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['The aim of this study was to measure serum concentrations of total nitrites, as an index of nitric oxide synthesis, in the maternal and fetal circulations of normal pregnancies and in pregnancies complicated by preeclampsia.', 'We studied 32 women with preeclampsia and 36 with uncomplicated pregnancies. Maternal venous blood samples were collected from all of the patients, and umbilical venous blood was collected from 13 of the preeclamptic group and 17 of the control group. Serum nitric oxide concentrations were determined with the Greiss reaction by measuring combined oxidation products of nitric oxide, serum nitrite and nitrate after reduction with nitrate reductase.', 'There were no significant differences in maternal serum nitrite concentrations between the groups (control group 29.8 +/- 1.07 mumol/L, preeclamptic group 29.5 +/- 1.06 mumol/L). Significantly higher serum nitrite concentrations were found in umbilical venous serum in the preeclamptic group compared with the control group (34.59 +/- 1.12 mumol/L vs 23.90 +/- 1.05 mumol/L, p < 0.01).']
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['To compare coronary flow reserve in endurance athletes and healthy sedentary controls, using adenosine transthoracic echocardiography.', '29 male endurance athletes (mean (SD) age 27.3 (6.6) years, body mass index (BMI) 22.1 (1.9) kg/m(2)) and 23 male controls (age 27.2 (6.1) years, BMI 23.9 (2.6) kg/m(2)) with no coronary risk factors underwent transthoracic echocardiographic assessment of distal left anterior descending coronary artery (LAD) diameter and flow, both at rest and during intravenous adenosine infusion (140 microg/kg/min).', 'Distal LAD diameter and flow were adequately assessed in 19 controls (83%) and 26 athletes (90%). Distal LAD diameter in athletes (2.04 (0.25) mm) was not significantly greater than in sedentary controls (1.97 (0.27) mm). Per cent increase in LAD diameter following 400 microg sublingual nitrate was greater in the athletes than in the controls, at 14.1 (7. 2)% v 8.8 (5.7)% (p < 0.01). Left ventricular mass index in athletes exceeded that of controls, at 130 (19) v 98 (14) g/m(2) (p < 0.01). Resting flow among the athletes (10.6 (3.1) ml/min; 4.4 (1.2) ml/min/100 g left ventricular mass) was less than in the controls (14.3 (3.6) ml/min; 8.2 (2.2) ml/min/100 g left ventricular mass) (both p < 0.01). Hyperaemic flow among the athletes (61.9 (17.8) ml/min) exceeded that of the controls (51.1 (14.6) ml/min; p = 0.02), but not when corrected for left ventricular mass (25.9 (5.6) v 28.5 (7.4) ml/min/100 g left ventricular mass; NS). Coronary flow reserve was therefore substantially greater in the athletes than in the controls, at 5.9 (1.0) v 3.7 (0.7) (p < 0.01).']
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['Aspirin (acetylsalicylic acid) or ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] was administered to mice undergoing treatment of tuberculosis infection with pyrazinamide to determine if these non-steroidal anti-inflammatory drugs (NSAIDs) enhance pyrazinamide activity in vivo.', 'BALB/c mice were infected with Mycobacterium tuberculosis H37Rv through aerosol exposure. Mice were treated orally with aspirin, ibuprofen or pyrazinamide, alone and in combination. The impact of daily administration of these drugs for 1 month was determined by enumerating viable bacteria in the lung and spleen.', 'Aspirin or ibuprofen alone at 20 mg/kg per day had little effect on tuberculosis infection after 1 month of treatment, while pyrazinamide at 150 mg/kg per day led to a reduction of about 1.5 log(10) cfu in the lung and 2 log(10) cfu in the spleen compared with the control. Simultaneous administration of either aspirin or ibuprofen with pyrazinamide resulted in a further decrease of about 0.4 log(10) cfu in the lung and more than 1 log(10) cfu in the spleen compared with mice receiving pyrazinamide alone. All spleens in the pyrazinamide-only treatment group were positive for infection. Of mice treated with both aspirin and pyrazinamide, two of five spleens were negative for colony formation, with a lower limit of detection of 0.90 log(10) cfu per organ. Three of five mice given ibuprofen and pyrazinamide had culture-negative spleens.']
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['Cardiovascular disease is a major problem in patients with chronic renal failure leading to increased mortality. Several infectious agents have been implicated to be associated with atherosclerosis. We were interested to evaluate whether there is a correlation between a past infection with Chlamydia pneumoniae (Cpn), Helicobacter pylori (Hp) or cytomegalovirus (CMV) and the manifestation of a symptomatic atherosclerotic disease in patients with endstage renal failure.', 'Patients (n=267) on hemodialysis were investigated. In 101 patients with an apparent atherosclerotic disease (case group) increased IgA levels against Cpn were found (p < or = 0.0001 vs. controls; n=33). Nearly 45% of the case group had a history of myocardial infarction (MI) (p < or = 0.0001). Prior stroke was found in about 30% of patients in the case group (p < or = 0.002). Elevated CRP levels were identified as an independent risk factor for atherosclerosis in all groups. IgA seropositivity against Cpn correlated with elevated CRP values for all atherosclerotic patients (p < or = 0.001), especially in the group of patients with MI (p < or = 0.019) and peripheral vascular disease (p < or = 0.005). There was no correlation between CMV (IgG, IgM) or Hp (IgA, IgG) seropositivity and atherosclerotic disease.']
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['Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain. Excessive glutamatergic transmission and loss of cholinergic neurons are the major indicators of HAND. Nicotine acts as a cholinergic channel modulator, and its cognitive-enhancing effect in neurodegenerative and cognitive disorders has been documented. However, it is unclear whether nicotine has any positive effect on memory and synaptic plasticity formation in HAND.', 'We investigated the effects of nicotine on synaptic plasticity and hippocampus-prefrontal cortex (PFC)-amygdala-dependent memory formation in the HIV-1 transgenic (Tg) and F344 control rats.', 'Chronic nicotine treatment (0.4\xa0mg/kg nicotine, base, subcutaneously) significantly attenuated the cognitive deficits in the HIV-1Tg rats in both the spatial and contextual fear memories but impaired the contextual learning memory in the F344 rats. To determine the role of nicotine in the synaptic dysfunction caused by HIV-1 proteins, we analyzed the expression of key representative genes related to synaptic plasticity in the hippocampus, PFC, and amygdala of the HIV-1Tg and F344 rats using a custom-designed qRT-PCR array. The HIV-1 proteins significantly altered the glutamate receptor-mediated intracellular calcium cascade and its downstream signaling cascade in a brain region-specific manner. Further, chronic nicotine treatment reversed the effect of HIV-1 proteins on the expression of genes involved in synaptic plasticity in the three brain regions. The effects of nicotine differed significantly in the HIV-1Tg and F344 rats.']
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['Increasing evidence suggests that posttraumatic stress disorder (PTSD) is associated with small hippocampal size. The authors compared trauma-exposed subjects with PTSD and trauma-exposed subjects without PTSD to clarify whether small hippocampal size is related to PTSD or to mere trauma exposure.', 'Three-dimensional structural magnetic resonance imaging was used to assess hippocampal volumes in 30 men who had recently been exposed to a severe burn trauma and 15 matched healthy comparison subjects.', 'Relative to the comparison subjects, the trauma-exposed subjects with PTSD (N=15) as well as the trauma-exposed subjects without PTSD (N=15) had significantly smaller volumes of the right hippocampus (subjects with PTSD: -12%; subjects without PTSD: -13%). Larger total areas of burned body surface were significantly related to smaller left hippocampal volumes. Use of analgesic/sedative treatment with the N-methyl-d-aspartic acid (NMDA) antagonist ketamine was significantly related to larger right hippocampal volumes and to stronger PTSD symptoms.']
