditis elegans to investigate whether endocytosis genes function in cilium formation and/or the transport of ciliary membrane or ciliary proteins.', 'Here we show that localization of the clathrin light chain, AP-2 clathrin adaptor, dynamin, and RAB-5 endocytic proteins overlaps with a morphologically discrete periciliary membrane compartment associated with sensory cilia. In addition, ciliary transmembrane proteins such as G protein-coupled receptors concentrate at periciliary membranes. Disruption of endocytic gene function causes expansion of ciliary and/or periciliary membranes as well as defects in the ciliary targeting and/or transport dynamics of ciliary transmembrane and IFT proteins. Finally, genetic analyses reveal that the ciliary membrane expansions in dynamin and AP-2 mutants require bbs-8 and rab-8 function and that sensory signaling and endocytic genes may function in a common pathway to regulate ciliary membrane volume.']
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["When medical students move from the classroom into clinical practice environments, their roles and learning challenges shift dramatically from a formal curricular approach to a workplace learning model. Continuity among peers during clinical clerkships may play an important role in this different mode of learning. We explored students' perceptions about how they achieved workplace learning in the context of intentionally formed or ad hoc peer groups.", "We invited students in clerkship program models with continuity (CMCs) and in traditional block clerkships (BCs) to complete a survey about peer relationships with open-ended questions based on a workplace learning framework, including themes of workplace-based relationships, the nature of work practices, and selection of tasks and activities. We conducted qualitative content analysis to characterize students' experiences.", 'In both BCs and CMCs, peer groups provided rich resources, including anticipatory guidance about clinical expectations of students, best practices in interacting with patients and supervisors, helpful advice in transitioning between rotations, and information about implicit rules of clerkships. Students also used each other as benchmarks for gauging strengths and deficits in their own knowledge and skills.']
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['Few previous studies have evaluated primary adherence (whether a new prescription is filled within 30 d) to controller medications in individuals with persistent asthma.', 'To compare adherence to the major controller medication regimens for asthma.', 'This was a retrospective cohort study of enrollees from five large health plans. We used electronic medical data on patients of all ages with asthma who had experienced an asthma-related exacerbation in the prior 12 months. We studied adherence measures including proportion of days covered and primary adherence (first prescription filled within 30 d).', 'Our population included 69,652 subjects who had probable persistent asthma and were prescribed inhaled corticosteroids (ICSs), leukotriene antagonists (LTRAs), or ICS/long-acting β-agonists (ICS/LABAs). The mean age was 37 years and 58% were female. We found that 14-20% of subjects who were prescribed controller medicines for the first time did not fill their prescriptions. The mean proportion of days covered was 19% for ICS, 30% for LTRA, and 25% for ICS/LABA over 12 months. Using multivariate logistic regression, subjects prescribed LTRA were less likely to be primary adherent than subjects prescribed ICS (odds ratio, 0.82; 95% confidence interval, 0.74-0.92) or ICS/LABA (odds ratio, 0.88; 95% confidence interval, 0.80-0.97). Black and Latino patients were less likely to fill the prescription compared with white patients.']
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['The function of peroxisome proliferator-activated receptor-gamma (PPARgamma) in hepatic inflammation and injury is unclear. In this study, we sought to determine the role of PPARgamma in hepatic ischemia/reperfusion injury in mice. Male mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. PPARgamma was found to be constitutively activated in hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic PPARgamma activation rapidly decreased and remained suppressed throughout the 8-hour reperfusion period. This reduced activation was not a result of decreased protein availability as hepatic nuclear PPARgamma, retinoid X receptor-alpha (RXRalpha), and PPARgamma/RXRalpha heterodimer expression was maintained. Accompanying the decrease in PPARgamma activation was a decrease in the expression of the natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). This was associated with reduced interaction of PPARgamma and the coactivator, p300. To determine whether PPARgamma activation is hepatoprotective during hepatic ischemia/reperfusion injury, mice were treated with the PPARgamma agonists, rosiglitazone and connecting peptide. These treatments increased PPARgamma activation and reduced liver injury compared to untreated mice. Furthermore, PPARgamma-deficient mice had more liver injury after ischemia/reperfusion than their wild-type counterparts.']
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['The stromal microenvironment has a profound influence on tumour cell behaviour. In tumours, the extracellular matrix (ECM) composition differs from normal tissue and allows novel interactions to influence tumour cell function. The ECM protein tenascin-C (TNC) is frequently up-regulated in breast cancer and we have previously identified two novel isoforms - one containing exon 16 (TNC-16) and one containing exons 14 plus 16 (TNC-14/16).', 'The present study has analysed the functional significance of this altered TNC isoform profile in breast cancer. TNC-16 and TNC-14/16 splice variants were generated using PCR-ligation and over-expressed in breast cancer cells (MCF-7, T47D, MDA-MD-231, MDA-MB-468, GI101) and human fibroblasts. The effects of these variants on tumour cell invasion and proliferation were measured and compared with the effects of the large (TNC-L) and fully spliced small (TNC-S) isoforms.', 'TNC-16 and TNC-14/16 significantly enhanced tumour cell proliferation (P < 0.05) and invasion, both directly (P < 0.01) and as a response to transfected fibroblast expression (P < 0.05) with this effect being dependent on tumour cell interaction with TNC, because TNC-blocking antibodies abrogated these responses. An analysis of 19 matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases 1 to 4 (TIMP 1 to 4) revealed that TNC up-regulated expression of MMP-13 and TIMP-3 two to four fold relative to vector, and invasion was reduced in the presence of MMP inhibitor GM6001. However, this effect was not isoform-specific but was elicited equally by all TNC isoforms.']
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['Nearly one-half of Guatemalan children experience growth faltering, more so in indigenous than in nonindigenous children.', 'On the basis of ethnographic interviews in Totonicapán, Guatemala, which revealed differences in maternal perceptions about food needs in infant girls and boys, we predicted a cumulative sex difference in favor of girls that occurred at ∼6 mo of age and diminished markedly thereafter. We examined whether the predicted differences in age-sex patterns were observed in the village, replicated the examination nationally for indigenous children, and examined whether the pattern in nonindigenous children was different.', 'Ethnographic interviews (n = 24) in an indigenous village were conducted. Anthropometric measurements of the village children aged 0-35 mo (n = 119) were obtained. National-level growth patterns were analyzed for indigenous (n = 969) and nonindigenous (n = 1374) children aged 0-35 mo with the use of Demographic and Health Survey (DHS) data.', 'Mothers reported that, compared with female infants, male infants were hungrier, were not as satisfied with breastfeeding alone, and required earlier complementary feeding. An anthropometric analysis confirmed the prediction of healthier growth in indigenous girls than in indigenous boys throughout the first year of life, which resulted in a 2.98-cm height-for-age difference (HAD) between sexes in the village and a 1.61-cm HAD (P < 0.001) in the DHS data between 6 and 17 mo of age in favor of girls. In both data sets, the growth sex differences diminished in the second year of life (P < 0.05). No such pattern was seen in nonindigenous children.']
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['Dysfunction in the ventromedial prefrontal cortex (vmPFC) is believed to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading neurocircuitry models of these disorders propose that hypoactivity in the vmPFC engenders disinhibited activity of the amygdala and, consequently, pathologically elevated levels of negative affect. This model predicts that a selective loss or diminution of function of the vmPFC would result in heightened activity of the amygdala. Although this prediction has been borne out in rodent lesion and electrophysiologic studies using fear conditioning and extinction paradigms, there has not yet been a definitive test of this prediction in humans.', 'We tested this prediction through a novel use of functional magnetic resonance imaging in four neurosurgical patients with focal, bilateral vmPFC damage.', 'Relative to neurologically healthy comparison subjects, the patients with vmPFC lesions exhibited potentiated amygdala responses to aversive images and elevated resting-state amygdala functional connectivity. No comparable group differences were observed for activity in other brain regions.']
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['Endotracheal intubation (ET) in intensive care unit (ICU) patients is regarded as more challenging than elective intubations in the operating room. Despite challenging conditions in ICU, trainees are often the initial operators performing ET. Because nonanesthesiologist intensivists with limited experience in ET run most of the nonsurgical ICUs, it is of exceptional importance to identify patients with predictable difficult ET in advance to prepare for a difficult airway scenario and thus avoid severe complications.', 'In this prospective, observational, single-center study, we used a truncated MACOCHA score to evaluate intubation performance of nonanesthesiologist ICU trainees in an interdisciplinary medical ICU.', 'We show that (a) ET could be performed safely and without fatal complications in all cases; (b) the MACOCHA score is feasible on a nonanesthesiologist ICU; (c) a truncated MACOCHA score of at least 8 predicts failure of ICU trainees; and (d) availability of an ear, nose, and throat physician and an anesthesiologist is required to warrant successful management of difficult airways.']
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['Abrus agglutinin (AGG) from the seeds of Indian medicinal plant Abrus precatorius belongs to the class II ribosome inactivating protein family. In this study we investigated the anticancer effects of AGG against human hepatocellular carcinoma in vitro and in vivo.', 'Cell proliferation, DNA fragmentation, Annexin V binding, immunocytofluorescence, Western blotting, caspase activity assays and luciferase assays were performed to evaluate AGG in human liver cancer cells HepG2. Immunohistochemical staining and TUNEL expression were studied in tumor samples of HepG2-xenografted nude mice.', 'AGG induced apoptosis in HepG2 cells in a dose- and time-dependent manner. AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9 activities and a sharp decrease in the Bcl-2/Bax ratio, indicating activation of a caspase cascade. Co-treatment of HepG2 cells with AGG and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells decreased the caspase 3/7 activity in comparison to HepG2 cells exposed only to AGG. Moreover, AGG decreased the expression of Hsp90 and suppressed Akt phosphorylation and NF-κB expression in HepG2 cells. Finally, AGG treatment significantly reduced tumor growth in nude mice bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31 and Ki-67 expression compared to levels observed in the untreated control mice bearing HepG2 cells.']
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['The ubiquitin-proteasome pathway (UPP) is an important protein quality control mechanism for selective degradation of abnormal proteins. The objective of this study was to test the hypothesis that enhancement of the UPP capacity could attenuate the accumulation and aggregation of misfolded proteins using V76D-γD-crystallin as a model substrate.', 'Wild type (wt) and V76D mutant γD-crystallin were fused to red fluorescence protein (RFP) and expressed in human lens epithelial cells. The cellular distribution of the expressed proteins was compared by fluorescence microscopy. The solubility of wt- and V76D-γD-crystallin was determined by cellular fractionation and Western blotting. Wt-γD-RFP and V76D-γD-RFP were also cotransfected along with a ubiquitin ligase (CHIP) or a ubiquitin-conjugating enzyme (Ubc5) into cells. Levels of wt- and V76D-γD-crystallin, the percentage of transfected cells with aggregates, and aggregate size were quantified and compared among different groups.', 'Wt-γD-crystallin was evenly distributed in cells, whereas V76D-γD-crystallin formed intracellular aggregates. Eighty percent of wt-γD-crystallin was detected in the soluble fraction, whereas only 7% of V76D-γD-crystallin was soluble. CHIP or Ubc5 coexpression reduced the protein level of V76D-γD and concomitantly its aggregation in transfected cells; these effects could be attenuated by proteasome inhibitor. Mutant CHIP with defect TPR (tetratricopeptide repeat) or U-box domain failed to reduce levels of V76D-γD-crystallin.']
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['The aim of the present study was to examine the effect of massage on nausea, anxiety, and depression in patients with breast cancer undergoing chemotherapy.', 'This work was a single-center, prospective, randomized, controlled trial.', 'This study was conducted in an oncology clinic, in a hospital in southwestern Sweden.', 'Thirty-nine (39) women (mean age = 51.8) with breast cancer undergoing chemotherapy were enrolled.', 'The patients were randomly assigned to a massage therapy group (20 minutes of massage on five occasions) or a control group (five 20-minute visits).', 'All patients recorded nausea and anxiety on the Visual Analogue Scale before and after each intervention. They also completed the Hospital Anxiety and Depression Scale.', 'Massage treatment significantly reduced nausea compared with control treatment (p = 0.025) when improvement was measured as a percentage of the five treatment periods. Differences in anxiety and depression between the two treatment regimes could not be statistically demonstrated.']
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['Recent evidence suggests that patients with a normal cranial CT scan after head injury can be safely discharged home from the emergency department. However, supporting data from previous studies has relied on incomplete patient follow-up. We utilized a statewide comprehensive hospital abstract reporting system (CHARS) to assess whether children with normal CT scans after head injury subsequently developed intracranial sequelae in the month following their initial injury.', 'Retrospective case-series study, with comprehensive statewide follow-up for 1 month.', 'The emergency department of a Level 1 Trauma Center in Seattle, Washington.', 'All children (n = 400) with head injury, Glasgow Coma Score of 13 to 15, and initial normal CT scan seen over a 4.5-year time period. All were matched against CHARS to evaluate admissions within 30 days after emergency department disposition. For readmissions, International Classification of Diseases (9th revision) discharge and procedure information was collected. All children were also matched against the state death files.', 'Four children were readmitted for neurologic reasons within 1 month following injury. One child on coumadin for heart disease developed a symptomatic subdural hematoma 5 days after head injury, requiring neurosurgical drainage. One child developed a symptomatic hemorrhagic contusion 3 days after injury, requiring observation only. Two children were readmitted 1 day after injury for concussive symptoms; both were discharged home after observation only. There were no deaths among the study population.']
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['We studied the effect of Lactobacillus reuteri strain SD2112 Tablets Reuterina (ERINA Co., Inc.), in suppressing H. pylori urease activity and to use the urea breath test (UBT) as a marker for the burden of infection. Method 1: Assessment of UBT and H. pylori density. Subjects were 33 H. pylori-positive patients from whom were obtained gastric biopsy specimens by upper gastrointestinal endoscopy. The correlation between UBT and H. pylori density was investigated. Individual UBT was established for each patient. Patients were divided by H. pylori density was 3 groups: Group I (low-density), Group II (moderate-density), and Group III (high-density). The individual UBTs were then correlated to the established H. pylori quantity. Method 2: Assessment of suppressive effect of L. reuteri on H. pylori urease activity. Subjects were 40 asymptomatic volunteers with an UBT exceeding 15 per thousand, randomly allocated to four groups: Subjects in Group A underwent active treatment for 4 weeks (period 1) and placebo treatment for the following 4 weeks (period 2). These in Group B underwent treatment in reverse order. Those in Group C underwent placebo. Group D consisted of volunteers with negative UBT undergoing active treatment for the full 8 weeks. Result 1: UBT was 11.6+/-2.0 per thousand, 22.1+/-2.6 per thousand, and 35.4+/-7.6 per thousand in Groups I, II, and III, showing UBT that increased significantly (I vs. II: p< 0.01 and I vs. III: p<0.05) based on H. pylori density. Result 2:Significant differences were seen in the decrease in UBT before versus after medication in Groups A and B. In Group A, lower UBT was maintained until the end of the full 8-week period. The overall decrease in UBT due to medication with L. reuteri Tablets was 69.7+/-4.0% (p<0.05).']