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['To test whether lipoxin A4 (LXA4) deficiency results in preeclampsia.', 'Prospective experimental study.', 'Patient and animal research facilities.', 'Sprague-Dawley rats.', 'We measured LXA4 and its biosynthetic enzymes, blocked the LXA4 signaling pathway, treated experimental rats with preeclampsia with LXA4, and detected inflammatory factors, FPR2/ALX, and 11β-HSD2 to systematically test whether lack of LXA4 results in preeclampsia.', 'We measured serum levels of LXA4 and inflammatory factors using enzyme-linked immunosorbent assay; detected LXA4 biosynthetic enzymes, inflammatory factors, FPR2/ALX, and 11β-HSD2 mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; and localized protein expression using immunohistochemistry.', 'FPR2/ALX and LXA4 and its biosynthetic enzymes were found to be decreased in women with preeclampsia. Replenishing LXA4 improved the symptoms of lipopolysaccharide-induced rats with preeclampsia, while blocking LXA4 signaling resulted in preeclampsia. LXA4 significantly reduced interleukin-6 (IL-6), tumor necrosis factor-α, and IFN-γ but increased IL-10, LXA4 up-regulated 11β-HSD2.']
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['Upper respiratory infections (URI) presage perioperative respiratory complications, but thresholds to cancel surgery vary widely. We hypothesized that autonomically-mediated complications seen during emergence from anesthesia would be predicted by capnometry and reduced with preoperative bronchodilator administration.', 'Afebrile outpatient tertiary-care children (age two months to 18 yr, n = 109) without lung disease or findings, having non-cavitary, non-airway surgery for under three hours, were randomized to bronchodilator premedication vs placebo and had preoperative capnometry. After halothane via mask, laryngeal mask airway, or endotracheal tube, and regional anesthesia as appropriate, patients recovered breathing room air while cough, wheeze, stridor, laryngospasm, and cumulative desaturations were recorded for 15 min.', 'In this specific population, there was no association between adverse events and either URI within six weeks (n = 76) or URI within seven days (n = 21). Neither albuterol nor ipratropium premedication decreased adverse events. Endotracheal intubation was associated with increased emergence desaturations and placebo nebulized saline increased emergence coughing. Neither anesthesiologists nor preoperative capnometry predicted adverse events.']
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['Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level.', 'Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004-2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1- ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2- modern/TbD1-/PGG1 group (Beijing, CAS), group 3- evolutionary recent/TbD1-/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%.']
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['Ezetimibe is a hypolipidemic agent acting via inhibition of cholesterol absorption from the small intestine. The effectiveness and safety of long-term administration of ezetimibe was evaluated in renal allograft recipients with persistent hyperlipidemia.', '67 renal allograft recipients with post-transplantation hyperlipidemia resistant to statins were included in the study; 11 were treated with ezetimibe (10 mg/day) alone and 56 with ezetimibe and statin. The effectiveness of ezetimibe was assessed by determination of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides (TR). Its safety was determined by liver enzymes (ALT, AST), LDH, CPK, serum creatinine and blood levels of immunosuppressive drugs (cyclosporine, tacrolimus, everolimus, sirolimus) over the follow-up period of 18±6 months.', 'A significant reduction of TC and LDL-C blood levels by 25% and 34% respectively, was observed during the first month of treatment with ezetimibe (p<0.001). This reduction was maintained for the whole period of ezetimibe administration. Renal function remained stable over the follow-up period, while no changes of the blood levels of immunosuppressive drugs were observed. Liver enzymes, LDH and CPK remained normal in all patients except for one diabetic patient who developed rhabdomyolysis. Apart from gastrointestinal symptoms in 2 patients, no other side effects were observed.']
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['The zinc finger transcription factor early growth response gene 1 (EGR1) is underexpressed in non-small-cell lung cancer (NSCLC) compared with normal lung. EGR1 expression has been linked to tumor suppression as a result of cell cycle arrest and apoptosis through regulation of tumor suppressor pathways including PTEN. For these reasons, we hypothesized that reduced levels of EGR1 would correlate with inferior outcome in patients with NSCLC.', 'Patients who underwent surgical resection for NSCLC had RNA extracted from tumor tissue and EGR1 gene expression was quantified by real-time quantitative polymerase chain reaction. The levels of EGR1 expression were examined in relationship to patient characteristics, histology, tumor stage, PTEN expression, and overall and disease-free survival.', 'EGR1 expression strongly correlated with PTEN expression (P < .0001). No correlation of EGR1 with histology or stage was detected. Patients with high levels of EGR1 had better overall and disease-free survival compared with patients with low levels of EGR1 (P = .040 and P = .096, respectively). In a stratified log-rank test, low EGR1 expression was predictive of poor survival independent of tumor stage.']
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['A sound predictive test is lacking for the identification of cirrhotic patients at high risk of developing hepatocellular carcinoma. The present study evaluates the measurement of hepatocyte expression of silver stained nucleolar organiser region (AgNOR) proteins as a risk factor for the development of hepatocellular carcinoma in cirrhosis.', 'Liver biopsies from 176 cirrhotic patients included in a follow up surveillance programme for hepatocellular carcinoma development were evaluated prospectively for hepatocyte AgNOR protein quantity. The follow up programme consisted of clinical and biochemical assessment every three months, and ultrasound scanning and serum alpha-fetoprotein (alpha FP) assessment every six months. Histological sections from the needle biopsies performed at enrollment were stained selectively for AgNOR proteins and the percentage of hepatocytes with an AgNOR protein area > or = 7 micron 2, indicative of a proliferative state (AgNOR proliferation index (AgNOR-PI)), was measured.', 'During the mean (SD) follow up time of 65.5 (36.29) months (range, 12-143; median, 67), hepatocellular carcinoma was diagnosed in 48 of 176 patients (27.3%). The AgNOR-PI of the whole series ranged from 0% to 5% (median, 0.9%), and was significantly higher in patients with liver cell dysplasia and hepatitis B surface antigen (HBsAg) positivity (p < 0.0001 and p = 0.0002, respectively). The 176 patients were divided into two groups according to their AgNOR-PI scores; a cut off value of 2.5% defined by the receiver operating characteristic curve and the Youden index was used. Forty two patients were included in the high AgNOR-PI (< 2.5%) group, and 134 patients the low AgNOR-PI (< 2.5%) group. In the high AgNOR-PI group, 25 of 42 patients developed hepatocellular carcinoma, in contrast to only 23 of 134 patients (17.2%) in the group with a low AgNOR-PI (p < 0.0001). Hepatocellular carcinoma development was also significantly more frequent in patients with liver cell dysplasia and HBsAg positivity. Multivariate analysis using AgNOR-PI, liver cell dysplasia, HBsAg positivity, and hepatitis C virus (HCV) infection as covariates demonstrated that the AgNOR-PI parameter was the only significant predictor of hepatocellular carcinoma development.']
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['Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model.', 'Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo.', 'CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model.']
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['Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85\xa0years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species.', 'We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708\xa0Mb and 734\xa0Mb and correspond to 98\xa0% and 102\xa0% of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52\xa0bp to 1 per 69\xa0bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus.']
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['Patient nonadherence to cardiac medications following acute coronary syndrome (ACS) is associated with increased risk of recurrent events. However, the prevalence of cognitive dysfunction and poor health literacy among ACS patients and their association with medication nonadherence are poorly understood.', 'We assessed rates of cognitive dysfunction and poor health literacy among participants of a clinical trial that tested the effectiveness of an intervention to improve medication adherence in patients hospitalized with ACS. Of 254 patients, 249 completed the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) survey, an assessment of risk for poor literacy, and the St Louis University Mental Status (SLUMS) exam, a tool assessing for neurocognitive deficits, during ACS hospitalization. We assessed if SLUMS or REALM-R scores were associated with medication adherence.', 'Based on SLUMS score, 14% of patients were categorized as having dementia, and 52% with mild neurocognitive disorder (MNCD). Based on REALM-R score of ≤6, 34% of patients were categorized as at risk for poor health literacy. There was no association between poor health literacy and medication nonadherence. Of those with MNCD, 35.5% were nonadherent, compared to 17.5% with normal cognitive function and 6.7% with dementia. In multivariable analysis, cognitive dysfunction was associated with medication nonadherence (P=0.007), mainly due to an association between MNCD and nonadherence (odds ratio =12.2, 95% confidence interval =1.9 to 243; P=0.007). Cognitive status was not associated with adherence in patients randomized to the intervention.']