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['Baked egg is tolerated by a majority of egg-allergic children.', 'To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg.', 'Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance.', 'Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001).']
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['To determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.', 'Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.', 'Hiroshima University Hospital a tertiary cardiology centre.', '17 patients with angiographically normal coronary arteries.', 'Magnesium sulfate (MgSO(4)) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.', 'Diameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.', 'At a dose of 0.02 mmol/min, MgSO(4) did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO(4) caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 v baseline for all). MgSO(4) increased the changes in these parameters after the infusion of L-NMMA (p < 0.001 v baseline).']
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['We enrolled 65 to 75 year-old community-dwelling women and measured muscle power, strength, physical activity using accelerometry and tibial bone strength using peripheral quantitative computed tomography (pQCT). Muscle power contributed 6.6% of the variance in the bone strength-strain index and 8.9% in the section modulus after accounting for age, height, weight, and physical activity; moderate to vigorous physical activity was related to muscle power in the lower extremity.', 'Muscle power is associated with DXA measurements of bone mass, but it is not known whether muscle power is associated with bone strength. There are no reports of investigations that have tested the effect of muscle power on bone compartments using advanced imaging.', 'We enrolled 74 community-dwelling women aged 65-75 years. We measured muscle power and strength of leg extension using Keiser air-pressure resistance equipment. All participants wore a waist-mounted Actigraph accelerometer to record physical activity. We used peripheral quantitative computed tomography (pQCT) to measure tibial mid-shaft (50% of the site) bone strength (strength-strain index, section modulus). We used Pearson correlations and multi-level linear regression to investigate the associations between muscle and bone.', 'Muscle power contributed 6.6% (p = 0.007) of the variance in the bone strength-strain index and 8.9% (p = 0.001) the variance in the section modulus in older women after accounting for age, height, weight, and physical activity. Moderate to vigorous physical activity was significantly related to muscle power in the lower extremity (r = 0.260; p = 0.041).']
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['The aim of this study was to examine the significance of EBP50 (ezrin-radixin-moesin binding phosphoprotein 50) expression in esophageal squamous cell carcinoma (ESCC).', 'Real-time PCR (qRT-PCR), western blotting, and immunohistochemical staining were performed to detect EBP50 expression in pairs of ESCCs and matched non-tumor tissues, and the relationships between EBP50 expression and other clinical factors in ESCC were analyzed. An iRNA targeting EBP50 was transfected into EC9706 cells. MTT and plate colony assays were performed to assess the effects of EBP50 down-regulation on cell growth, and flow cytometry was used to evaluate the influence of inhibiting EBP50 on cell cycle progression.', 'The real-time PCR (qRT-PCR), western blotting, and immunohistochemical staining results showed that EBP50 expression was significantly lower in ESCCs compared to matched non-tumor tissues. In addition, decreased EBP50 expression correlated with differentiation, T stage, lymph node (LN) metastasis, and poor prognosis in patients with ESCC. The down-regulation of EBP50 may significantly promote the growth and proliferation of EC9706 cells while accelerating cell cycle progression from the G1to S phase.']
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['Helicobacter pylori infection has been described as a risk factor for hepatic encephalopathy in patients with chronic liver disease although the topic remains controversial.', 'To determine whether Helicobacter pylori infection is an independent predictive factor for encephalopathy in patients with liver cirrhosis.', 'Clinical, epidemiological, analytical and nutritional parameters of 205 patients were collected. Helicobacter pylori infection was determined by serology. Encephalopathy (grade II or higher) was clinically assessed during follow-up. The relationship between each parameter and encephalopathy was analysed by Kaplan-Meier curves and the Log rank test. The most significant parameters underwent multivariate analysis by Cox regression.', 'Twenty-five variables were related to encephalopathy in the bivariate analysis. Multivariate analysis selected five independent factors: previous bouts of encephalopathy (Odds ratio 3.79; 95% confidence interval 1.94-7.38), albumin (Odds ratio 0.86; 95% confidence interval 0.80-0.92), tricipital skin fold (Odds ratio 0.79; 95% confidence interval 0.66-0.95) chronic pulmonary disease (Odds ratio 2.78, 95% confidence interval; 1.31-5.92), and on-going alcoholism (Odds ratio 2.62; 95% confidence interval 1.16-5. BB).']
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['Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells.', 'To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system.', 'Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines.']
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['The gastrointestinal tract is the most common site of primary extranodal non-Hodgkin lymphoma, and the prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) differ in various studies.', 'We retrospectively searched for PG-DLBCL in a single institution, performed immunohistochemical analysis, classified tumor phenotype (Hans and Muris algorithms), reviewed medical records, and analyzed the clinical and immunophenotypic variables using Cox proportional hazard regression model.', 'A total of 46 cases were identified including 25 males and 21 females with a median age of 63.5; 18 (39%) were at stage I and 28 (61%) at stage II. Seven (15%) patients underwent surgery as initial treatment including total (n\xa0=\xa03, 7%) and subtotal (n\xa0=\xa04, 9%) gastrectomy. Thirty-three patients (72%) received frontline chemotherapy treatment including ten with additional rituximab (MabThera) injection, and two (6%) of these patients developed perforation after chemotherapy. Four patients passed away shortly after diagnosis and the remaining three were lost to follow-up. The overall 2- and 5- year survival rates were 55% and 50%, respectively. The expression of various differentiation markers was CD10 (25%), bcl-2 (50%), bcl-6 (84%), and MUM1 (64%). Half of the cases studied (22/44) were classified as germinal center B-cell (GCB) phenotype and the remaining half as non-GCB according to Hans algorithm; 66% and 34% cases belonged to groups 1 and 2, respectively, according to Muris algorithm. Univariate analysis showed the expression of bcl-6 by the tumor cells as a favorable factor, while elevated serum lactate dehydrogenase (LDH) level, bcl-2 expression, and Muris group 2 were associated with poorer outcome. Multivariate analysis revealed that the two prognostic factors were bcl-6 expression and elevated LDH level, with hazard ratios of 0.09 (p\xa0=\xa00.002) and 3.72 (p\xa0=\xa00.024), respectively.']
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['alpha 1-Antitrypsin (AAT) and alpha 2-macroglobulin (AMG) are elastase inhibitors that bind the enzyme and reduce measured levels of free elastase. It was recently demonstrated that some patients with intracranial aneurysms have significantly elevated plasma elastase (PE) levels. Although this elevation is unrelated to plasma AAT, it is unknown whether abnormal AAT phenotypes or reduced AMG levels play a role. Moreover, the pathological significance of this elevation is not understood.', 'Plasma from 24 patients with aneurysms (ruptured, n = 15; unruptured, n = 9) and 10 age-matched patients who comprised a control group was analyzed for PE and AMG levels by enzyme-linked immunosorbent assay and for AAT phenotype by isoelectric focusing. Sections of superficial temporal temporal artery obtained from these patients at the time of surgery were examined for evidence of elastin degradation by using a van Gieson stain, with scoring on a nine-point quantitative scale.', 'Patients with aneurysms showed significantly elevated PE levels (119 +/- 28 versus 17 +/- 7 micrograms/ml, P < 0.05), but AMG levels were not decreased. AAT phenotypic abnormalities were observed in 10% (2 of 20) of the patients with aneurysms, but this was not different from the expected population incidence (7%). Elastin degradation scores were significantly higher in patients with aneurysms than in patients control group (4.26 +/- 0.54 versus 1.21 +/- 0.43, P < 0.05). In addition, patients with higher elastase levels (> 80 micrograms/ml) demonstrated 55% higher degradation scores than did those with lower elastase levels (< 80 micrograms/ml).']
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['Respiratory alterations have been associated with subsequent coronary heart diseases in numerous population-based studies. The underlying mechanisms remain largely unknown. The objective of this study was to examine the association between bronchial hyperresponsiveness (BHR) to methacholine (which reflects local inflammation in the bronchus) and common carotid intima-media thickness (CCA-IMT).', 'As part of the European Community Respiratory Health Survey follow-up, in Paris Center, we assessed BHR to methacholine (> or =20% decrease in FEV1 for a maximum methacholine dose of 4 mg) and measured CCA-IMT by ultrasonography in 255 adults free of cardiovascular diseases aged 29 to 56 years (123 men, 132 women; mean age 44.5 years, 43.5% never smokers). In men, CCA-IMT mean value was higher in subjects with BHR than in those without (0.68+/-0.11 versus 0.62+/-0.09 mm, P=0.002). No association was found in women. Multivariate analysis confirmed the independent association between BHR and CCA-IMT in men (adjusted odds ratio for a 0.10-mm increase in CCA-IMT=2.1, 95% confidence interval: 1.1 to 4.3; P=0.02). These results remained similar after exclusion of asthmatic subjects (n=11). In each strata of smoking status (nonsmoker, ex-smoker, and current smokers), CCA-IMT mean values tended to be higher in subjects with BHR than in those without, although the difference between the 2 groups was more pronounced in current smokers.']
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['To investigate aerobic capacity with and without an ankle-foot orthosis (AFO) in subacute hemiparetic stroke patients.', 'Prospective crossover intervention study.', 'Rehabilitation clinic in secondary care.', 'Patients diagnosed with first-ever cerebral stroke involving the cortical or subcortical area resulting in hemiparesis (n\xa0=\xa015, 8 men and 7 women; average age, 62.1 years).', 'All subjects participated in 2 continuous, symptom-limited, low-velocity graded treadmill exercise stress tests under 2\xa0different conditions, namely, with and without an AFO. The rest interval between tests was at least 48 hours. The order of exercise stress tests was randomized.', 'To assess cardiorespiratory responses, oxygen consumption, heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and respiratory exchange ratio were measured continuously throughout the test, and peak values were obtained. The rating of perceived exertion was recorded immediately after each test. The percentage of the age-predicted maximal heart rate and total exercise duration were also measured. Gait function was assessed by the Six-Minute Walk Test.', 'Using an AFO significantly increased peak oxygen consumption and Six-Minute Walk Test results. Peak values of each of\xa0heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and respiratory exchange ratio, rating of\xa0perceived exertion, percentage of age-predicted maximal heart rate, and total exercise duration were similar regardless of AFO use.']
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['The objective of the present study was to elucidate the separate effects of energy restriction and weight loss on blood pressure (BP) and to assess the relationship between sodium intake, weight loss, and BP.', 'Two hundred and eight overweight and obese subjects (age: 52.4 +/- 0.8 yrs; BMI 33.6 +/- 0.3 kg/m(2)) completed a weight loss diet program consisting of 8-12 weeks of moderate energy restriction (ER; approximately 30% energy deficit, unrestricted salt intake) and four weeks of energy balance (EB). Body weight and BP were measured at baseline, the midpoint, and the end of ER and after EB. 24-hr Na+ excretion was measured at baseline and at the end of EB.', 'Overall, body weight reduced progressively by 7.0 +/- 0.2 kg (7.5%; p < 0.001) with the hypocaloric diet. BP fell substantially during the first phase of ER (-5.7 +/- 0.7/-2.6 +/- 0.4 mmHg, p = 0.001), corresponding to a 4.5 +/- 0.2 kg weight reduction, with no further BP changes during the second phase of ER, despite further weight loss (2.4 +/- 0.1 kg). During EB, BP remained stable. The hypotensive effects of caloric restriction and weight loss were similar across clinical subgroups defined by age, sex, diabetes, insulin sensitivity, and hypertensive status. BP responses to weight loss were independent of 24-hr urinary Na+ excretion. 24-hr urinary Na+ excretion was similar at baseline and at the end of EB (146.5 +/- 5.3 vs. 146.9 +/- 5.3 mmol/24-hr).']
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['Hypermethylation of DNA silences gene expression and is an important event in colorectal cancer (CRC). This study aimed to identify aberrantly methylated genes that contribute to a poor prognosis for patients with CRC.', 'The study comprehensively explored DNA methylation microarray profiles from 396 CRC samples and 45 normal control samples in a database and selected aberrantly methylated transcription factors associated with prognosis and metastasis. Using quantitative reverse transcription polymerase chain reaction, the identified genes in 140 patients with CRC were validated to assess the relationship between expression of methylated genes and prognosis.', 'In the study, FOXE1 was newly identified as a gene associated with prognosis and metastasis in CRC. Expression of FOXE1 in CRC tissues was significantly lower than in normal colorectal tissues (p\xa0=\xa00.01). The survival rate for the patients with low expression of FOXE1 was significantly lower than that for patients with high expression of FOXE1 in uni- and multivariate analyses. Inhibition of DNA methylation recovered FOXE1 expression in CRC cells.']
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['X chromosome inactivation is the transcriptional silencing of one X chromosome in the somatic cells of female mammals. In eutherian mammals (e.g. humans) one of the two X chromosomes is randomly chosen for silencing, with about 15% (usually in younger evolutionary strata of the X chromosome) of genes escaping this silencing. In contrast, in the distantly related marsupial mammals the paternally derived X is silenced, although not as completely as the eutherian X. A chromosome wide examination of X inactivation, using RNA-seq, was recently undertaken in grey short-tailed opossum (Monodelphis domestica) brain and extraembryonic tissues. However, no such study has been conduced in Australian marsupials, which diverged from their American cousins ~80 million years ago, leaving a large gap in our understanding of marsupial X inactivation.', "We used RNA-seq data from blood or liver of a family (mother, father and daughter) of tammar wallabies (Macropus eugenii), which in conjunction with available genome sequence from the mother and father, permitted genotyping of 42 expressed heterozygous SNPs on the daughter's X. These 42 SNPs represented 34 X loci, of which 68% (23 of the 34) were confirmed as inactivated on the paternally derived X in the daughter's liver; the remaining 11 X loci escaped inactivation. Seven of the wallaby loci sampled were part of the old X evolutionary stratum, of which three escaped inactivation. Three loci were classified as part of the newer X stratum, of which two escaped inactivation. A meta-analysis of previously published opossum X inactivation data revealed that 5 of 52 genes in the old X stratum escaped inactivation."]
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['To explore the efficacy of inductible nitric oxide synthase (iNOS) inhibitor 1400W in vivo in blocking the death pathway of lipopolysaccharide (LPS)-induced activated-microglia to preoligodendrocytes (preOLs) in neonatal rats with infective-type periventricular leukomalacia (PVL) induced by LPS.', 'Two-day-old neonatal rats were randomly divided into: a sham-operated group, an untreated PVL group, and four 1400W-treated PVL groups that were subcutaneously administrated with 20 mg/kg of 1400W at 0 h, 8 hrs, 16 hrs, and 24 hrs after LPS induction, respectively. The brain specimens were obtained 5 days after LPS induction. The pathological assessment of cerebral white matter was performed under a light microscope. Concentrations of nitric oxide (NO) were measured by nitric acid-deoxidize colorimetry. Synthesis of iNOS was determined by Western blot analysis. Peroxynitrite (ONOO(-)) level and the amount of preOLs were determined by immunocytochemistry. RETHODS: The obvious injuries of periventricular white matter, massive loss of positive O4-labelled preOLs, and increased levels of NO, ONOO(-) and iNOS were observed in neonatal rats with PVL. Compared to the untreated PVL group, the use of 1400W at 0 h, 8 hrs and 16 hrs after LPS induction significantly improved white matter injuries, reduced the levels of NO, ONOO(-) and iNOS, and increased the amount of O4-labelled preOLs. However, the use of 1400W at 24 hrs after LPS induction did not result in the improvements.']
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['The precise pathophysiological mechanisms of radiation-induced lung injury are poorly understood, but have been shown to correlate with dysregulation of different cytokines. The purpose of this study was to evaluate the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF-)alpha, interleukin-(IL-)1alpha and IL-6 after whole-lung irradiation.', 'The thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8, 16, and 24 weeks post irradiation (p. i.). Real-time multiplex RT-PCR (reverse transcriptase polmyerase chain reaction) was established to evaluate the expression of TNF-alpha, IL-1alpha and IL-6 in the lung tissue of the mice. For histological analysis, lung tissue sections were stained by hematoxylin and eosin.', 'Multiplex RT-PCR analysis revealed a biphasic expression of these pro-inflammatory cytokines in the lung tissue after irradiation. After an initial increase at 1 h p. i. for TNF-alpha and at 6 h p. i. for IL-1alpha and IL-6, the mRNA expression of these pro-inflammatory cytokines returned to basal levels (48 h, 72 h, 1 week, 2 weeks p. i.). During the pneumonic phase, TNF-alpha, IL-1alpha and IL-6 were significantly elevated and revealed their maximum at 8 weeks p. i. Histopathologic evaluation of the lung sections obtained within 4 weeks p. i. revealed only minor lung damage in 5-30% of the lung tissue. By contrast, at 8, 16, and 24 weeks p. i., 70-90% of the lung tissue revealed histopathologically detectable organizing alveolitis.']
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['The gene for the renal phosphate wasting disorder autosomal-dominant hypophosphatemic rickets (ADHR) is FGF23, which encodes a secreted protein related to the fibroblast growth factors (FGFs). We previously detected missense mutations R176Q, R179W, and R179Q in FGF23 from ADHR kindreds. The mutations replace R residues within a subtilisin-like proprotein convertase (SPC) cleavage site 176RHTR-179 (RXXR motif). The goal of these studies was to determine if the ADHR mutations lead to protease resistance of FGF-23.', 'The ADHR mutations were introduced into human FGF-23 cDNA clones with or without an N-terminal FLAG tag by site-directed mutagenesis and were transiently transfected into HEK293 cells. Protein expression was determined by Western analyses.', 'Antibodies directed toward the C-terminal portion of FGF-23 revealed that the native FGF-23 protein resolved as 32 kD and 12 kD species in HEK293 conditioned media; however, the three mutated proteins were detected only as the 32 kD band. An N-terminal FLAG-tagged native FGF-23 resolved as two bands of 36 kD and 26 kD when detected with a FLAG antibody, whereas the R176Q mutant resolved primarily as the 36 kD protein species. Cleavage of FGF-23 was not enhanced by extracellular incubation of FGF-23 with HEK293 cells. Native and mutant FGF-23s bound heparin.']
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['To examine serum creatine kinase (CK) activity after resistance exercise bouts with different rest intervals between sets and exercises in high responding (HR) and normal responding (NR) subjects.', 'During each resistance exercise bout, three sets with 10-repetition maximum (10RM) loads were completed for the chest press, cable pulldown, biceps curl, triceps extension, leg extension, and prone leg curl. Each bout differed in the length of the rest interval between sets and exercises, specifically either 1 or 3 min. After blood analysis, subjects were separated into NR or HR on the basis of the peak serum CK activity being in the 90th percentile.', 'The volume completed (load x sets x repetitions) was significantly greater for the 3-min bout versus the 1-min bout, with no significant differences between the HR and the NR groups. For the NR group, serum CK was significantly elevated from 24 to 72 h after each bout, with no significant differences between bouts. Conversely, for the HR group, the 1-min bout resulted in serum CK activity levels that were approximately 70% greater than the 3-min bout at the 48- and 72-h time points.']
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['Prevalence data of herpes simplex virus (HSV) in oral mucositis in children on treatment for cancer is limited. Quantitative polymerase chain reaction (PCR) has been seldom utilized for detection of HSV-1/2 in oral mucosa.', 'Children on treatment for cancer with oral mucositis were enrolled as cases and healthy children as controls. An oral swab from the lesion in cases and mucosal scraping in controls were obtained. Both qualitative and real-time quantitative PCR for HSV-1/2 were performed. Serum ELISA-IgG/IgM for HSV-1/2 antibodies (NovaLisa™-Dietzenbach-Germany) were measured.', 'Thirty-two cases (Age, 6.3±3.4 years) and 30 controls were enrolled. Majority (69%) of cases had ALL. All patients had febrile neutropenia, except two. ELISA-IgM-HSV-1/2 was not positive in any case or control. ELISA-IgG-HSV-1/2 was positive in 11 (34%) cases and nine (30%) controls (p=1.0). Qualitative PCR for HSV-1 detected the virus in eight (25%) cases and nil controls (p=0.009). HSV-2 was not detected in any case/control by qualitative PCR. Quantitative PCR detected HSV-1 in 21 (66%) and HSV-2 in 22 (69%) cases. In controls, quantitative PCR detected HSV-1 in three (10%) and HSV-2 in none. In patients, the mean viral load of HSV-1 (5,500±15,987×10(4) copies/nanogram DNA) was more than HSV-2 (4.03±8.5×10(4)) (p=0.11). There was no correlation of HSV-1/2 with grading of mucositis.']
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['Long intervening non-coding RNAs (lincRNAs) are a recently discovered subclass of non-coding RNAs. LincRNAs are expressed across the mammalian genome and contribute to the pervasive transcription phenomenon. They display a tissue-specific and species-specific mode of expression and are present abundantly in the brain.', 'Here, we report the expression patterns of oligodendrocyte maturation-associated long intervening non-coding RNA (OLMALINC), which is highly expressed in the white matter (WM) of the human frontal cortex compared to the grey matter (GM) and peripheral tissues. Moreover, we identified a novel isoform of OLMALINC that was also up-regulated in the WM. RNA-interference (RNAi) knockdown of OLMALINC in oligodendrocytes, which are the major cell type in the WM, caused significant changes in the expression of genes regulating cytostructure, cell activation and membrane signaling. Gene ontology enrichment analysis revealed that over 10% of the top 25 up- and down-regulated genes were involved in oligodendrocyte maturation. RNAi experiments in neuronal cells resulted in the perturbation of genes controlling cell proliferation. Furthermore, we identified a novel cis-natural antisense non-coding RNA, which we named OLMALINC-AS, which maps to the first exon of the dominant isoform of OLMALINC.']
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['To investigate the role of T cell induction of matrix metalloproteinase 13 (MMP-13) production by human osteoblasts in order to better understand the process of bone loss in rheumatoid arthritis (RA).', 'Activated T cell-conditioned medium (ACTTCM) was used to mimic the physiologic conditions of inflammation. MMP-13 production by human osteoblasts was assessed using a specific enzyme-linked immunosorbent assay. Specific inhibitors of the p38 mitogen-activated protein (MAP) kinase and the extracellular signal-regulated kinase 1/2 (ERK-1/2) MAP kinase signaling pathways were used to assess their roles in T cell-mediated MMP-13 production. Finally, recombinant cytokines representative of the major components in ACTTCM were assessed for their ability to induce MMP-13.', 'ACTTCM powerfully induced MMP-13 in human osteoblasts. Inhibition of p38 activity abolished, while inhibition of ERK-1/2 activity enhanced, MMP-13 production. We next investigated physiologic levels of the T cell cytokines tumor necrosis factor alpha (TNFalpha), transforming growth factor beta (TGFbeta), interferon-gamma (IFNgamma), and interleukin-17 (IL-17) for their roles in MMP-13 induction. Although individual cytokines had no significant effect, the combination of TNFalpha, TGFbeta, IFNgamma, and IL-17 resulted in a dramatic p38-dependent induction of MMP-13 identical to that produced by ACTTCM.']
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['The balance between apoptosis susceptibility and efferocytosis of macrophages is central to plaque remodeling and inflammation. LRP-1 and its ligand, apolipoprotein E, have been implicated in efferocytosis and apoptosis in some cell types. We investigated the involvement of the macrophage LRP-1/apolipoprotein E axis in controlling plaque apoptosis and efferocytosis. Method and Results- LRP-1(-/-) macrophages displayed nearly 2-fold more TUNEL positivity compared to wild-type cells in the presence of DMEM alone or with either lipopolysaccharide or oxidized low-density lipoprotein. The survival kinase, phosphorylated Akt, was barely detectable in LRP-1(-/-) cells, causing decreased phosphorylated Bad and increased cleaved caspase-3. Regardless of the apoptotic stimulation and degree of cell death, LRP-1(-/-) macrophages displayed enhanced inflammation with increased IL-1 beta, IL-6, and tumor necrosis factor-alpha expression. Efferocytosis of apoptotic macrophages was reduced by 60% in LRP-1(-/-) vs wild-type macrophages despite increased apolipoprotein E expression by both LRP-1(-/-) phagocytes and wild-type apoptotic cells. Compared to wild-type macrophage lesions, LRP-1(-/-) lesions had 5.7-fold more necrotic core with more dead cells not associated with macrophages.']
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['Epileptogenesis is a hallmark of severe cortical trauma, with up to approximately 80% of patients experiencing seizures in the first 24 hours after penetrating head injury. An in vitro model of traumatic brain injury was developed to investigate hyperexcitability and epileptogenesis and their prevention. We determined whether sodium valproate would prevent epileptiform activity in this experimental model.', 'Rat cortical slices were prepared and maintained in vitro using standard methods. Trauma was effected by removing the superficial 450-500 microm of slices. Traumatized slices were exposed to valproate at various time points. Intracellular and extracellular recordings were used to assess evoked activities.', 'In untreated traumatized deep segments, hyperexcitability was manifested by depressed inhibition and often (54%) by epileptiform activity. Preparations exposed to valproate at 30 minutes or later after trauma showed abnormal activity similar to control traumatized slices. Epileptogenicity in deep segments was significantly reduced when slices were exposed to valproate (a) continuously immediately after trauma, (b) after a 20-minute delay, or (c) immediately after trauma for 1 hour and then returned to physiological solution. Finally, slices that were exposed to valproate or pentobarbital beginning 20 minutes after trauma for only 1 hour and then returned to physiological medium showed a significant reduction in abnormal activity. Valproate was found to enhance fast gamma-aminobutyric acid(A)-ergic inhibitory strength.']
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['The current study was performed to evaluate whether baseline acute and chronic prostate inflammation among men with an initial negative biopsy for prostate cancer (PCa) increased the risk of subsequent PCa detection in a clinical trial with systematic biopsies.', 'A retrospective analysis was performed of 6238 men aged 50 years to 75 years with prostate-specific antigen levels between 2.5 ng/mL and 10 ng/mL and a prior negative biopsy in the REduction by DUtasteride of PCa Events study who completed a 2-year biopsy. PCa, acute prostate inflammation, and chronic prostate inflammation were assessed by central review. The association between inflammation in baseline prostate biopsies and positive 2-year and 4-year repeat biopsies was evaluated with the chi-square test and logistic regression analysis adjusting for baseline covariates.', 'Acute and chronic inflammation and both were detected in 46 baseline biopsies (1%), 3931 baseline biopsies (63%), and 892 baseline biopsies (14%), respectively. Acute and chronic inflammation were found to be significantly associated with each other (P<.001). Acute inflammation at baseline biopsy was associated with younger age, lower prostate-specific antigen levels, and a smaller prostate (all P<.01), whereas chronic inflammation was associated with older age and larger prostate glands (all P<0.01). At the 2-year biopsy, the prevalence of PCa was 14% (N=900 patients). On univariable and multivariable analysis, both acute and chronic inflammation were found to be significantly associated with a lower PCa risk (acute univariable: odds ratio [OR], 0.65 [P<.001] and multivariable: OR, 0.75 [P=.012] and chronic univariable: OR, 0.61 [P<.001] and multivariable: OR, 0.65 [P<.001]). At the time of 4-year biopsy, only acute inflammation was found to be associated with a lower PCa risk.']