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['For severe burn victims suffering from total loss of upper and lower eyelids, skin graft or skin flap is normally used to cover the lesion and to protect the cornea, preventing corneal ulcer and simultaneously preparing for corneal transplantation. However, a new problem arises after the formation of the new palpebral fissure, that is, the reconstructed eyelids cannot open and close like the normal eyelids and the eyeball movement is limited, which exposes the cornea to dry air resulting in ulceration. In this article, we present a simple technique to partially solve this problem.', "Five burn victims who lost their eyelids received treatment: stumps of upper and lower eyelids bulbar conjunctiva were dissected and pulled together as the lining of the conjunctival sac. Intermediate split-thickness skin was then immediately grafted as the new eyelids' skin. After 3 months, a 2-cm transverse incision was made 5mm below the normal palpebral fissure to open the conjunctival sac and new 'eyelids' were formed.", 'The patients were followed for 2-9 years. No lagophthalmos and xerophthalmia were found. When the patients raised their heads in the supine position, they could see outside. When they bowed their heads, the cornea was protected. Their remaining vision was rescued and an average 0.4 vision recovered. Most of the patients went back to work.']
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['The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem.', 'Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort.', 'A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45).']
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['Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of beta-cell autoantibodies (A+ or A-) and beta-cell functional reserve (beta+ or beta-). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenotypes.', 'A total of 185 adults presenting with diabetic ketoacidosis were followed longitudinally for a mean of 5.5 years, with measurements of autoantibodies, beta-cell functional reserve, insulin sensitivity, and insulin requirement. Frequencies of susceptibility and resistance alleles at HLA DQA1, DQB1, and DRB1 loci were correlated with clinical and phenotypic features of KPD subgroups and compared with those of ethnic-specific population control subjects.', 'Susceptibility alleles were more frequent (P < 0.0001) in the two A+ than the two A- KPD subgroups; in the latter, the frequency was no greater than in population control subjects (except for DQB1*0302). Susceptibility alleles differentiated the two clinically similar beta- subgroups (more frequent in A+beta- than A-beta- KPD; P < 0.01). Resistance alleles were more frequent in the two beta+ than the two beta- KPD subgroups (P < 0.01). The frequencies of certain susceptibility (e.g., DQB1*02) and resistance (DQB1*0602) alleles were higher in African-American A-beta+ KPD patients than in African-American control subjects. DQB1*0302 was more frequent in all KPD subgroups compared with control subjects.']
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['Homocysteine is associated with an increased risk of atherosclerosis. The administration of fibrates has been reported to significantly increase plasma homocysteine levels, a potentially adverse effect of fibrates. We investigated the hypothesis that concomitant treatment with fenofibrate and folic acid leads to a smaller increase in plasma total homocysteine levels than treatment with fenofibrate alone.', 'A randomized, open-label study compared the effect of micronized fenofibrate (200 mg daily) alone versus fenofibrate plus folic acid (10 mg every other day) on plasma homocysteine levels. Twenty-two patients with mixed hyperlipidemia participated. The 9-wk treatment period was preceded by a 4-wk wash-out period without hypolipidemic drugs.', 'In patients treated with fenofibrate only, plasma homocysteine levels increased by 6.85 +/- 5.23 micromol/L (from 12.27 +/- 3.15 to 19.13 +/- 7.20 micromol/L); in patients treated with fenofibrate and folic acid, plasma homocysteine levels increased by 2.01 +/- 2.88 micromol/L (from 10.14 +/- 2.32 to 12.15 +/- 3.08 micromol/L). The difference in the homocysteine increase between the two groups was statistically significant at P = 0.014.']
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['Fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). We investigated several factors associated with the persistence of transforming growth factor beta (TGF-β)-induced fibrosis and whether these factors also play a role in OA-related fibrosis.', 'Mice were injected intra-articularly (i.a.) with an adenovirus encoding either TGF-β or connective tissue growth factor (CTGF). In addition, we induced OA by i.a. injection of bacterial collagenase into the right knee joint of C57BL/6 mice. mRNA was isolated from the synovium for Q-PCR analysis of the gene expression of various extracellular matrix (ECM) components, ECM degraders, growth factors and collagen cross-linking-related enzymes. Sections of murine knee joints injected with Ad-TGF-β or Ad-CTGF or from experimental OA were stained for lysyl hydroxylase 2 (LH2). The number of pyridinoline cross-links per triple helix collagen in synovium biopsies was determined with high-performance liquid chromatography (HPLC).', 'Expression of collagen alpha-1(I) chain precursor (Col1a1), tissue inhibitor of metalloproteinases 1 (TIMP1) and especially procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2b (Plod2b) were highly upregulated by TGF-β but not by CTGF. Elevated expression of Plod2b mRNA was associated with high lysyl hydroxylase 2 (LH2) protein staining after TGF-β overexpression and in experimental OA. Furthermore, in experimental OA the number of hydroxypyridinoline cross-links was significant increased compared to control knee joints.']
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['Observational and experimental studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however, clinical trials and other observational studies, including the Adult Changes in Thought (ACT) study, show no protection or promotion of AD. The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure.', 'We examined the association of mid- to late-life NSAID use with neuropathologic findings on 257 autopsies from ACT, a population-based study of brain aging and incident dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were determined from ≥10 years of computerized pharmacy dispensing data. Analyses were adjusted for selection bias to broaden generalizability of results to 3,026 eligible participants in the ACT cohort. Seven pathologic indices were evaluated: intermediate or frequent score for neuritic plaques, Braak stages V or VI for neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and moderate or severe atherosclerosis.', 'Of the neuropathologic indices evaluated, only neuritic plaque score was significantly increased in participants with greater use of nonselective NSAIDs (p = 0.065), specifically in those with high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67).']
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['Nerve root traction injuries induce spinal cord inflammation and lead to neuronal death within days. In the present study, we examined the inflammatory response one week after multiple cervical root transections.', 'In the transection group, the left cervical roots (C6-8) of rats were cut at the spinal cord junction. In the repair group, transected roots were repaired with nerve grafts and the subsequent application of aFGF and fibrin glue. A sham group had nerve roots exposed without transection. Mechanical allodynia and spinal glial responses were evaluated.', 'Allodynia did not differ between the treatment groups on day 2. Rats with transected spinal nerve roots had significantly more allodynia by 7 days, which was associated with IL-1β expression in dorsal and ventral horn astrocytes, and microglia activation. Repair of nerve roots with autologous intercostal nerve grafts and FGF in fibrin glue attenuated the allodynia, reduced IL-1β expression in astroctyes and reduced microglia activation, along with a significant increase in arginase I expression.']
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['The purpose of this study was to investigate tibial changes in volumetric bone mineral density and geometry that take place in athletes from pre- to post-season.', 'Female college athletes (n\xa0=\xa036) and ten controls recruited from the student population were included in the study. Participants had their left tibia scanned by pQCT at 4, 20, and 66\xa0% of the overall length from the distal end before and after their competitive seasons. Subjects were divided into four groups: non-athlete (controls, n\xa0=\xa010), moderate-impact (cross-country runners, n\xa0=\xa013), high-impact (volleyball and basketball, n\xa0=\xa011), and odd-impact (soccer, n\xa0=\xa012).', 'Anterior-posterior and medial-lateral diameter increased at the 4\xa0% site in control subjects. In the moderate-impact group, medial-lateral moment of inertia (MOI) increased by 1.2\xa0±\xa01.8 (mean\xa0±\xa0SD) percent at the 20\xa0% site. In high-impact group, anterior-posterior MOI increased by 1.6\xa0±\xa02.0 percent at the 66\xa0% site. In odd-impact group, cortical area (1.4\xa0±\xa02.3\xa0%) and cortical thickness (1.8\xa0±\xa02.8\xa0%) increased at the 20\xa0% site increased, as did the polar MOI (1.8\xa0±\xa02.2\xa0%) at the 66\xa0% site.']