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['A recent prospective, multicenter, randomized controlled trial found that 4 days of antibiotics after source control of complicated intra-abdominal infections resulted in similar outcomes when compared with longer duration. We hypothesized that the subset of patients presenting with sepsis have similar outcomes when treated with the shorter course of antibiotics.', 'Patients from the STOP-IT (Study to Optimize Peritoneal Infection Therapy) trial database meeting criteria for sepsis (ie, temperature <36°C or >38°C and a WBC count <4000 cells/mm(3) or >12,000 cells/mm(3)) were analyzed. Patients had been randomized to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 calendar days of therapy (n\xa0= 45), or to receive a fixed short-course of antibiotics for 4 ± 1 calendar days (n\xa0= 67). Outcomes included incidence of and time to surgical site infection, recurrent intra-abdominal infection, Clostridium difficile infection, and extra-abdominal infections, as well as hospital days and mortality.', 'One hundred and twelve of the 588 patients in the STOP-IT database met criteria for sepsis and were adherent to the protocol. With regard to short- vs long-course therapy, surgical site infection (11.9% vs 8.9%; p\xa0= 0.759), recurrent intra-abdominal infection (11.9% vs 13.3%; p\xa0= 1.00), extra-abdominal infection (11.9% vs 8.9%; p\xa0= 0.759), hospital days (7.4\xa0± 5.5 days vs 9.0 ± 7.5 days; p\xa0= 0.188), days to recurrent intra-abdominal infection (12.5 ± 6.6 days vs 18.0 ± 8.1 days; p\xa0= 0.185), days to extra-abdominal infection (12.6 ± 5.8 days vs 17.3 ± 3.9 days; p\xa0= 0.194), and mortality (1.5% vs 0%; p\xa0= 1.00) were similar. There were no cases of C difficile infection. Days to surgical site infection (6.9 ± 3.5 days vs 21.3 ± 6.1 days; p < 0.001) were fewer in the 4-day therapy group.']
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['Although serum ferritin measurement is the investigation of choice in iron deficiency, many laboratories continue to offer iron and TIBC/transferrin measurements. With increasing use of direct transferrin measurement, the possibility of reporting transferrin concentration alone without iron or transferrin saturation arises. This study compared the diagnostic utility of iron, transferrin and transferrin saturation measurements in the diagnosis of iron deficiency', 'Details of all laboratory requests for simultaneous serum iron, transferrin/TIBC and ferritin measurement were analysed to assess the diagnostic performance of iron, transferrin or TIBC, and transferrin saturation or TIBC saturation in identifying unequivocal iron deficiency (using 2 different serum ferritin cutoffs: <12 and <15 microg/l). The dataset was divided into 3 groups based on various reagent combinations.', 'Across inpatient and outpatient populations and all 3 reagent combinations, transferrin or TIBC measurement outperformed iron measurement and saturation index. Mean areas under ROC curves across the study were: transferrin or TIBC: 0.94; Fe 0.77; saturation 0.87. There was no difference in diagnostic performance between transferrin and the 2 TIBC formulations.']
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['Niacin reduces vascular oxidative stress and down regulates inducible nitric oxide synthase, an enzyme mediating proatherosclerotic effects in part by increasing oxidative stress. Here, we evaluate whether Niacin reverses the redox sensitive migratory arrest of macrophages in response to oxidised(ox) LDL uptake.', 'Migration of RAW264.7 cells, a murine macrophage cell line and bone marrow derived macrophages from wildtype and iNOS knockout mice was quantified using a modified Boyden chamber. Unstimulated cells or cells preincubated with oxLDL or non-oxidised (n)LDL were treated with Nicotinic acid or Nicotinamide. Nitric oxide, peroxynitrite and ROS production were assessed using electron paramagnetic resonance (ESR). Additionally, flow cytometry analysis of apoptosis, fokal adhesion kinase (FAK), phalloidin, CD36, F4/80 macrophage marker and iNOS gene expression (PCR) were assessed.', 'Migration of Nicotinic acid, Nicotinamide treated cells or unstimulated cells did not differ (P>0.05). oxLDL treatment significantly reduced migration vs. unstimulated cells (p<0.05). In contrast, migratory arrest in response to oxLDL treatment was reversed by co-incubation with Nicotinic acid and Nicotinamide. The oxLDL-induced peroxynitrite formation in RAW264.7 cells was abolished by Niacin and glutathion (GSH) oxidation was significantly reduced. However, nitric oxide (NO)- and reactive oxygen species (ROS) production induced by oxLDL were not affected by Niacin treatment of RAW264.7 cells. In addition, Nicotinic acid and Nicotinamide reduced actin polymerization, a marker for migratory arrest.']
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['Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7(KO)) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.', 'We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.']
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['Laparoscopic hernia repair with percutaneous ligation of the patent processes vaginalis is a minimally invasive alternative to open inguinal herniorrhaphy in children. With the camera port concealed at the umbilicus, this technique offers an excellent cosmetic result. It is also faster than the traditional laparoscopic repair with no differences in complication rates or hospital stay. The goal of this study was to describe a series of consecutive patients, emphasizing the impact of suture materials (absorbable vs. non-absorbable) on hernia recurrences.', 'A retrospective review was performed of consecutive transperitoneal laparoscopic subcutaneous ligations of a symptomatic hernia and/or communicating hydrocele by 4 surgeons. Patients > Tanner 2 or with prior hernia repair were excluded. The success of the procedure and number of sutures used was compared between cases performed with absorbable vs. non-absorbable suture. Risk factors for surgical failure (age, weight, number of sutures used, suture type) were assessed with logistic regression.', '94 patients underwent laparoscopic percutaneous hernia ligation at a mean age of 4.9 years. Outcomes in 85 (90%) patients with 97 hernia repairs at a mean of 8 months after surgery revealed 26% polyglactin vs 4% polyester recurrences (p = 0.004) which occurred at mean of 3.6 months after surgery, Table 1. Repairs performed with non-absorbable suture required only 1 suture more often than those performed with absorbable suture (76% vs 60%, p = 0.163). Logistic regression revealed suture type was an independent predictor for failure (p = 0.017). Weight (p = 0.249), age (p = 0.055), and number of sutures (p = 0.469) were not significantly associated with recurrent hernia.']
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['The purpose of this study was to examine the associations of sleep disturbances during pregnancy with cesarean delivery and preterm birth.', "In this prospective study, 688 healthy women with singleton pregnancy were selected from three hospitals in Chengdu, China 2013-2014. Self-report questionnaires, including the sleep quantity and quality as well as exercise habits in a recent month were administered at 12-16, 24-28, and 32-36 weeks' gestation. Data on type of delivery, gestational age, and the neonates' weight were recorded after delivery. After controlling the potential confounders, a serial of multi-factor logistic regression models were performed to evaluate whether sleep quality and quantity were associated with cesarean delivery and preterm birth.", 'There were 382 (55.5%) women who had cesarean deliveries and 32 (4.7%) who delivered preterm. Women with poor sleep quality during the first (OR: 1.87, 95% CI [1.02-3.43]), second (5.19 [2.25-11.97]), and third trimester (1.82 [1.18-2.80]) were at high risk of cesarean delivery. Women with poor sleep quality during the second (5.35 [2.10-13.63]) and third trimester (3.01 [1.26-7.19]) as well as short sleep time (<7\u2009h) during the third trimester (4.67 [1.24-17.50]) were at high risk of preterm birth.']
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[": Cellular proliferation is a key factor in the enlargement of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). We determined the extent to which adenosine 3':5'-cyclic monophosphate (cAMP) may regulate the in vitro proliferation of cyst epithelial cells derived from human ADPKD cysts.", ': Epithelial cells from cysts of individuals with ADPKD and from normal human kidney cortex (HKC) of individuals without ADPKD were cultured. The effects of agonists and inhibitors on the rate of cellular proliferation and the activation of extracellular signal-regulated kinase (ERK1/2) were determined.', ': 8-Br-cAMP (100 micromol/L) stimulated the proliferation of cells from eight different ADPKD subjects to 99.0% above baseline; proliferation was inhibited by protein kinase A (PKA) antagonists H-89 (97%) and Rp-cAMP (90%). Forskolin (10 micromol/L), which activates adenylyl cyclase, increased proliferation 124%, and receptor-mediated agonists arginine vasopressin, desmopressin, secretin, vasoactive intestinal polypeptide, and prostaglandin E2 stimulated proliferation 54.2, 56.3, 46.7, 37.1, and 48.3%, respectively. The mitogen extracellular kinase (MEK) inhibitor PD98059 completely inhibited ADPKD cell proliferation in response to cAMP agonists, but genistein, a receptor tyrosine kinase inhibitor, did not block cAMP-dependent proliferation. cAMP agonists increased the activity of ERK above control levels within five minutes. In contrast to ADPKD, proliferation and ERK activity of cells derived from normal HKC were not stimulated by cAMP agonists, although electrogenic Cl- secretion was increased by these agonists in both ADPKD and HKC cell monolayers.']
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['The haematopoietic activity of erythropoietin (EPO) is mediated by the classic EPO receptor (EpoR) homodimer, whereas tissue-protective effects are mediated by a heterocomplex between EpoR and the β-common receptor (βcR). Here, we investigated the effects of a novel, selective ligand of this heterocomplex - pyroglutamate helix B surface peptide (pHBSP) - in mice fed a diet enriched in sugars and saturated fats.', 'Male C57BL/6J mice were fed a high-fat high-sucrose diet (HFHS) for 22 weeks. pHBSP (30\u2009μg·kg(-1) s.c.) was administered for the last 11 weeks. Biochemical assays, histopathological and immunohistochemical examinations and Western blotting were performed on serum and target organs (liver, kidney and skeletal muscle).', 'Mice fed with HFHS diet exhibited insulin resistance, hyperlipidaemia, hepatic lipid accumulation and kidney dysfunction. In gastrocnemius muscle, HFHS impaired the insulin signalling pathway and reduced membrane translocation of glucose transporter type 4 and glycogen content. Treatment with pHBSP ameliorated renal function, reduced hepatic lipid deposition, and normalized serum glucose and lipid profiles. These effects were associated with an improvement in insulin sensitivity and glucose uptake in skeletal muscle. Diet-induced overproduction of the myokines IL-6 and fibroblast growth factor-21 were attenuated by pHBSP and, most importantly, pHBSP markedly enhanced mitochondrial biogenesis in skeletal muscle.']
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['To measure the change in plasma vascular endothelial growth factor (VEGF) levels after radical prostatectomy (RP) and to examine the association of pre-RP VEGF levels with known prognostic factors.', 'Plasma was collected from patients in two separate cohorts. The first cohort included 86 patients who consented to give blood before and after RP. The second cohort consisted of 280 plasma samples, obtained from untreated patients with clinically localized prostate cancer. Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. The change in plasma VEGF before and 6 to 8 weeks after RP was analyzed using a Wilcoxon signed rank test. The associations between the pre-RP VEGF levels and prognostic factors were assessed with the Spearman correlation coefficient and the Kruskal-Wallis test.', 'In a cohort of 86 patients with clinically localized prostate cancer, the median preoperative VEGF level was 49.8 pg/mL. The median level 1 month after surgery was significantly lower at 39.1 pg/mL (P = 0.006, 20% decrease). A repeat analysis 6 months or more after surgery demonstrated that the percentage of decrease in the plasma VEGF levels persisted. Plasma VEGF levels were also measured in a separate cohort of 280 patients with localized prostate cancer and demonstrated no statistically significant association with risk groups or known tumor-associated prognostic factors.']
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['The objective of our study was to determine the degree to which Framingham risk estimates and the National Cholesterol Education Program (NCEP) Adult Treatment Panel III core risk categories correlate with total coronary atherosclerotic plaque burden (calcified and noncalcified) as estimated on coronary CT angiograms.', 'Coronary CT angiography was performed in 1,653 patients (1,089 men, 564 women) without a history of coronary heart disease (mean age+/-SD: men, 51.6+/-9.7 years; women, 56.9+/-10.5 years). The most common reasons for the examination were hypercholesterolemia, family history, hypertension, smoking, and atypical chest pain. The coronary tree was divided into 16 segments; four different methods were used to quantify the amount of atherosclerotic plaque or the degree of stenosis in each segment, and segment scores were combined to give total scores. Framingham risk estimates and NCEP risk categories were calculated for each patient.', "Correlation of plaque scores with the Framingham 10-year risk estimates were modest: Spearman's rho was 0.49-0.55. For all comparisons of NCEP risk categories to plaque score categories, the proportion of raw agreement, p(0), was less than 0.50. Cohen's kappa ranged from 0.18 to 0.20. Overall, 21% of the patients would have their perceived need for statins changed by using the coronary CTA plaque estimates in place of the NCEP core risk categories; 26% of the patients on statins had no detectable plaque."]
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['Although many studies have compared in vitro TB diagnostic tests with the venerable tuberculin skin test (TST), there is little understanding of the quantitative relationship between critical measures of antimycobacterial immunity used to detect TB infection. We, therefore, decided to determine the degree of redundancy between quantitative read-outs of in vivo and in vitro assays of antimycobacterial immunity.', 'We enrolled 475 healthy HIV-negative children and young adults living in a hyperendemic area of TB. We measured in vivo TST responses, and a 1:10 diluted 3- or 7-day whole-blood assay was used to determine the in vitro antigen-specific interferon (IFN)-gamma cytokine release. The frequency of antigen-specific IFN-gamma(+)CD4(+) and IFN-gamma(+)CD8(+) cells was tested using intracellular cytokine staining after 1 day incubation.', 'In vivo TST responses segregated into two well-separated groups with either no measurable response (TST induration < 5 mm; n = 164) or a normally distributed group with TST indurations > or = 5 mm with peak at 15 mm (n = 260). In vitro assays provided a less pronounced separation of responders and nonresponders. Correlation analysis of responses among persons with TST > or = 5 mm demonstrated that extent of TST response was poorly correlated with IFN-gamma release (coefficients of correlation rho = 0.17-0.22) and frequency of IFN-gamma(+)CD4(+)/CD8(+) cells (rho = 0.05-0.17) across three stimulating antigens (Mycobacterium bovis bacillus Calmette-Guérin, purified protein derivative, early-secreted antigenic target-6).']
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['Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a marker of bone resorption).', 'Male endurance athletes (n = 20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2) placebo before and 250 mg of calcium every 15 min during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000-mg·L(-1) solution. Supplementation was double-blinded, and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise.', 'CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared with placebo, calcium supplementation before exercise attenuated the increase in PTH (mean ± SE: 55.8 ± 15.0 vs 74.0 ± 14.2 pg·mL(-1), P = 0.04); there was a similar trend (58.0 ± 17.4, P = 0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa.']