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['Myotonia and periodic paralysis caused by sodium channel mutations show variable responses to the anti-myotonic drug mexiletine.', 'To investigate whether variability among sodium channel mutants results from differences in drug binding affinity or in channel gating.', 'Whole-cell sodium currents (I(Na)) were recorded in tsA201 cells expressing human wild-type (WT) and mutant skeletal muscle sodium channels (A1156T, hyperkalemic periodic paralysis; R1448C, paramyotonia congenita; G1306E, potassium-aggravated myotonia).', 'At a holding potential (hp) of -120 mV, mexiletine produced a tonic (TB, 0.33 Hz) and a use-dependent (UDB, 10 Hz) block of peak I(Na) with a potency following the order rank R1448C > WT approximately equal A1156T > G1306E. Yet, when assayed from an hp of -180 mV, TB and UDB by mexiletine were similar for the four channels. The different midpoints of channel availability curves found for the four channels track the half-maximum inhibitory value (IC50) measured at -120 mV. Thus differences in the partitioning of channels between the closed and fast-inactivated states underlie the different IC50 measured at a given potential. The mexiletine-derivative, Me7 (alpha-[(2-methylphenoxy)methyl]-benzenemethanamine), behaved similarly but was approximately 5 times more potent than mexiletine. Interestingly, the higher drug concentrations ameliorated the abnormally slower decay rate of myotonic I(Na).']
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['Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis. As comorbidity and frailty increase with age; ethical dilemmas may arise when OHCA occur in the very old.', 'We aimed to investigate mortality, neurological outcome and post resuscitation care in octogenarians (≥80) to assess whether resuscitation and post resuscitation care should be avoided.', 'During 2007-2011 consecutive OHCA-patients were attended by the physician-based Emergency Medical Services-system in Copenhagen. Pre-hospital data based on Utstein-criteria, and data on post resuscitation care were collected. Primary outcome was successful resuscitation; secondary endpoints were 30-day mortality and neurological outcome (Cerebral Performance Category (CPC)).', '2509 OHCA-patients with attempted resuscitation were recorded, 22% (n=558) were octogenarians/nonagenarians. 166 (30% of all octogenarians with resuscitation attempted) octogenarians were successfully resuscitated compared to 830 (43% with resuscitation attempted) patients <80 years. 30-day mortality in octogenarians was significantly higher after adjustment for prognostic factors (HR=1.61 CI: 1.22-2.13, p<0.001). Octogenarians received fewer coronary angiographies (CAG) (14 vs. 37%, p<0.001), and had lower odds of receiving CAG by multivariate logistic regression (OR: 0.19, CI: 0.08-0.44, p<0.001). A favorable neurological outcome (CPC 1/2) in survivors to discharge was found in 70% (n=26) of octogenarians compared to 86% (n=317, p=0.03) in the younger patients.']
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['Special AT-rich binding protein-1 (SATB1) reprograms chromatin organization and transcription profiles to promote tumour growth and metastasis.', 'This study aimed to confirm the effects of SATB1 on the growth and metastasis of liver cancer and its specific regulation mechanism.', 'SATB1 expression was evaluated in human hepatoma tissue, adjacent noncancerous tissue and seven kinds of liver cancer cell lines. Cell cycle, cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) was investigated after enhanced or silenced expression of SATB1. The regulatory action of SATB1 on the expression of genes that are known to regulate cell cycle progression, apoptosis and EMT and the specific apoptotic pathway on which it acts were further analysed. Nude mice that received subcutaneous implantation were used to study the effects of SATB1 on tumour growth in vivo.', 'Our data show that the high expression of SATB1 was observed in the human hepatocellular carcinoma tissue (26/45) and liver cancer cell lines with high metastatic potential. SATB1 upregulated CDK4 and downregulated p16 (INK) (4A) to promote cell cycle progression and cell proliferation and prevented apoptosis by inhibiting the FADD-caspase-8-caspase-3 death receptor-mediated apoptosis pathway. SATB1 also induced EMT concomitant with increased expression of Snail1, Slug, Twist and vimentin and decreased expression of E-cadherin, tight junction protein ZO-1 and desmoplakin. SATB1 promoted the growth of tumour in vivo.']
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['The role of the pulmonary vasculature in the pathogenesis of ventilator-induced lung injury is not well established. In this study, the authors investigated the effect of vascular remodeling due to chronic pulmonary hypertension on susceptibility to ventilator-induced lung injury. The authors hypothesized that the enhanced vascular tensile strength associated with pulmonary vascular remodeling would protect against ventilator-induced lung injury.', 'Chronic pulmonary arterial hypertension was induced in rats by exposure to hypoxia for 28 days and was confirmed by demonstration of right ventricular hypertrophy. Normotensive and hypertensive groups of rats (as well as a group in which pulmonary hypertension was acutely reversed with a Rho-kinase inhibitor, Y-27632) were exposed to injurious ventilation (respiratory rate 30 min, 30/0 cm H2O) for 90 min. Lung injury was assessed by change in lung mechanics, oxygenation, edema development, and cytokine levels. Electron microscopy was used to examine vascular structure in additional animals.', 'Injurious ventilation caused significant lung injury (lung compliance, oxygenation, pulmonary edema) in the normotensive controls, but not in the presence of pulmonary hypertension; acute reversal of pulmonary hypertension did not alter the lessened susceptibility to ventilator-induced lung injury. Electron microscopy demonstrated capillary endothelial and epithelial breaks in injuriously ventilated normotensive controls that were not seen with pulmonary hypertension, whether or not the pulmonary hypertension was acutely reversed.']
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['Atrial fibrillation (AF) is characterized by an irregularly irregular ("random") heart beat. However, controversy exists whether the ventricular rhythm in AF is truly random. We investigated randomness by constructing three-dimensional RR interval plots (3D plots), allowing identification of "clustering" of RR intervals. It was hypothesized that electrical cardioversion (ECV) would be more effective in AF patients with clustering, because clustering might reflect a higher degree of organization of atrial fibrillatory activity.', 'The study group consisted of 66 patients (44 men and 22 women; mean age 68 +/- 11 years), who were referred for ECV because of persistent AF. Twenty-four-hour Holter recordings were used to construct 3D plots by plotting each RR interval (x axis) against the previous RR interval (y axis) and the number of occurrences of each of these x,y combinations (z axis). A clustering index was calculated as the percentage of beats within the peaks in the 3D plot. Based on the 3D plots, clustering of RR intervals was present in 31 (47%) of the 66 patients. ECV was effective in restoring sinus rhythm in 29 (94%) of these 31 patients, whereas sinus rhythm was restored in only 25 (71%) of the remaining 35 patients without clustering (P = 0.020). The clustering index ranged from <2% in the 12 patients with failed ECV to >8% in the 32 patients with sinus rhythm at the end of the study (4 weeks after the ECV); the clustering index in the 22 patients with a relapse of AF after effective ECV was intermediate (P = 0.034 and P = 0.042, respectively).']
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['The aim of this study was to determine the association of early treatment intensity with hospital mortality of intensive care unit (ICU) patients.', 'We performed an observational study based on a national ICU registry. We included adult patients treated in Finnish ICUs between 2003 and 2013 with the length of ICU stay of more than 3 days. We measured treatment intensity with the Therapeutic Intervention Scoring System (TISS-76). We assessed mean and daily TISS scores. To define the change in treatment intensity during the first days in the ICU, we calculated the difference between the TISS score on day 3 and the score on day 1 (ΔTISS). We used multivariate logistic regression to adjust for baseline differences and continuous net reclassification improvement (NRI) to determine the impact of adding TISS data to the baseline prediction model on its prognostic performance.', 'We identified 42,493 patients eligible for the study. For 71% of the patients, ΔTISS was ≤ 0 and crude hospital mortality was 18%. ΔTISS > 0 was observed for 29% of the patients, with a hospital mortality of 23%. When compared to the group ΔTISS ≤ 0, the category ΔTISS > 0 was independently associated with substantially increased mortality. Adding TISS data to the prediction model resulted in the improvement of prognostic performance particularly in the patients with the lowest initial baseline risk.']