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['Biliary fistulae may occur following surgical injury, abdominal trauma, or inadequate closure of a cystic duct stump. These leaks are most often managed by drainage of the associate biloma and either endoscopic sphincterotomy or placement of a biliary endoprosthesis to decrease the pressure gradient between the bile duct and the duodenum created by the muscular contraction of the ampullary sphincter. In a previous study, we demonstrated a statistically significant reduction in ductal pressures following stent placement as compared to sphincterotomy. The goal of this present study was to determine if reduction in ductal pressures correlates clinically with the resolution of biliary leaks in an animal model.', "Fourteen mongrel dogs underwent laparotomy, cholecystectomy without closure of the cystic stump, and a lateral duodenotomy to identify the major papilla. The dogs were then randomized into three groups. Group I (n = 5) was a control group undergoing closure of the duodenotomy only. Group II (n = 4) underwent sphincterotomy. Group III (n = 5) underwent placement of a 7 Fr x 5 cm biliary endoprosthesis prior to duodenotomy closure. A drain was placed adjacent to the cystic duct stump in all groups. Drain output was recorded daily. The biliary leak was considered resolved when the output was < 10 cc/day. Regardless of suspected fistula closure, the drains were not removed until 2 weeks postprocedure. Necropsy was performed to identify undrained intraperitoneal bile. Statistical analysis was performed using Student's paired t test.", 'All dogs had bile leaks identified on postoperative day 1. The number of days required for resolution of bile leak in group I (mean +/- SEM) was 7.60 +/- 0.87 days, as compared to 6.75 +/- 0.80 days for group II and 2.60 +/- 0.24 days for group III. There was no significant difference in the duration of bile leak between groups I and II (p = 0.445). Group III, however, had a significant reduction in the duration of biliary fistulae as compared to both groups I and II (p < 0.005). At autopsy, persistent bilomas were identified in 80% of group I, 25% of group II, and 0% of group III. None of the dogs showed evidence of dehisence of the duodenotomy closure site as a source of bile leak.']
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['To investigate the role of phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) inducing epithelial mesenchymal transition in human peritoneal mesothelial cells (HPMC).', 'Primary HPMC was harvested from human omental tissue and maintained under defined in vitro conditions. The expression of p-GSK-3beta and total GSK-3beta in HMPC was detected by Western blot after incubation with different concentrations (0, 5, 10, 20, and 40 mmol/L)of LiCl at different time points (0, 1, 3, 6, and 12 h). The protein expression of E-cadherin and alpha-SMA was also examined after treatment with 20 mmol/L LiCl according to different time courses. The intracellular distribution and expression of alpha-SMA were determined by indirect immunofluorescence.', 'LiCl stimulated phosphorylation of GSK-3beta and the effect was time-dependent and concentration-dependent to limited extent (P<0.05). The expression of alpha-SMA increased (P<0.05) and the expression of E-cadherin decreased significantly (P<0.05) after 24 h stimulation by 20 mmol/L LiCl. The indirect immunoflurescence showed that the expression of alpha-SMA in HPMC increased significantly after 24 h incubation with 20 mmol/L LiCl.']
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['Peripheral vasodilation response plays an important role in the pathophysiology of obesity and heart disease.', 'To evaluate the chronic effect of vitamin C (VitC) supplementation on blood pressure and on vasodilation response to mental stress.', 'In a double-blind, randomized and prospective study we evaluated obese children with 8 to 12 years in 2 similar groups: 1) supplemented with 500 mg VitC (n = 11) and 2) placebo (n = 10) for 45 days. Eight age-matched lean control children were also studied. We evaluated: mean blood pressure (MBP), heart rate (HR) and forearm blood flow by venous occlusion plethismography. Forearm vascular conductance (FVC) was calculated by: (forearm blood flow/PAM) X100.', 'On pre-intervention evaluations obese children showed higher MBP and lower FVC compared to lean control children. After intervention VitC diminished MBP at rest (81 ± 2 vs 75 ± 1 mmHg, p = 0.01), whereas placebo did not promote changes in MBP (p = 0.58). In addition, VitC promoted FVC increase at rest (3.40 ± 0.5 vs 5.09 ± 0.6 un, p = 0.04) and during the mental stress (3.92 ± 0.5 vs 6.68 ± 0.9 un, p = 0.03). Moreover, after VitC supplementation FVC levels were similar to the lean control children at rest (5.09 ± 0.6 vs 5.82 ± 0.4 un, p > 0.05) and during mental stress (6.68 ± 0.9 vs 7.35 ± 0.5 un, p > 0.05).']
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['The volume of the mucous paratubal glands and the number of the mucus-producing goblet cells in the middle ear and Eustachian tube (ET) are increased after experimental acute otitis media (AOM). The present investigation examines a potential effect of penicillin on the changes in goblet cell density and gland structures of the ET during and after AOM.', 'Middle ear inoculation of Streptococcus pneumoniae in 50 rats. Two days later, 25 rats were given penicillin V as one daily dose for 5 days. Twenty-five rats received no treatment. Five animals from each group were sacrificed on days 4, 8, 16, 90, and 180. The ET was dissected and decalcified, followed by paraffin embedding, serial transverse sectioning, and PAS/alcian blue staining. The goblet cell density and the paratubal gland composition and volume were determined in every 20th section, using a light microscope.', 'Penicillin reduced the increase of goblet cell density from day 8 and through 6 months, whereas the increase of the paratubal mucous gland volume was unaffected by treatment.']
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["Prenatal alcohol exposure can alter physical and behavioral development, leading to a range of fetal alcohol spectrum disorders. Despite warning labels, pregnant women continue to drink alcohol, creating a need to identify effective interventions to reduce the severity of alcohol's teratogenic effects. Choline is an essential nutrient that influences brain and behavioral development. Recent studies indicate that choline supplementation can reduce the teratogenic effects of developmental alcohol exposure. The present study examined whether choline supplementation during prenatal ethanol treatment could mitigate the adverse effects of ethanol on behavioral development.", 'Pregnant Sprague-Dawley rats were intubated with 6 g/kg/day ethanol in a binge-like manner from gestational days 5-20; pair-fed and ad libitum chow controls were included. During treatment, subjects from each group were intubated with either 250 mg/kg/day choline chloride or vehicle. Spontaneous alternation, parallel bar motor coordination, Morris water maze, and spatial working memory were assessed in male and female offspring.', 'Subjects prenatally exposed to alcohol exhibited delayed development of spontaneous alternation behavior and deficits on the working memory version of the Morris water maze during adulthood, effects that were mitigated with prenatal choline supplementation. Neither alcohol nor choline influenced performance on the motor coordination task.']
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['Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by high incidence of ventricular arrhythmias. Overt ARVD/C is preceded by a subclinical stage with lack of detectable ECG and structural abnormalities. Activation delay is present before structural abnormalities and is a hallmark of arrhythmogenesis. Deformation imaging may unmask activation delay in the subclinical stage.', 'Three groups were compared: (1) mutation-positive definite ARVD/C-patients fulfilling 2010 Task Force criteria (TFC) (n = 44); (2) asymptomatic mutation carriers not fulfilling TFC and without history of ventricular arrhythmias (n = 31); and (3) controls (n = 30). All underwent ECG and echocardiographic deformation imaging. As a surrogate for local activation delay the electromechanical interval (EMI) was measured, defined as time between onset-QRS and onset of shortening. Arrhythmic outcome (PVC-count, VT) of asymptomatic mutation carriers was correlated with EMI and ECG TFC.', 'In definite ARVD/C-patients, EMI was prolonged in all lateral RV segments. In asymptomatic mutation carriers, prolonged EMI was detected in the subtricuspid area in 14/31. Terminal activation duration ≥55 milliseconds (definition: supporting information) was the only ECG abnormality in this group (8/31). After a mean follow-up of 4.2 ± 3.1 years 10/31 asymptomatic mutation carriers experienced arrhythmic outcome. Prolonged subtricuspid EMI was the only parameter significantly associated with arrhythmogenesis during follow-up.']
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['Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG orientation, the repeat is located within the alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine. The JPH3 protein product serves to stabilize junctional membrane complexes and regulate neuronal calcium flux. We have previously demonstrated the potential pathogenic properties of JPH3 transcripts containing expanded CUG repeats. The aim of this study was to test the possibility that loss of JPH3 expression or expanded amino acid tracts also contribute to HDL2 pathogenesis.', 'Transcripts from the HDL2 locus, and their protein products, were examined in HDL2, HD, and control frontal cortex. The effect of loss of Jph3 was examined in mice with partial or complete loss of Jph3.', 'Bidirectional transcription occurs at the HDL2 locus, although expression of antisense transcripts with expanded CAG repeats is limited. Protein products with expanded amino acid tracts were not detected in HDL2 brain. However, JPH3 transcripts and full-length JPH3 protein are decreased in HDL2 brain, and Jph3 hemizygous and null mice exhibit abnormal motor function.']
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['An estimated 162,460 people will die of lung cancer in the United States in 2006, making it the leading cause of cancer deaths. Small cell lung cancer (SCLC) accounts for 20% of all lung cancers and exhibits aggressive behavior with early metastases. Current treatments yield five-year survival rates of 5 to 10%, indicating a need for novel therapeutic approaches. Histone deacetylase inhibitors (HDACIs) represent a new class of anticancer agents. Trichostatin A (TSA), an HDACI, has been shown to inhibit growth in several cancers. We hypothesized that TSA may inhibit proliferation of SCLC cells.', 'Human SCLC DMS53 cells were treated with TSA (0 to 400 nM). Light microscopy was used to assess changes in cell morphology. Western analysis was performed for acetylated histone 4 to confirm HDAC inhibition. The effect of TSA treatment on cellular growth was measured by the MTT assay. Finally, levels of BCL-2, cleaved poly(ADP-ribose) polymerase, p21, and p27 proteins were measured to look for induction of cell cycle arrest and/or apoptosis.', 'DMS53 cells treated with TSA underwent dramatic changes in cell appearance. Treated cells assumed round and spindle shapes with distinct cellular borders. Western analysis demonstrated increased levels of acetylated histone 4. TSA treatment resulted in a dose-dependent inhibition of growth. Lastly, elevated p21, p27, and cleaved poly(ADP-ribose) polymerase along with decreased BCL-2 protein levels were observed.']
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['Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS.', 'The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration.', 'Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14).']
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['Regulation of the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA) is critical in the control of fibrin deposition. While several plasminogen activators have been described, soluble plasma cofactors that stimulate fibrinolysis have not been characterized. The purpose of this study was to investigate the effects of beta(2)-glycoprotein I (beta(2)GPI), an abundant plasma glycoprotein, on tPA-mediated plasminogen activation.', 'The effect of beta(2)GPI on tPA-mediated activation of plasminogen was assessed using amidolytic assays, a fibrin gel, and plasma clots. Binding of beta(2)GPI to tPA and plasminogen was determined in parallel. The effects of IgG fractions and anti-beta(2)GPI antibodies from patients with antiphospholipid syndrome (APS) on tPA-mediated plasminogen activation were also measured.', 'Beta(2)-glycoprotein I stimulated tPA-dependent plasminogen activation in the fluid phase and within a fibrin gel. The beta(2)GPI region responsible for stimulating tPA activity was shown to be at least partly contained within beta(2)GPI domain V. In addition, beta(2)GPI bound tPA with high affinity (K(d) approximately 20 nM), stimulated tPA amidolytic activity, and caused an overall 20-fold increase in the catalytic efficiency (K(cat)/K(m)) of tPA-mediated conversion of Glu-plasminogen to plasmin. Moreover, depletion of beta(2)GPI from plasma led to diminished rates of clot lysis, with restoration of normal lysis rates following beta(2)GPI repletion. Stimulation of tPA-mediated plasminogen activity by beta(2)GPI was inhibited by monoclonal anti-beta(2)GPI antibodies as well as by anti-beta(2)GPI antibodies from patients with APS.']
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['In obesity, an increased macrophage infiltration in adipose tissue occurs, contributing to low-grade inflammation and insulin resistance. Epidermal growth factor receptor (EGFR) mediates both chemotaxis and proliferation in monocytes and macrophages. However, the role of EGFR inhibitors in this subclinical inflammation has not yet been investigated. We investigated, herein, in vivo efficacy and associated molecular mechanisms by which PD153035, an EGFR tyrosine kinase inhibitor, improved diabetes control and insulin action.', 'The effect of PD153035 was investigated on insulin sensitivity, insulin signaling, and c-Jun NH(2)-terminal kinase (JNK) and nuclear factor (NF)-kappaB activity in tissues of high-fat diet (HFD)-fed mice and also on infiltration and the activation state of adipose tissue macrophages (ATMs) in these mice.', 'PD153035 treatment for 1 day decreased the protein expression of inducible nitric oxide synthase, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in the stroma vascular fraction, suggesting that this drug reduces the M1 proinflammatory state in ATMs, as an initial effect, in turn reducing the circulating levels of TNF-alpha and IL-6, and initiating an improvement in insulin signaling and sensitivity. After 14 days of drug administration, there was a marked improvement in glucose tolerance; a reduction in insulin resistance; a reduction in macrophage infiltration in adipose tissue and in TNF-alpha, IL-6, and free fatty acids; accompanied by an improvement in insulin signaling in liver, muscle, and adipose tissue; and also a decrease in insulin receptor substrate-1 Ser(307) phosphorylation in JNK and inhibitor of NF-kappaB kinase (IKKbeta) activation in these tissues.']
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['Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort.', 'Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models.', 'Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors.']
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['The effect of inhaled nitric oxide (NO) treatment on pulmonary function in the setting of adult respiratory distress syndrome is controversial. We examined the effect of inhaled NO on pulmonary function in an isolated rabbit lung model of oleic acid (OA)-induced acute lung injury. We hypothesized that NO would decrease pulmonary artery pressure and improve oxygenation.', 'Rabbit heart-lung blocks were isolated, flushed in vivo, harvested, and immediately perfused with whole blood and ventilated with 50% oxygen (O2). Pulmonary artery pressure was determined every 15 seconds for 60 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, and 60 minutes after initiation of OA infusion. Rabbits were randomized into four study groups: saline control; OA control, which received a 20-minute infusion of 50% OA/ethanol solution; NO treatment (20 ppm NO inhaled before OA infusion); and NO control, which underwent NO (20 ppm) pretreatment, followed by saline infusion. Pulmonary artery pressure, oxygenation (arteriovenous O2 difference), compliance, and wet/dry lung weight were determined.', 'Pretreatment with NO caused significant increases in pulmonary artery pressure (NO treatment versus NO control and saline control; no significant difference between NO treatment group and OA control group), and did not improve oxygenation in our model.']