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['Chaperones play an important role in inducing anti-cancer immunity. To explore the probability of using chaperone-peptide-rich complexes extracted from colo-carcinoma cells as anti-cancer vaccine, we extracted and prepared chaperone-peptide-rich complexes from CT26 cells, which were subsequently investigated on anti-cancer efficacy.', 'The crude extracts of the CT26 cells treated with heat and Trichosanthin were precipitated with salt and dialyzed to remove proteins below 50kDa and above 300kDa in molecular weight; the proteins with the molecular weights in 70kDa, 90kDa, 95kDa, 110kDa and 170kDa were collected through gel filtration and SDS-PAGE. After confirmation, the purified proteins were used to determine their effects on lymphocyte proliferation, the activities of NK and CTL, tumor suppression and the tumor-bearing mouse survival.', 'The majority of the chaperone-peptides of anti-cancer immunity in CT26 cells, including HSP70-antigen peptide, HSP90-antigen peptide, gp96-antigen peptide, HSP-110 antigen peptide, HSP170-antigen peptide, was satisfactorily extracted that the multi-chaperone-peptide-rich mixtures were obtained. All the mixtures prepared could elicit lymphocyte proliferation, enhance the activities of CTL and NK, reinforce the tumor suppression and prolong the mouse survival.']
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['For older adults, falls threaten their health, independence, and quality of life. Knowing the circumstances surrounding falls is essential for understanding how behavioral and environmental factors interact in fall events. It is also important for developing and implementing interventions that are effective and acceptable to older adults. This study investigated the circumstances and injury outcomes of falls among community-dwelling older adults at high risk for falls.', 'In this secondary analysis, we examined the circumstances and outcomes of falls experienced by 328 participants in the Dane County (Wisconsin) Safety Assessment for Elders (SAFE) Research Study. SAFE was a randomized controlled trial of a community-based multifactorial falls intervention for older adults at high risk for falls, conducted from October 2002 to December 2007. Participants were community-dwelling adults aged ≥65\xa0years who reported at least one fall during the year after study enrollment. Falls were collected prospectively using monthly calendars. Everyone who reported a fall was contacted by telephone to determine the circumstances surrounding the event. Injury outcomes were defined as none, mild (injury reported but no treatment sought), moderate (treatment for any injury except head injury or fracture), and severe (treatment for head injury or fracture).', 'Data were available for 1,172 falls. A generalized linear mixed model analysis showed that being aged ≥85 (OR\u2009=\u20092.1, 95% confidence interval [CI]\u2009=\u20091.2-3.9), female (OR\u2009=\u20092.1, 95% CI\u2009=\u20091.3-3.4), falling backward and landing flat (OR\u2009=\u20095.6, 95% CI\u2009=\u20092.9-10.5), sideways (OR\u2009=\u20094.6, 95% CI\u2009=\u20092.6-8.0) and forward (OR\u2009=\u20093.3, 95% CI\u2009=\u20092.0-5.7) were significantly associated with the likelihood of injury. Of 783 falls inside the home, falls in the bathroom were more than twice as likely to result in an injury compared to falls in the living room (OR\u2009=\u20092.4, 95% CI\u2009=\u20091.2-4.9).']
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['It is increasingly recognized that asthma is a heterogeneous disease. Therefore, it is possible that analysis of gene expression in the airway will reveal clinically meaningful transcriptional endotypes of asthma (TEA clusters).', 'We measured whole transcriptome gene expression profiles in the sputum and whole blood of 100 individuals with asthma and 12 control subjects using the Affymetrix HuGene ST 1.0 gene arrays. Unsupervised clustering was conducted using pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG). This identified three TEA clusters that were correlated with clinical, physiologic, and inflammatory characteristics of the disease. TEA cluster 1 is a cluster of patients with asthma with a significantly higher rate of intubation (P\u2009=\u20090.05), a lower prebronchodilator FEV1 (P\u2009=\u20090.006), a higher bronchodilator response (P\u2009=\u20090.03), and higher exhaled nitric oxide levels (P\u2009=\u20090.04) than the other two TEA clusters. TEA cluster 2 has a higher rate of hospitalization for asthma (P\u2009=\u20090.04) and is heterogeneous. TEA cluster 3 is the largest cluster and has normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. TEA cluster 1 had the highest sputum Th2 gene signature (IL-4, -5, and -13) compared with the other clusters. A classifier was developed that predicts TEA cluster assignment using 53 predictive genes in the circulation. The classifier was applied to gene expression data of children from the Asthma Biorepository for Integrative Genomic Exploration (Asthma BRIDGE) consortium cohort and confirmed that TEA clusters 1 and 2 are associated with history of intubation (P\u2009=\u20095.58\u2009×\u200910(-06)) and hospitalization (P\u2009=\u20090.01), respectively.']
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['Periodic limb movements in sleep (PLMS) are common in the elderly. A previous large polysomnographic (PSG) study examining the relationship of PLMS to sleep architecture and arousals from sleep in women found that leg movements were common in elderly women, and PLMS which were associated with EEG arousals had a strong and consistent association with markers of disturbed sleep. Since sleep differs in men and women, we now investigate the association between PLMS and PSG indices of sleep quality in a large community-based sample of older men.', 'Observational study, cross-sectional analyses.', 'Six clinical sites participating in the Osteoporotic Fractures in Men (MrOS) Study.', '2,872 older community-dwelling men (mean age 76.4 years) who completed in-home PSG from 2003-2005.', 'N/A.', 'In-home PSG was performed which included bilateral measurement of leg movements. The total number of leg movements per hour of sleep (PLMI) and the number of leg movements causing EEG-documented arousals per hour of sleep (PLMA) were computed. A PLMI ≥ 5 (70.8%) and PLMA ≥ 5 (27.4%) were both prevalent. Linear regression models were used to examine the relationship between PLMS as predictors and sleep architecture, arousal index, and sleep efficiency as outcomes. The highest quintiles of PLMI (≥ 65.1) and PLMA (≥ 6.8) showed the largest association with indices of sleep architecture; PLMA showed a larger magnitude of effect. After multivariate adjustment, participants with a higher PLMA had a small but significantly higher arousal index, lower sleep efficiency, higher percentages of stages 1 and 2 sleep, and lower percentages of stage 3-4 and REM sleep (p < 0.01). An increased PLMI was similarly associated with a higher arousal index, higher percentage of stage 2 sleep, and lower percentage of stage 3-4 (p < 0.0001), but not with an increase in stage 1, REM sleep, or sleep efficiency. Neither PLMI nor PMLA was associated with subjective sleepiness measured by the Epworth Sleepiness Scale.']
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['To determine the number, type, precipitating factors and mortality associated with diabetic emergencies admitted to Groote Schuur Hospital.', 'Administered questionnaire survey.', 'Groote Schuur Hospital, Cape Town.', 'All patients admitted from September 1991 to January 1992 with elevated blood glucose concentrations who required intravenous insulin and fluids were evaluated by an administered questionnaire prior to discharge from hospital. Patients were divided into four groups according to presence of ketosis, standard bicarbonate level and serum osmolality: (i) mild diabetic keto-acidosis (DKA); (ii) severe DKA; (iii) hyperosmolar state; and (iv) hyperglycaemia.', 'There were 131 admissions in 122 patients. Sixty-five occurred in non-insulin-dependent diabetics, 45 in insulin-dependent diabetics and 12 in pancreatic diabetics. There were similar numbers of admissions in the four groups of hyperglycaemic emergencies. The mortality rate was 3% in the mild DKA and hyperglycaemic groups, significantly lower (P < 0.05) than in the hyperosmolar group (19%). The mortality rate was 11% in the severe DKA group (P > 0.05 v. other groups). Sixty-two per cent of participants had achieved Standard 4 to Standard 8 education. Only 39% were employed at the time of interview. Diabetic knowledge and general compliance were assessed as poor. Infections and poor compliance with hypoglycaemic therapy were the dominant precipitating factors.']