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['Important candidate genes involved in the ovarian response to exogenous FSH are the estrogen receptor genes (ESRs), since the effects of estrogens on follicle growth, maturation and oocyte release. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A\u2009+\u20091730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF).', 'A cross-sectional study was performed involving 136 infertile women less than 39\xa0years of age with normal ovarian reserve. Patients were divided according to the same COH protocol for statistical analysis. The Taqman assay was used for PvuII and XbaI of ESR1, and RsaI and AluI of ESR2 genotyping. Serum estradiol and FSH were measured by Elisa assay.', 'The PvuII (ESR1) TT and RsaI (ESR2) GG genotypes were associated with a longer induction period and higher doses of medication (p\u2009<\u20090.03). The XbaI (ESR1) AA genotype was associated with better COH results, including a larger number of follicles, mature oocytes, embryos, and good quality embryos (p\u2009<\u20090.05). The AluI GG genotype showed an association with the Ovarian Hyperstimulation Syndrome (OHSS) (p\u2009=\u20090.03). According to the haplotype analysis of ER1 (PvuII/XbaI), we demonstrated that the CA combination increases by 0.68 the number of good quality embryos while the TG decreases it by 0.71 (p\u2009=\u20090.04).']
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['The disproportionate distribution of arable land and water resources has become a bottleneck for guaranteeing food security in China. Virtual water and virtual water trade theory have provided a potential solution to improve water resources management in agriculture and alleviate water crises in water-scarce regions. The present study evaluates the green and blue virtual water content of wheat, maize and rice at the regional scale in China. It then assesses the water-saving benefits of virtual water flows related to the transfer of the three crops between regions.', 'The national average virtual water content of wheat, maize and rice were 1071 m(3) per ton (50.98% green water, 49.02% blue water ), 830 m(3) per ton (76.27% green water, 23.73% blue water) and 1294 m(3) per ton (61.90% green water, 38.10% blue water), respectively. With the regional transfer of wheat, maize and rice, virtual water flows reached 30.08 Gm(3) (59.91% green water, 40.09% blue water). Meanwhile, China saved 11.47 Gm(3) green water, while it consumed 7.84 Gm(3) more blue water than with a no-grain transfer scenario in 2009.']
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['Achieving symmetry is a key goal in breast reconstruction. Anatomically shaped tabbed expanders are a new tool in the armamentarium of the breast reconstruction surgeon. Suture tabs allow for full control over the expander position and thus inframammary fold position, and, in theory, tabbed expanders mitigate many factors responsible for poor symmetry. The impact of a tabbed expander on breast symmetry, however, has not been formally reported. This study aims to evaluate breast symmetry following expander-implant reconstruction using tabbed and non-tabbed tissue expanders.', 'A chart review was performed of 188 consecutive expander-implant reconstructions that met the inclusion criteria of adequate follow-up data and postoperative photographs. Demographic, oncologic, postoperative complication, and photographic data was obtained for each patient. The photographic data was scored using a 4-point scale assessing breast symmetry by three blinded, independent reviewers.', 'Of the 188 patients, 74 underwent reconstruction with tabbed expanders and 114 with non-tabbed expanders. The tabbed cohort had significantly higher symmetry scores than the non-tabbed cohort (2.82/4±0.86 vs. 2.55/4±0.92, P=0.034).']
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['In preterm infants, a decreased immunological response and lower serological effectiveness are observed after immunizations due to ineffectiveness of both humoral and cellular immune mechanisms.', 'To determine the effect of 80% neutral oligosaccharides [small-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (scGOS/lcFOS)] in combination with 20% pectin-derived acidic oligosaccharides (pAOS) on antibody concentrations after DTaP-IPV-Hib immunization in preterm infants.', 'In this randomized clinical trial, preterm infants with gestational age <32 weeks and/or birth weight <1500 g received enteral supplementation with scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Blood samples were collected at 5 and 12 months of age.', 'In total, 113 infants were included. Baseline and nutritional characteristics were not different in both groups. Geometric mean titers were not different after prebiotic supplementation at 5 months, Ptx (37/44 EU/ml), FHA (78/96 EU/ml), Prn (78/80 EU/ml), Diphtheria (0.40/0.57 IU/ml), Tetanus (0.74/0.99 IU/ml) and Hib (0.35/0.63 µg/ml), and at 12 months Ptx (55/66 EU/ml), FHA (122/119 EU/ml), Prn (116/106 Eu/ml), Diphtheria (0.88/1.11 IU/ml), Tetanus (1.64/1.79 IU/ml) and Hib (2.91/2.55 µg/ml).']
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['Casticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear.', "Apoptotic activities of casticin (1.0 µmol/l) and TRAIL (25, 50 ng/ml) alone or in combination in the gastric cancer cell lines BGC-823, SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection kit, flow cytometry (FCM) with propidium iodide (PI) staining and activities of caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP) protein using western blot analysis. Death receptors (DR) expression levels were evaluated using FCM analysis and western blotting. 2', 7'-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to measure the increase in reactive oxygen species (ROS) levels in cells. Multiple interventions, such as siRNA transfection and pharmacological inhibitors were used to explore the mechanisms of these actions.", 'Subtoxic concentrations of casticin significantly potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC-803 cells. Casticin dramatically upregulated DR5 receptor expression but had no effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing of the CCAAT/enhancer binding protein homologous protein (CHOP) and pretreatment with salubrinal, an endoplasmic reticulum (ER) stress inhibitor, attenuated casticin-induced DR5 receptor expression, and apoptosis and ROS production. Casticin downregulated the expression levels of the cell survival proteins cFLIP, Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803).']
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['Unresolved inflammation and tissue destruction are underlying mechanisms of periodontitis, which is linked to dysregulated polymorphonuclear neutrophil (PMN) functions. Lipoxin A4 (LXA4) is a specialized proresolving lipid mediator (SPM) that dampens excessive inflammation, promotes resolution, and protects from leukocyte-mediated tissue damage. Human periodontal ligament stem cells (hPDLSCs) represent key players during tissue regeneration and may contribute to resolution of inflammation; thus, they may represent a promising tool in regenerative dentistry. In the present study, we investigated the actions of hPDLSCs on PMN apoptosis and antimicrobial functions, and determined the impact of LXA4 on hPDLSCs. hPDLSCs significantly reduced apoptosis and stimulated microbicidal activity of human PMNs, via both cell-cell interactions and paracrine mechanisms. Lipid mediator metabololipidomics analysis demonstrated that hPDLSCs biosynthesize SPMs, including resolvin D1, D2, D5, and D6; protectin D1; maresins; and LXB4; as well as prostaglandins D2, E2, and F2α. LXA4 significantly enhanced proliferation, migration, and wound healing capacity of hPDLSCs through the activation of its cognate receptor ALX/FPR2, expressed on hPDLSCs. Together, these results demonstrate that hPDLSCs modulate PMN functions, and provide the first evidence that stem cells generate SPM and that the LXA4-ALX/FPR2 axis regulates regenerative functions of hPDLSCs by a novel receptor-mediated mechanism.']
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['Positive expiratory pressure (PEP) has been used to promote airway clearance in individuals with chronic obstructive pulmonary disease (COPD) for many years; however, its mechanism of action and benefits are unclear. Previous authors have suggested that PEP improves collateral ventilation via changes in lung volumes.', 'It was the aim of this study to determine whether PEP improves ventilation inhomogeneity more than controlled huffing and coughing in individuals with stable COPD.', 'Twelve participants with COPD (mean forced expiratory volume in 1 s 45% predicted) and chronic sputum expectoration performed PEP therapy (10-20 cm H2O) or controlled huffing and coughing in random order on alternate study days with a 48-hour washout. Measures of acinar and conductive airway ventilation (S(acin), S(cond)), lung volumes, spirometry and sputum wet weight were recorded before, immediately after and 90 min following treatment. Ease of expectoration [visual analogue scale (VAS)] and oxyhaemoglobin saturation were assessed immediately following treatment.', 'There were no significant differences between the effect of either test condition at any time point for any test parameter. Mean Sacin immediately following PEP and control conditions was 0.465 and 0.438 litre(-1), respectively (p = 0.45 for comparison between conditions) and mean S(cond) was 0.042 and 0.039 litre(-1) (p = 0.55). PEP therapy did not significantly enhance total mean sputum expectoration compared to controlled huffing and coughing (7.06 vs. 6.15 g; p = 0.51) and did not improve ease of expectoration (VAS PEP 4.8 cm vs. control 4.1 cm; p = 0.53).']
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['Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis.', 'As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to (11)C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm(3) and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE.', 'After SE, increases in (11)C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques.']
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['Sessile serrated polyps are precursors of colorectal cancer arising from molecular pathways distinct from conventional adenomas. The association between sessile serrated polyps and conventional adenomas is not well known.', 'We hypothesize that individuals who have coexistent sessile serrated polyps and conventional adenomas express a more severe phenotype than those harboring lesions from only one pathway. We compare colorectal phenotypes among individuals with sessile serrated polyps, those with conventional adenomas, and those expressing both.', 'This investigation is a retrospective cross-sectional study of 3 cohorts.', 'This study was conducted in multiple centers within 1 health care system.', 'Individuals with sessile serrated polyps and/or conventional adenomas on first lifetime colonoscopy were included in the study.', 'The demographics and polyp characteristics were compared among 3 cohorts to determine the differences in phenotypic expression.', 'Two hundred sixty individuals with sessile serrated polyps and 173 with only conventional adenomas were included. The disease phenotype was most severe in individuals with coexistent sessile serrated polyps and adenomas. The sessile serrated polyps in this cohort were larger (P = .01) than in the serrated-only cohort. The conventional adenomas in this cohort were more numerous (P = .035) and more advanced (P = .046) than in the adenoma-only cohort. Synchronous colorectal cancers were found exclusively in the cohorts with sessile serrated polyps, although this did not reach statistical significance (P = .06).']
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["Two studies have reported that abnormal colour vision is under-represented among cricketers, presumably because cricketers with abnormal colour vision have difficulty seeing the red ball against the green grass of the cricket field and the green foliage around it. We have previously reported on the difficulties of five cricketers with abnormal colour vision but we have also reported that one of Australia's finest cricketers was a protanope. This survey was undertaken to confirm the under-representation of abnormal colour vision among cricketers and to ascertain whether those playing tend to be (1) those with a mild colour vision deficiency, (2) bowlers rather than batsman and (3) prefer to field close to the batsman rather than in the outfield.", 'The colour vision of 293 members of seven Melbourne Premier cricket clubs was tested using the Ishihara test. Those who failed were examined further to confirm their abnormal colour vision, to assess its severity with the Farnsworth D15 test and to classify it as either protan or deutan using the Medmont C100 test. A questionnaire about cricketing ability and problems playing cricket was administered.', 'Twenty-six (8.9 per cent) of the cricketers had abnormal colour vision, of whom six played in the First Grade (6.7 per cent of First Grade players). The proportion of cricketers with a severe deficiency was significantly less than expected for the First Grade players. There were only two protans. Bowlers were not over-represented among the colour vision defective cricketers but those preferring to field close to the batsman were significantly over-represented.']
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['Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated.', 'To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.', 'Human, murine and in vitro primary alveolar epithelial cell work were included in this study.', 'Vitamin D deficiency (plasma 25(OH)D levels <50\u2005nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients.']
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['An IM combination of meperidine, promethazine, and chlorpromazine (DPT) has been given as sedation for pediatric procedures for more than 40 years. We compared this IM combination to oral (PO) ketamine/midazolam in children having cardiac catheterization. A total of 51 children, ages 9 mo to 10 yr, were enrolled and randomized in this double-blinded study. All children received an IM injection at time zero and PO fluid 15 minutes later. We observed acceptance of medication, onset of sedation and sleep, and sedative efficacy. The cardiorespiratory changes were evaluated. Sedation was supplemented with IV propofol as required. Recovery time, parental satisfaction, and patient amnesia were assessed. Ketamine/midazolam given PO was better tolerated (P < 0.0005), had more rapid onset (P < 0.001), and provided superior sedation (P < 0.005). Respiratory rate decreased after IM DPT only. Heart rate and shortening fraction were stable. Oxygen saturation and mean blood pressure decreased minimally in both groups. Supplemental propofol was more frequently required (P < or = 0.02) and in larger doses (P < 0.05) after IM DPT. Parental satisfaction ratings were higher (P < 0.005) and amnesia was more reliably obtained (P = 0.007) with PO ketamine/midazolam. Two patients needed airway support after the PO medication, as did two other patients when PO ketamine/midazolam was supplemented with IV propofol. Although PO ketamine/midazolam provided superior sedation and amnesia compared to IM DPT, this regimen may require the supervision of an anesthesiologist for safe use.']
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['It is widely believed that younger prostate cancer patients are at greater risk of recurrence following radiotherapy (RT).', 'From 1992 to 2007, 2168 (395 age ≤ 60) men received conformal RT alone for prostate cancer at our institution (median dose=76 Gy, range: 72-80). Multivariable analysis (MVA) was used to identify significant predictors for BF and PCSM. Cumulative incidence was estimated using the competing risk method (Fine and Gray) for BF (Phoenix definition) and PCSM to account for the competing risk of death.', 'With a median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age ≤ 60 vs. 23.7% for age >60 (p=0.29). Eight-year PCSM was 3.0% for age ≤ 60 vs. 2.0% for age >60 (p=0.52). MVA for BF identified initial PSA [adjusted HR=1.7 (PSA 10-20), 2.6 (PSA >20), p<0.01], Gleason score [adjusted HR=2.1 (G7), 1.9 (G8-10), p<0.01], T-stage [adjusted HR=1.7 (T2b-c), 2.6 (T3-4), p<0.01], and initial androgen deprivation therapy (ADT) [adjusted HR=0.38 (ADT >12 months), p<0.01] as significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score [adjusted HR=3.0 (G8-10), p=0.01] and T-stage [adjusted HR=8.7 (T3-4), p<0.01] as significant, but not age, PSA, or ADT.']