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['Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined.', 'BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae.', 'Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001).']
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['Matrix metalloproteinases play a role in regulating cardiac remodeling. We previously reported an association between tissue inhibitor of metalloproteinase 2 (TIMP-2) expression and mitral valve (MV) disease. However, the determinants and prognostic value of mitral TIMP2 after MV surgery are unknown.', 'This retrospective study of 164 patients after MV surgery in a tertiary medical center in Taiwan assessed mitral TIMP2 on a semiquantitative scale (0-2) by immunohistochemical staining. The primary endpoints were the composite of cardiovascular death and heart failure admission.', 'Mean age was 50.4±13.7 years. After a mean follow-up period of 101±59 months, primary endpoints had occurred in 25 (15.2%) subjects. Patients with and without primary endpoint events significantly differed in terms of age (56.6±14.4 vs. 49.2±13.4 years, respectively; p\u200a=\u200a0.013) and left ventricular end-systolic diameter (LVESD) (39.7±8.2 vs. 35.5±7.5 mm, p\u200a=\u200a0.010) at surgery. The TIMP2 had a significant dose-dependent association with development of a primary endpoint (p\u200a=\u200a0.002). Kaplan-Meier analysis showed that TIMP2 expression has a significant positive association with primary endpoint-free survival (log-rank test; p\u200a=\u200a0.004). Cox regression analysis showed that independent predictors of primary endpoints were TIMP2 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.12-0.65; p\u200a=\u200a0.003), age (HR 1.05; 95% CI 1.02-1.09; p\u200a=\u200a0.003) and LVESD (HR 1.05; 95% CI 1.01-1.10; p\u200a=\u200a0.020).']
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['It was well known that tangential vitreoretinal traction and epiretinal membrane play important roles during the formation of macular hole (MH) associated with retinal detachment (RD) in highly myopic eyes. But it was not clear about the correlations between anteroposterior traction, posterior vitreous cortex (PVC) and MH-RD. The vitreous status in highly myopic eyes were analyzed to explore the effect of PVC in the role of MH-RD formation.', 'Sixteen consecutive highly myopic eyes with RD due to MH were retrospectively analyzed from January 2009 to April 2009. The preoperative examinations for detecting posterior vitreous detachment (PVD) and vitreoretinal traction included B-mode ultrasonography and optical coherence tomography (OCT). The residual PVC and PVD were confirmed intraoperatively during triamcinolone acetonide (TA) assisted vitrectomy.', 'Under ultrasonography, the preoperative PVD patterns were stratified as: complete PVD in three (19%) eyes, partial PVD in eight (50%) eyes, and no PVD in five (31%) eyes. OCT confirmed vitreoretinal traction and no complete PVD in 10 (63%) eyes, including anteroposterior traction in four eyes and tangential traction in six eyes. During TA-assisted vitrectomy, it was confirmed that no complete PVD existed in 16 eyes, including six eyes (38%) finally diagnosed of partial PVD, and five (31%) eyes with vitreoschisis. Anteroposterior vitreoretinal traction around MH is always in conjunction with partial PVD (67%), and high proportion (80%) of vitreoschisis is associated with tangential vitreoretinal traction. Comparing with the precision of TA staining of PVD diagnosis, the coincidence rate of ultrasonography was 69% (P = 0.02), and that of OCT was 63% (P < 0.01).']
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['To understand growth regulation of the endometrium by studying the effect of interleukin-1 beta (IL-1) on human endometrial stromal cell proliferation in vitro.', 'Endometrial stromal cells from human endometrium were separated and purified and placed in culture. Fresh and first- and sixth-passage cells were incubated with IL-1 (0.025, 0.25, and 2.5 ng/mL) for 24, 48, and 72 hours, respectively. Proliferation as a function of DNA synthesis was assessed by measuring 3H-thymidine incorporation. Experiments were then repeated in the presence of indomethacin to determine whether IL-1 effects were dependent upon prostaglandin synthesis. We evaluated overall growth by adding IL-1 to cell cultures of sixth-passage stromal cells every 3 days and by performing cell count studies.', 'Interleukin-1 beta significantly inhibited 3H-thymidine uptake in freshly explanted endometrial stromal cells at all doses in a dose-dependent manner; a 44% inhibition was seen at 2.5 ng/mL IL-1 after 72 hours of incubation. In first- and sixth-passage cells, 3H-thymidine uptake was inhibited only at intermediate and high doses of IL-1. Cell count studies showed that sixth-passage cells were significantly inhibited by IL-1 after 23 days of growth (22%; P less than .01). Adding indomethacin did not affect inhibition of growth.']
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['eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD).', 'In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7×10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3×10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4×10(-3)).']
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['Geographic range is a good indicator of extinction susceptibility in fossil marine species and higher taxa. The widely-recognized positive correlation between geographic range and taxonomic duration is typically attributed to either accumulating geographic range with age or an extinction buffering effect, whereby cosmopolitan taxa persist longer because they are reintroduced by dispersal from remote source populations after local extinction. The former hypothesis predicts that all taxa within a region should have equal probabilities of extinction regardless of global distributions while the latter predicts that cosmopolitan genera will have greater survivorship within a region than endemics within the same region. Here we test the assumption that all taxa within a region have equal likelihoods of extinction.', 'We use North American and European occurrences of marine genera from the Paleobiology Database and the areal extent of marine sedimentary cover in North America to show that endemic and cosmopolitan fossil marine genera have significantly different range-duration relationships and that broad geographic range and longevity are both predicted by regional environmental breadth. Specifically, genera that occur outside of the focal region are significantly longer lived and have larger geographic ranges and environmental breadths within the focal region than do their endemic counterparts, even after controlling for differences in sampling intensity. Analyses of the number of paleoenvironmental zones occupied by endemic and cosmopolitan genera suggest that the number of paleoenvironmental zones occupied is a key factor of geographic range that promotes genus survivorship.']
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['Salmonella enterica serovar Enteritidis (S. Enteritidis) is a human and animal pathogen that causes gastroenteritis characterized by inflammatory diarrhea and occasionally an invasive systemic infection. Salmonella pathogenicity islands (SPIs) are horizontally acquired genomic segments known to contribute to Salmonella pathogenesis. The objective of the current study was to determine the contribution of SPI-13 to S. Enteritidis pathogenesis.', 'We deleted the entire SPI-13 (∆SPI-13) from the genome of S. Enteritidis CDC_2010K_0968 strain isolated from a human patient during the 2010 egg-associated outbreak in the US. The kinetics of infection of the wild-type parent and the ∆SPI-13 were compared in orally challenged day-old chickens and streptomycin pre-treated mice. The degree of intestinal inflammation and the survival of mutant strain within the avian (HD11) and murine (RAW264.7) macrophages were also determined.', 'The deletion of the SPI-13 resulted in impaired infection kinetics of S. Enteritidis in streptomycin pre-treated mice which was characterized by significantly lower (P\xa0<\xa00.05) viable counts in the ceca, liver and spleen, impaired ability to induce intestinal inflammation and reduced survival within murine macrophages. Conversely, there were no significant differences in the infection kinetics of ∆SPI-13 in day-old chickens in any of the organs tested and the survival of ∆SPI-13 within chicken macrophages remained unaltered.']
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['Neutral small hydrophiles are permeable to varying degrees, across the aqueous pores of phospholipid bilayer protein channels, with their potential for permeation into cells being predictable, on the basis of hydrophilicity and size. Here, it is hypothesized that permeation thresholds for small hydrophiles, across capillary zona occludens tight junction and inter-epithelial junction pore complexes are predictable, on the basis of predicted hydrophilicity in context of predicted molecular size and charge distribution, as are those of cations and anions, on the basis of predicted ionization in context of predicted atomic size.', 'Small hydrophiles are categorized by charge distribution. 2-dimensional plots of predicted hydrophilic octanol-to-water partition coefficient (HOWPC; unitless) and predicted van der Waals diameter (vdWD; nm) are generated for each category. The predicted HOWPC-to-vdWD ratio (nm (-1) ), and vdWDs for permeable hydrophile at the maximum and minimum HOWPC-to-vdWD, vdWD @ MAXimum HOWPC-to-vdWD and vdWD @ MINimum HOWPC-to-vdWD are determined. For cations and anions, the ionization-to-atomic diameter ratios (CI or AI-to-AD ratios; nm(-1)) are determined.', 'Per sizes of mixed and pure polyneutral hydrophiles, the permeation size maximum for hydrophiles across tight junction pore complexes is >0.69 ≤ 0.73 nanometers and across inter-epithelial junction pore complexes is ≥ 0.81 nanometers. For hydrophiles with anionicity or cationicity, the vdWDs @ MAXimum HOWPC-to-vdWD are less than those of mixed and polyneutral hydrophiles across both tight and inter-epithelial junctions, ranges specific to category and junction type. For cations, the permeation threshold across tight junctions is between the CI-to-AD ratio of Na+ (+2.69 nm(-1)) and CH3-Hg+ (+2.36 nm(-1)), with CH3-Hg+ and K+ (+2.20 nm(-1)) being permeable; and for divalent cations, the threshold across inter-epithelial junctions is between the CI-to-AD ratio of Mg2+ (+6.25 nm(-1)) and Ca2+ (+5.08 nm(-1)) , Ca2+ being semi-permeable. For anions, the permeation threshold across tight junctions is between the AI-to-AD ratio of Cl- (-4.91 nm(-1)) and Br- (-4.17 nm(-1)), and the threshold across inter-epithelial junctions is between the AI-to-AD ratio of F- (-7.81 nm(-1)) and Cl- (-4.91 nm(-1)).']
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['The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response. Certain stimulators of innate immunity (CpG DNA or GM-CSF) are reported to be anti-inflammatory in IBD. Toll-like receptor-7 (TLR7) is an important regulator of innate immunity and its activation plays a key role in induction of type I interferon (IFN). The present study tests the hypothesis that the TLR7 agonists Imiquimod has therapeutic efficacy in IBD.', 'Acute colitis was induced in Balb/c mice by giving 5% dextran sodium sulfate (DSS) in drinking water for 7 days. Mice were treated with Imiquimod either orally or topically and its therapeutic effects on disease activity were examined. Isolated mouse CD11c+ dendritic cells and human intestinal epithelial cells (HT29, HCT116) were treated with Imiquimod (10 μg/mL) and their susceptibility to intracellular Salmonella typhimurium infection was assessed by gentamicin protection assay.', 'Oral administration of Imiquimod induced type I IFN expression in the gastrointestinal mucosa and ameliorated DSS-induced acute colitis as assessed by clinical parameters, histology, and mRNA expression of proinflammatory cytokines. Topical administration of Imiquimod also ameliorated DSS colitis by inducing the expression of type I IFN in the colonic mucosa. However, no evidence for a systemic IFN response was observed. Imiquimod treatments to both CD11c+ and intestinal epithelial cells significantly increased expression of antimicrobial peptides (AMPs) and reduced survival of intracellular S. typhimurium.']
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['AMPK was shown to negatively regulate FcεRI activation, and FcεR-mediated Fyn activation can counteract the LKB1/AMPK axis in mast cells. However, the relationship between the major Src family kinase Lyn and AMPK remains poorly defined. Here, we investigate the molecular mechanism for AMPK inhibition by FcεRI-Lyn signaling in rat RBL-2H3 cells. We found that FcεRI activation could rapidly inhibit AMPK activation through increased AMPK phosphorylation at the inhibitory Ser485/491 residues without a change at the activating Th172 residue, and this was accompanied by a reduction of ACC phosphorylation. Using specific inhibitors and gene silencing, we found that such AMPK inhibition involved a signaling cascade through Lyn-Syk-Akt. When AMPK was activated by AICAR, A769662 and metformin, FcεRI-mediated Syk, ERK, JNK and p38 activation, and TNFα release were all inhibited. Consistently, AMPK inhibition by compound C increased FcεRI-mediated Lyn activation. Moreover, AMPK activation dominantly impaired IgE-induced recruitment of signal proteins to the FcεRI by blocking the formation of FcεRIβ-Lyn-Syk, FcεRIγ-Lyn-Syk, and AMPK-FcεRIβ complexes. In vitro kinase assay further revealed the ability of AMPKα2 to phosphorylate FcεRIβ in the complex. In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE. In summary, our findings demonstrate that IgE-mediated FcεRI activation results in AMPK inhibition through activation of Lyn-Syk-Akt pathway, and as such FcεRI receptor can efficiently propagate Lyn-mediated allergic signaling and response. These results provide important insights into the use of AMPK activators for the treatment of allergic diseases.']
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['In the setting of non-ST-segment-elevation (NSTE) acute coronary syndromes (ACS), the pathophysiological mechanisms underlying post-percutaneous coronary intervention (PCI) cardiac troponin I (cTnI) elevation remain unclear.', 'We evaluated the relationship between troponin elevation and tissue-level perfusion using the TIMI flow grade, corrected TIMI frame count, TIMI myocardial perfusion grade (TMPG), and myocardial contrast enhancement by intracoronary myocardial contrast echocardiography (MCE) before and immediately after PCI performed within 24 to 48 hours of hospital admission in 42 high-risk (angina at rest, unequivocal ST-segment depression, and cTnI elevation) patients with NSTE-ACS. All patients were treated with glycoprotein IIb/IIIa inhibitors (27 with tirofiban and 15 with abciximab) and had successful PCI. Fourteen patients had a postprocedural cTnI elevation, whereas 28 did not. TMPG 0/1 after PCI was observed more frequently in patients with postprocedural cTnI elevation (43% versus 7%; P<0.02). cTnI levels were higher among patients with TMPG 0/1 versus patients with TMPG 2/3 (5.3+/-2.7 versus 1.5+/-1.3 ng/mL; P<0.0001). Patients with postprocedural cTnI elevation also presented a significantly lower number of perfused segments at MCE (59% versus 81%; P=0.02) as well as a lower MCE score index (0.65+/-0.38 versus 0.89+/-0.21; P<0.02).']
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['Few data on xenon computed tomography-based quantitative cerebral blood flow (CBF) in spontaneous intracerebral hemorrhage have been reported. We correlated perihematomal CBF in a retrospective series of 42 subacute spontaneous intracerebral hemorrhage patients undergoing xenon computed tomography with in-hospital discharge status and mortality.', 'We calculated 3 area-weighted mean CBF values: (1) within the computed tomography-visible rim of perihematomal edema, (2) within a 1-cm marginal radius around the hematoma, and (3) all cortical regions of interest immediately adjacent to the hematoma. Primary outcomes were in-hospital mortality and discharge status (ordinally as 0=home, 1=acute rehabilitation, 2=nursing home, 3=death). Discharge status was used as a surrogate for in-hospital functional outcome.', 'Median hematoma volume was 14.4 cm(3) (range, 2 to 70). Median perihematomal (low-attenuation rim) CBF was 21.9 cm(3).100 g(-1).min(-1) (range, 6.1 to 81.1), and the median 1-cm marginal radius CBF was 26.8 cm(3).100 g(-1).min(-1) (range, 10.8 to 72.8). The median regional cortical CBF was 26.7 cm(3).100 g(-1).min(-1) (range, 6.9 to 72.6). Eight patients had 1-cm marginal radius or regional cortical CBF values <20 cm(3).100 g(-1).min(-1). Hematoma volume (odds ratio [OR], 1.68 per 10-cm(3) volume; P=0.036) and intraventricular hemorrhage (OR, 1.88 per grade of intraventricular hemorrhage; P=0.036) predicted mortality. Two CBF measures, hydrocephalus, and IVH predicted poor in-hospital functional outcome in bivariate analysis. Each CBF measure (OR, 0.34 to 0.43; P<0.001 to 0.003) and intraventricular hemorrhage (OR, 3.42; P<0.001) predicted in-hospital functional outcome in multivariable analyses.']