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['Long-term renal transplant function is limited primarily by a progressive scarring process loosely termed "chronic rejection, chronic allograft nephropathy, or allograft fibrosis." Although the etiology of transplant fibrosis is uncertain, several possible factors including chronic cyclosporin A (CsA) exposure may contribute to its pathogenesis. CsA stimulates renal fibrosis perhaps through the induction of the potent pro-sclerotic growth factor, transforming growth factor beta (TGFbeta). Previously, we demonstrated that, in human transplant biopsies, acute CsA toxicity but not acute tubular necrosis is associated with elevated levels of renal TGFbeta protein. We now examine whether long-term CsA treatment (>1 year) is associated with elevated levels of intra-allograft TGFbeta and whether heightened expression of TGFbeta is clinically significant.', 'Using immunohistochemical techniques, we determined the relative level of expression of intrarenal TGFbeta protein in transplant biopsies. We studied biopsies obtained from 40 CsA-treated patients that were diagnosed as having chronic allograft fibrosis. Biopsies were scored as having minimal or high levels of TGFbeta.', 'Seventy-two percent of patients expressed high levels of intra-allograft TGFbeta. This group of patients lost renal function at an average rate of -19.5+/-17.3 ml/min/year. In contrast, patients with minimal or no TGFbeta expression experienced a decline of only -6.2+/-4.1 ml/min/year (P=0.01).']
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['We recently described a decreased lymphocyte-mediated cytotoxicity to autologous endometrium and to natural killer-sensitive targets in women with endometriosis. The purpose of the present study was to investigate whether the defect remained after CO2-laser excision of the endometriotic lesions.', 'In 15 women with endometriosis the cytotoxicity assays were performed before and three to four months after complete removal of the endometriotic lesions with CO2-laser excision. CA-125 serum levels were measured before and after laser laparoscopy, in order to confirm that endometriosis had been treated properly.', "After removal of the endometriotic lesions the decreased natural killer activity (K562-assay) and the impaired cytotoxicity of autologous and even heterologous lymphocytes to the endometrium remained unchanged, and those cytotoxicity assays were still significantly decreased compared to the women without endometriosis. CA-125 serum concentrations, however, were still significantly decreased three to four months after CO2-laser excision of the endometriosis. (paired Student's t-test p < 0.007)."]
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['Low infliximab (IFX) trough levels and high anti-infliximab antibodies (ATI) levels are associated with loss of response to IFX. Optimizing IFX levels to maintain target concentrations before loss of response may improve long-term efficacy. We hypothesized that trough levels at week 14 are predictive of IFX durability.', 'A prospective observational cohort of pediatric patients with inflammatory bowel disease initiating IFX had IFX and ATI levels drawn at weeks 14 and 54. Primary outcome was week 54 persistent remission (PR), defined as clinical remission without IFX dose intensification. Univariate analyses tested associations of week 14 IFX (IFX14) and ATI (ATI14) levels, clinical and laboratory data with week 54 outcomes. Receiver operating curve analysis and positive and negative predictive values for IFX14 cut-off points were examined.', 'Of 58 patients enrolled, 8 (13%) stopped IFX before week 14 and 4 discontinued IFX between weeks 14 and 54. IFX14 level (P = 0.03), baseline C-reactive protein (CRP) level (P = 0.01), and week 14 CRP (CRP14) level (P = 0.0001) were associated with PR. A model with IFX14 levels predicting PR had an area under the receiver operating curve of 0.68 and a model with both IFX14 level and CRP14 >1.0 mg/dL had an area under the receiver operating curve of 0.74. IFX14 cut points of >3, >4, and >7 µg/mL had positive predictive values of 64%, 76% and 100%, respectively, for predicting PR.']
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['To determine the prevalence of American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) classification criteria among systemic lupus erythematosus (SLE) patients; to determine disease activity and severity; and to investigate the correlation of classification criteria with disease activity, and of disease activity and damage index with disease duration.', 'We performed a cross-sectional study on 110 SLE patients from the Division of Rheumatology and Clinical Immunology, University Hospital Centre Rijeka, Croatia in the period from September to December 2013 and determined disease duration and the total number of ACR and SLICC classification criteria. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) index and organ damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.', 'The number of SLICC classification criteria met per patient was significantly higher than the number of ACR criteria (7 [IQR 6-8] vs 5 [IQR 4-6], P < 0.001). Moderate correlations were detected between the number of SLICC classification criteria and disease activity index, both in case of active (r=0.48, P=0.003) and inactive disease (r=0.43, P < 0.001). We neither found a correlation between the number of ACR criteria and disease activity nor between disease activity and disease duration. However, there was a good correlation between SLICC/ACR damage index and disease duration (r=0.63, P < 0.001).']
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['To investigate the effect of Src kinase inhibitor PP2 on intercellular communication of gap junction in breast cancer cells.', 'Cultured breast cancer Hs578T cells were treated with various concentrations of pp2 (0,1,2,4,8,16,32 μmol/L) for 24h. Cell growth was determined by MTT assay; dye spread in Hs578T cells was measured by Parachute assay; and the expression of Src kinase in Hs578T cells was detected by Western blot.', 'MTT assay showed that the survive rate of Hs578T cells treated with PP2 (1 ≊ 8 μmol/L) was 98% ± 3% ≊ 94 % ± 4%. Parachute assay showed that compared to control group the standard normalized dye spread rates of Hs578T cells treated with 1,2,4 and 8 μmol/L PP2 were 1.60 ± 0.08,2.00 ± 0.05,2.20 ± 0.05 and 2.70 ± 0.09,respectively (all P<0.01). Moreover,compared to control group at the same time points,the standard normalized dye spread of Hs578T cells treated with 8 μmol/L PP2 for 6,12 and 24 h were 1.4 ± 0.05,1.7 ± 0.06,and 2.2 ± 0.07,respectively (all P<0.01). Western blot showed that the expression ratios of Src kinase/β-actin of Hs578T cells treated with 1,2,4 and 8 μmol/L PP2 for 24 h were 0.93 ± 0.02,0.70 ± 0.09,0.66 ± 0.09 and 0.36 ± 0.10,which were significantly inhibited compared with control group (P<0.05 or 0.01). And the expression ratio of Src kinase/β-actin of Hs578T cells treated with 8 μmol/L PP2 for 6,12 and 24h was 0.82 ± 0.03,0.66 ± 0.08 and 0.59 ±0.09, which were all inhibited significantly compared to control group (P<0.01).']
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['Immobilization and space flight are causes of disuse osteoporosis. Increasing calcium intake may counteract this disuse-induced bone loss.', 'We conducted two bedrest experiments (crossover design: bedrest versus ambulatory control) in a metabolic ward, studying the effect of 1000 mg/d of calcium intake (study A, length of intervention 14 d) compared with that of a high calcium intake of 2000 mg/d (study B, 6 d) on markers of bone turnover. Both studies were randomized, controlled studies with the subjects staying under well-controlled environmental conditions (study A, 9 male subjects, age 23.6+/-3.0 y; study B, 8 male subjects, age 25.5+/-2.9 y). Blood was drawn to analyze serum calcium, parathyroid hormone, procollagen type I C-terminal propeptide, and bone alkaline phosphatase. Urine (24-h) was collected for analysis of calcium, C-terminal telopeptide of collagen type I, and N-terminal telopeptide of collagen type I.', 'In both studies, serum calcium levels remained unchanged. Procollagen type I C-terminal propeptide was lower (P=0.03) in the bedrest phase than in the ambulatory phase in study A and tended to be lower (P=0.08) in bedrest in study B, whereas bone alkaline phosphatase was not affected in either study. Urinary calcium excretion was greater during bedrest than during the ambulatory phase (study A, P=0.005; study B, P=0.002). C-terminal telopeptide of collagen type I excretion was also greater during bedrest in both studies (study A, P<0.001; study B, P<0.001).']
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['Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats.', 'Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out.', 'Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL.']
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['Assessment of whether admission plasma troponin I level is associated with mortality or requirement for vasoactive drugs in pediatric intensive care.', 'Retrospective cohort study.', 'Single centre, tertiary referral general PICU, without a cardiac surgical program.', 'Three hundred and nineteen patients 0-18 years old in two cohorts. Cohort 1 was admitted between January 2009 and September 2012 and the cohort 2 between April 2014 and April 2015.', 'None.', 'Plasma troponin I was measured in patients in cohort 1 only if the attending physician ordered the test due to clinical concern regarding myocardial injury. The second cohort had plasma troponin I routinely measured at admission. The primary outcome was death during PICU admission, and the secondary outcome was maximum inotrope requirement during PICU stay, measured by Vasoactive Inotrope Score. Plasma troponin I was a discriminator for mortality in both cohorts (area under the receiver-operating characteristic curve of 0.73 and 0.86 in cohorts 1 and 2, respectively). In an adjusted analysis using Cox regression, accounting for Pediatric Index of Mortality 2 risk of mortality and age, elevated plasma troponin I was significantly associated with death in both cohorts (hazard ratio, 4.99; p = 0.033; hazard ratio, 10.5; p = 0.026 in cohorts 1 and 2, respectively). Elevated plasma troponin I was only associated with increased Vasoactive Inotrope Score following multivariate analysis in the cohort 2.']
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['BACKGROUND, & AIMS: Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes.', 'We performed a cross-sectional study using the United Kingdom-PBC, patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures).', "Seventy-nine percent of the patients reported current UDCA, therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response rate; P < .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P < .0001). Patients who presented at younger ages also were significantly more likely not to respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's (P < .0001). The increase in fatigue severity in women was related strongly (r = 0.58; P < .0001) to higher levels of autonomic symptoms (P < .0001)."]
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['To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1 (PLK1) in colon cancer.', 'Expression of PLK1 was investigated by immunohistochemistry (158 cases) and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1 expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated.', 'Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1. Overexpression of PLK1 correlated positively with Dukes stage (P<0.001), tumor stage (P = 0.001) and nodal status (P<0.05). Additionally, PLK1 expression was a prognostic marker in univariate survival analysis (P<0.01) and had independent prognostic significance (RR = 3.3, P = 0.02) in patients with locoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67 expression.']
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['Cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (CBF), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the CBF increase that accompanies increases in PaCO2 in sleep, particularly in REM sleep when CBF is high.', 'Newborn lambs (n = 5) were instrumented to record CBF, arterial pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of hypercapnia (FICO2 = 0.08) during spontaneous sleep-wake states before (intact) and after sympathectomy (bilateral superior cervical ganglionectomy).', 'During hypercapnia in intact animals, CBF increased and CVR decreased in all sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% +/- 6.1%, CVR -26.9% +/- 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5% +/- 3.6%) and CVR decreases (-21.8% +/- 2.1%) during REM were less (P < 0.05). However the maximal CBF (27.8 +/- 4.2 mL/min) and minimum CVR (1.8 +/- 0.3 mm Hg/ min/mL) reached during hypercapnia were similar to intact values.']
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['Recent evidence suggests that angiotensin II (Ang II) induces a variety of proinflammatory mediators including chemokines. Nuclear factor-kappaB (NF-kappaB) activation plays an important role in Ang II-mediated inflammation. The present study investigated which Ang II receptor subtype is involved in NF-kappaB activation. We focused particularly on the Ang II subtype 2 (AT2) receptor because we previously observed that Ang II-induction of the chemokine RANTES in vitro and in vivo is mediated through AT2 receptors.', 'AT1 or AT2 receptors were selectively overexpressed in COS7 cells that normally do not express Ang II receptors. In addition, rat glomerular endothelial cells (GER) that express AT1 and AT2 receptors and PC12 cells that exclusively exhibit AT2 receptors were studied also. Ang II-receptor expression was confirmed by Western blots of membrane lysates. NF-kappaB DNA binding in vitro was detected by electrophoretic shift assays. In addition, in vivo transactivation of a reporter gene construct with kappa enhancer coupled to luciferase also was investigated. Expression of the inhibitor of kappaB alpha (IkappaB-alpha) was detected by Western blots.', 'In AT1 or AT2 receptor transfected cells, but not untransfected COS7 cells, 10-7 mol/L Ang II induced NF-kappaB DNA binding in vitro, as detected by electrophoretic shift assays and in vivo transactivation of a reporter gene construct. The AT2 receptor antagonist PD 123319 but not losartan attenuated Ang II-mediated NF-kappaB activation in COS7 cells transfected with AT2 receptors. While Ang II also induced NF-kappaB activation in PC12 cells, this activation was blocked by PD 123319. Finally, stimulation of GERs with Ang II led to the activation of NF-kappaB through both subtypes of Ang II receptors. Nuclear extracts from COS7 cells transfected with AT2 receptors and PC12 cells with NF-kappaB DNA-binding activity consisted of p50/p65 complexes. There was no difference in subunit composition of nuclear proteins from Ang II-stimulated AT1 receptor transfected COS7 cells. An artificial peptide (p-Amino-Phe6-Ang II) with a high affinity for the AT2 receptor also activated NF-kappaB. Ang II-induced activation of NF-kappaB was associated with degradation of IkappaB-alpha in all studied cell lines.']
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['Acute vision loss from optic neuritis typically resolves; however, recovery is often not complete. Permanent vision loss from retinal ganglion cell (RGC) death occurs in 40% to 60% of patients. Current therapy (high-dose corticosteroids) speeds recovery but does not change final visual outcomes. Here the authors examined whether corticosteroids administered early in the disease course can prevent RGC loss in experimental optic neuritis.', 'RGCs were retrogradely labeled with fluorogold in SJL/J mice. Experimental autoimmune encephalomyelitis (EAE) was induced by immunization with proteolipid protein peptide. Optic neuritis began 9 days after immunization. Mice were treated daily with dexamethasone, methylprednisolone, or PBS from days 0 to 14 or days 10 to 14 and then were killed on day 14, 18, or 22.', 'Corticosteroid treatment initiated before optic neuritis onset (days 0-14) suppressed EAE and reduced optic neuritis incidence through day 14. In the few eyes that developed optic neuritis, inflammation was mild, and RGC loss was attenuated. After treatment was stopped on day 14, mice rapidly developed EAE and optic neuritis by day 18, but RGC loss was still reduced. By day 22, RGC loss increased to levels similar to those of untreated optic neuritis eyes. Corticosteroid treatment after optic neuritis onset (days 10-14) slowed EAE progression and showed a trend toward suppression of optic neuritis and RGC loss on day 14 that was lost by day 18.']
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['Trans-11 vaccenic acid (VA) is a fatty acid produced by ruminants entering the human food supply through meat and dairy products, which appears not to have the health risks associated with industrially produced trans-fatty acids. In this study, we investigated the effect of VA on insulin secretion in vivo in rats and in vitro in human and rat islets after diabetogenic insult.', 'Hyperglycemic clamp showed that VA dietary supplementation for 8 weeks significantly increased glucose turnover in rats with type 2 diabetes (T2D), accompanied by an elevated plasma C-peptide concentration, indicating improved insulin secretion. The β-cell area and proliferation rate were higher in T2D+VA than T2D group. Isolated islets from T2D+VA rats had higher glucose-stimulated insulin secretion (GSIS) than T2D group. In vitro, VA treatment for 24 and 48 h significantly enhanced GSIS in rat and human islets after diabetogenic challenges. The mRNA expression of G-protein-coupled receptor 40 (GPR40) and regenerating islet-derived 1α (REG-1α) were consistently increased by VA in both rat and human islets.']
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['High levels of the antimicrobial peptide, LL-37, are detected in gingival crevicular fluid from patients with chronic periodontitis. LL-37 not only shows antimicrobial activity but also affects host-cell viability. The objective of the present study was to identify endogenous mechanisms that antagonize the detrimental effects of LL-37 on osteoblast viability, focusing on the human peptide p33 expressed on the surface of various cell types.', 'Human osteoblast-like MG63 cells and human hFOB1.19 osteoblasts were treated with or without LL-37 in the presence or absence of p33. Recombinant human p33 was expressed in an Escherichia coli expression system. Lactate dehydrogenase (LDH) was assessed using an enzymatic spectrophotometric assay. DNA synthesis was determined by measuring [(3) H]-thymidine incorporation. Cell number was assessed by counting cells in a Bürker chamber. Intracellular Ca(2+) was monitored by recording Fluo 4-AM fluorescence using a laser scanning confocal microscope. Cellular expression of p33 was determined by western blotting.', 'LL-37 caused a concentration-dependent release of LDH from human osteoblasts, showing a half-maximal response value (EC50 ) of 4\xa0μm and a rapid and sustained rise in the intracellular Ca(2+) concentration of osteoblasts, suggesting that LL-37 forms pores in the cell membrane. p33 (10\xa0μm) inhibited the LL-37-induced LDH release and LL-37-evoked rise in intracellular Ca(2+) concentration, suggesting that p33 prevents LL-37-induced permeabilization of the cell membrane. Moreover, p33 blocked LL-37-induced attenuation of osteoblast numbers. Also, mucin antagonized, at concentrations representative for nonstimulated whole saliva, LL-37-evoked LDH release, whilst cationic endogenous polyamines had no impact on LL-37-induced LDH release from osteoblasts.']
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['Cytomegalovirus (CMV) and BK virus (BKV) infections can cause significant morbidity after kidney and kidney-pancreas transplant. There are limited data on the epidemiology and interactions between these two viral pathogens.', 'We prospectively screened 609 kidney or kidney-pancreas transplant recipients from January 2007 to June 2011 for BKV and/or CMV viremia. This included 7453 quantitative BKV polymerase chain reaction and 15,496 quantitative CMV polymerase chain reaction tests. We evaluated risk factors and timing of these infections and the impact of treatment of one infection on the other.', 'Among 609 recipients, 108 (17.7%) developed CMV viremia, of which 95 (88%) were asymptomatic, 5 (5%) had CMV syndrome, and 8 (7%) developed CMV tissue invasive disease at a median of 5.6 months after transplantation. Risk factors for CMV infection using multivariable analysis were D+R- serogroup (P≤0.0001), donor age >50 years (P=0.013), and higher mean tacrolimus (P=0.0009) and mycophenolate mofetil (P=0.01) blood levels. The incidence of BKV infection in the total population was 163 of 609 (26.7%), of which 150 (92%) occurred in patents without antecedent CMV viremia. Such patients demonstrated a higher rate of subsequent BKV viremia than patients with antecedent CMV viremia (P=0.003; hazard ratio, 2.05; 95% confidence interval, 1.2-3.4). Moreover, we found that only symptomatic CMV viremia had a significant negative impact on graft survival when compared with asymptomatic CMV viremia and those without CMV viremia (relative risk, 3.5; 95% confidence interval, 1.06-8.9; P=0.04).']
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['During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K(ATP)) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC.', 'Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K(ATP) channel opener, nicorandil (25 microg. kg(-1). min(-1) IV), decreased dNE at 40 minutes of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine.']
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['We investigated whether remote organ preconditioning (RPC) can preserve pulmonary function following repeated myocardial ischemia/reperfusion in a model mimicking multi-vessel off-pump coronary artery bypass (OPCAB) revascularization.', 'Nine sheep (Group-RPC) underwent RPC by three episodes of five-minute occlusion and five-minute reperfusion of the iliac artery. Five sheep (Group-C) were time-matched controls. Afterwards, ten-minute occlusion and reperfusion of the left anterior descending, the first diagonal and the left circumflex coronary arteries were performed consecutively. Hemodynamic and respiratory parameters and arterial blood gases were measured until 120 min after the final coronary reperfusion. Anesthesia was maintained with halothane in oxygen and nitrous oxide. Animals were ventilated with a tidal volume of 15-20 mL.kg(-1) in a non-rebreathing system, and a respiratory rate 14-16 min, with 5-cm H(2)O positive end expiratory pressure after thoracotomy.', 'Repeated coronary occlusion and reperfusion was associated in this experimental model with an increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) and a decrease in PaO(2) and PaO(2)/FIO(2) in Group-C. After 120 min reperfusion, PaO(2) and PaO(2)/FIO(2) in Group-RPC were higher (192 +/- 69 mmHg and 241 +/- 78 vs 115 +/- 54 mmHg and 129 +/- 64, P < 0.05), while PVR and PAP were lower than in Group-C. At 120 min of reperfusion, PaO(2) and PaO(2)/FIO(2) were inversely correlated with PVR (P < 0.01).']
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['Carvedilol is a beta-adrenoceptor blocker with a vasodilatory action that is more effective for the treatment of congestive heart failure than other beta-blockers. Recently, carvedilol has been reported to reduce oxidative stress, which may consequently reduce the deactivation of adenosine-producing enzymes and increase cardiac adenosine levels. Therefore, carvedilol may also have a protective effect on ischemia and reperfusion injury, because adenosine mediates cardioprotection in ischemic hearts.', "In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Carvedilol reduced the infarct size (15.0+/-2.8% versus 40.9+/-4.2% in controls), and this effect was completely reversed by the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (45.2+/-5.4%) or by an inhibitor of ecto-5'-nucleotidase (44.4+/-3.6%). There were no differences of either area at risk or collateral flow among the various groups. When the coronary perfusion pressure was reduced in other dogs so that coronary blood flow was decreased to 50% of the nonischemic level, carvedilol increased coronary blood flow (49.4+/-5.6 to 73.5+/-7.5 mL x 100 g(-1) x min(-1); P<0.05) and adenosine release (112.3+/-22.2 to 240.6+/-57.1 nmol/L; P<0.05) during coronary hypoperfusion. This increase of coronary blood flow was attenuated by either 8-sulfophenyltheophylline or superoxide dismutase. In human umbilical vein endothelial cells cultured with or without xanthine and xanthine oxidase, carvedilol caused an increase of ecto-5'-nucleotidase activity."]
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['Lumbar spinal stenosis is a common cause of back and leg pain with the most severe cases treated surgically. Regarding the surgery outcome, the importance of early postoperative depression and pain is unknown.', 'To examine whether the coexistence of pain and depressive symptoms on 3-month follow-up predicts the 2-year surgery outcome.', '93 patients (mean age 62 years) with symptomatic lumbar spinal stenosis underwent decompressive surgery. They completed the same set of questionnaires, 3 months, 1 year and 2 years postoperatively. Depression was assessed with the 21-item Beck Depression Inventory (BDI). Physical functioning and pain were assessed with the Oswestry Disability Index, the Stucki Questionnaire, self-reported walking ability, the visual analogue scale (VAS) and pain drawing. Comparisons were made between groups according to the "misery" (i.e. the coexistence of elevated pain and depression on 3-month follow-up) status. Logistic regression analysis was used to examine the factors independently associated with a poor surgery outcome on 2-year follow-up.', 'The patients in the misery group (n=24) showed greater symptom severity and greater disability than the patients in the non-misery group (n=69) at all follow-up stages. No clinical improvement was seen in the misery group during the follow-up. An independent association was observed between belonging to the misery group and 2-year disability, symptom severity and poor walking capacity.']
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['There is a growing population of adults with repaired cyanotic congenital heart disease. These patients have increased risk of impaired cardiac health and premature death. We hypothesized that hypoxia in early life before surgical intervention causes lasting changes in left ventricular structure and function with physiological implications in later life.', 'Sprague-Dawley rats reared initially hypoxic conditions (FiO(2)=0.12) for days 1-10 of life were compared to rats reared only in ambient air. Cellular morphology and viability were compared among LV cardiomyocytes and histological analyses were performed on LV myocardium and arterioles. Intracellular calcium transients and cell shortening were measured in freshly-isolated cardiomyocytes, and mitochondrial hexokinase 2 (HK2) expression and activity were determined. Transthoracic echocardiography was used to assess LV function in anesthetized animals.', 'Cardiomyocytes from adult animals following hypoxia in early life had greater cellular volumes but significantly reduced viability. Echocardiographic analyses revealed LV hypertrophy and diastolic dysfunction, and alterations in cardiomyocyte calcium transients and cell shortening suggested impaired diastolic calcium reuptake. Histological analyses revealed significantly greater intima-media thickness and decreased lumen area in LV arterioles from hypoxic animals. Alterations in mitochondrial HK2 protein distribution and activity were also observed which may contribute to cardiomyocyte fragility.']
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['Clinical and animal studies suggest that brain serotonergic systems may regulate aggressive behavior; however, the serotonin/violence hypothesis has not been assessed at the epidemiological level. For study of an epidemiological sample we examined blood serotonin, because certain physiological and behavioral findings suggested that it might serve as an analog marker for serotonergic function.', "Whole blood serotonin was measured in a representative birth cohort of 781 21-year-old women (47%) and men (53%). Violence was measured using cumulative court conviction records and participants' self-reports. Potential intervening factors addressed were: gender, age, diurnal variation, diet, psychiatric medications, illicit drug history, season of phlebotomy, plasma tryptophan, platelet count, body mass, suicide attempts, psychiatric diagnoses, alcohol, tobacco, socioeconomic status, IQ, and overall criminal offending.", "Whole blood serotonin related to violence among men but not women. Violent men's mean blood serotonin level was 0.48 SD above the male population norm and 0.56 SD above the mean of nonviolent men. The finding was specific to violence, as opposed to general crime, and it was robust across two different methods of measuring violence. Together, the intervening variables accounted for 25% of the relation between blood serotonin and violence."]
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['Previous in vitro studies have demonstrated that polyvinylpyrrolidone coated silver nanoparticles (PVP-coated AgNPs) have antiviral activity against HIV-1 at non-cytotoxic concentrations. These particles also demonstrate broad spectrum virucidal activity by preventing the interaction of HIV-1 gp120 and cellular CD4, thereby inhibiting fusion or entry of the virus into the host cell. In this study, we evaluated the antiviral activity of PVP-coated AgNPs as a potential topical vaginal microbicide to prevent transmission of HIV-1 infection using human cervical culture, an in vitro model that simulates in vivo conditions.', 'When formulated into a non-spermicidal gel (Replens) at a concentration of 0.15 mg/mL, PVP-coated AgNPs prevented the transmission of cell-associated HIV-1 and cell-free HIV-1 isolates. Importantly, PVP-coated AgNPs were not toxic to the explant, even when the cervical tissues were exposed continuously to 0.15 mg/mL of PVP-coated AgNPs for 48 h. Only 1 min of PVP-coated AgNPs pretreatment to the explant was required to prevent transmission of HIV-1. Pre-treatment of the cervical explant with 0.15 mg/mL PVP-coated AgNPs for 20 min followed by extensive washing prevented the transmission of HIV-1 in this model for 48 h.']
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['Toll-like receptors (TLRs) recognize pathogens and mediate signaling pathways important for host defense. Recent studies implicate TLR polymorphisms in atherosclerosis risk in humans. Adipocyte fatty acid-binding protein (aP2) is present in macrophages and has an important role in atherosclerotic plaque development. We investigated aP2 expression in RAW 264.7 cells treated with lipopolysaccharide (LPS) and other TLR agonists and assessed lipid accumulation in these activated murine macrophages.', 'Stimulation with LPS, a TLR4 ligand, resulted in a 56-fold increase in aP2 mRNA expression, and zymosan, a TLR2 ligand, induced an approximately 1500-fold increase. Polyinosine: polycytidylic acid (poly I:C), a TLR3 ligand, led to a 9-fold increase. Levels of aP2 protein were significantly increased in LPS or zymosan-treated macrophages compared with control or poly I:C-treated cells. In addition, the cholesteryl ester content of LPS or zymosan-treated macrophages was approximately 5-fold greater in the presence of low-density lipoprotein, and triglyceride content was approximately 2-fold greater in the absence of exogenous lipid than control or poly I:C-treated cells.']
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["A depletion of hyaluronic acid (HA) in patients' eyes may be associated with primary open-angle glaucoma (POAG), but the exact mechanism remains unclear. We investigated the effect of HA on the expression of matrix metalloproteinases (MMP-2 and MMP-9) in cultured trabecular meshwork cells.", 'Trabecular meshwork cells were cultured from trabecular tissues obtained from the POAG patients aged 23 to 45. The mRNA expression of MMP-2 and MMP-9 was determined by reverse transcription-polymerase chain reaction, and the protein expression of MMP-2 and MMP-9 by gelatin zymography analysis and qualified by the gel electrophoresis image analysis in different HA concentrations.', 'The expression of MMP-2 and MMP-9 by the two methods significantly increased with HA concentration in a dose-response manner. Mean values of the MMP-2 expression by the gelatin zymography analysis were 176, 264, 353, and 448 mg/ml, and mean values of the MMP-9 expression were 547, 659, 895, and 1,147 mg/ml, for HA concentration level of 0, 1, 3, and 6 mg/ml, respectively.']
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['Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.', 'A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).', "Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs."]
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