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['To assess the clinical response to interleukin-1 (IL-1) blockade and in vitro IL-1beta and IL-18 secretion in patients with systemic-onset juvenile idiopathic arthritis (JIA).', 'Twenty-two patients with systemic-onset JIA were treated with the IL-1 receptor antagonist (IL-1Ra) anakinra. Monocytes from 18 patients and 20 healthy donors were activated by different Toll-like receptor ligands. Intracellular and secreted IL-1beta and IL-18 were analyzed by Western blotting and enzyme-linked immunosorbent assay.', 'Ten patients with systemic-onset JIA exhibited a dramatic response to anakinra and were classified as complete responders. Eleven patients had an incomplete response or no response, and 1 patient could not be classified in terms of response. Compared with patients who had an incomplete response or no response, complete responders had a lower number of active joints (P = 0.02) and an increased absolute neutrophil count (P = 0.02). In vitro IL-1beta and IL-18 secretion in response to various stimuli was not increased and was independent of treatment efficacy. Likewise, secretion of IL-1Ra by monocytes from patients with systemic-onset JIA was not impaired. An overall low level of IL-1beta secretion upon exposure to exogenous ATP was observed, unrelated to treatment responsiveness or disease activity.']
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['Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) lower the risk of colorectal cancer (CRC). We investigated whether plasma inflammatory markers were associated with risk of CRC and if use of anti-inflammatory drugs was differentially associated with risk of CRC according to levels of inflammatory markers.', 'We measured levels of high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, and the soluble tumor necrosis factor receptor 2 (sTNFR-2) in blood samples from 32,826 women, collected from 1989 to 1990. Through 2004, we documented 280 cases of incident CRC; each case was matched for age to 2 randomly selected participants without cancer (controls). Information on anti-inflammatory drug (aspirin and NSAIDs) use was collected biennially.', 'Compared with women in the lowest quartile of plasma levels of sTNFR-2, women in the highest quartile had an increased risk of CRC (multivariate relative risk [RR], 1.67; 95% confidence interval [CI], 1.05-2.68; P for trend = .03). Among women with high baseline levels of sTNFR-2, those who initiated aspirin/NSAID use after blood collection had significant reductions in subsequent risk of CRC (multivariate RR, 0.39; 95% CI, 0.18-0.86). In contrast, among women with low baseline levels of sTNFR-2, initiation of aspirin/NSAID use was not associated with significant risk reduction (multivariate RR, 0.86; 95% CI, 0.41-1.79). Plasma levels of CRP and IL-6 were not significantly associated with CRC risk.']
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['Plasmacytoid dendritic cells (pDCs) constitutively express two members of the Toll-like receptor (TLR) family, TLR-9 and TLR-7, through which they can be stimulated to produce high levels of interferon (IFN)-α, a key mediator of the pathogenesis of systemic lupus erythematosus (SLE). Given the known efficacy of hydroxychloroquine (HCQ) in the treatment of SLE, we examined its ability to inhibit such pDC function in vivo.', 'Peripheral blood mononuclear cells (PBMCs) from SLE subjects treated or not with HCQ and from healthy controls were stimulated with the TLR-9 agonist, CpG oligodeoxynucleotides (CpG-A ODN)-2216, and the TLR-7 agonist, imiquimod. The proportion of monocytes, B cells, myeloid dendritic cells, pDCs, and natural killer (NK) cells producing IFN-α and tumor necrosis factor alpha (TNF-α) was then analyzed by multiparameter flow cytometry.', 'After TLR-9/7 stimulation in both SLE and healthy subjects, significant production of IFN-α and TNF-α was only observed in pDCs. TLR-7 and TLR-9 induced IFN-α and TNF-α production by pDCs from subjects with SLE was decreased relative to that found in controls (TLR-9/IFN-α, P < 0.0001; TLR-9/TNF-α P < 0.0001; TLR-7/TNF-α P = 0.01). TLR-9 and TLR-7 induced IFN-α and TNF-α production by pDCs was severely impaired in 36% (TLR-9) and 33% (TLR-7) of SLE subjects. In almost all cases, these subjects were being treated with HCQ (HCQ vs. no HCQ: impaired TLR-9/IFN-α, P = 0.0003; impaired TLR-7/IFN-α, P = 0.07; impaired TLR-9/TNF-α, P < 0.009; impaired TLR-7/TNF-α, P < 0.01).']
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['To study the abnormal cytokeratin (CK) expression, emergence of CK19 with or without CK7, in liver parenchymal cells and the role of laminin (LN), a basement membrane protein, in this process.', 'Six hepatocellular carcinoma (HCC) cell lines were examined for different CKs, LN and its receptor by immunocytochemistry and Western blotting. Double immunofluorescent reaction, laser-scanning confocal microscopy and an in vitro induction procedure were used to demonstrate the role of LN in regulating CK19 expression in these cells.', 'Immunoreactivities for CK8, CK18, CK7 and the receptor for LN were observed in all the six HCC cell lines examined. However, CK19 was merely found in four of the six cell lines, and was in any case associated with LN expression. Laser-scanning confocal microscopy demonstrated the concomitant presence of these two molecules in most of the positive cells. In the two HCC cell lines, originally negative for CK19, addition of LN to the culture medium resulted in an induction of CK19 in a dose-dependent manner. Both the artificially induced and the intrinsic production of CK19 were completely blocked by an antibody to LN.']
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['Parkland formula (PF) is the most often used schema for calculating intravenous resuscitation fluid requirement in burn patients. Some studies have reported that PF underestimates the fluid requirement in 45-63% of patients. The aim of this retrospective study was to analyse factors influencing first-day intravenous fluid replacement set for a targeted urinary output in severely burnt patients.', "Data of 47 patients with burn injury affecting equal or more than 15% of body surface area were retrieved from the archived files. The local intensive care protocol rendered the infusion rate of lactated Ringer's solution to achieve a urinary output of 0.5-1.0 mL/kg per hour in the first 24 h after burn trauma.", 'First-day i.v. infusion volume was significantly higher than PF preferred. In the first 24 h the hourly volume of intravenous fluid resuscitation per bodyweight per burnt surface area showed significant negative correlation to the burnt body surface area and body mass index, (r = -0.553, P < 0.001; r = -0.570, P < 0.001, respectively) no correlation was found to bodyweight, height or patient age. Patients having deep-burn injury required higher intravenous fluid resuscitation rate than patients having superficial injury only (P < 0.01).']
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['Cardiac-specific risks and complications after a Ladd procedure in patients with heterotaxy syndrome (HS) and intestinal rotational anomalies (IRA) are unknown. We sought to (1) describe rates of hospital mortality and early systemic-to-pulmonary (S-P) artery shunt failure after the Ladd procedure in patients with HS and (2) explore risk factors associated with early shunt failure in patients with HS with single ventricle (SV).', 'This retrospective study included all Ladd procedures performed from January 1999 to December 2012 in patients with HS at a single center. Risk factors investigated for early S-P artery shunt failure included birth weight, gestational age, sex, age at and timing of Ladd procedure relative to cardiac operations, and shunt\xa0type.', 'Ladd procedure was performed on 54 infants with HS and congenital heart disease. Hospital mortality for the entire cohort was 5.6% (3 of 54 patients). Early shunt failure occurred in 19% (4 of 21) of HS infants with SV. Mean preoperative blood urea nitrogen (BUN) levels were higher in HS infants with early shunt failure (20 versus 12.5 mg/dL; p\xa0= 0.054).']
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['To test whether signal transduction proteins that mediate stress may be used to detect responses of embryos to different media in a prospective randomized study.', 'Controlled laboratory study.', 'None.', 'None.', 'Mouse embryos isolated at E3.5 (3.5 days after fertilization) or E1.5 were cultured in different media for 24 hours or 72 hours, respectively. Expression of p38 mitogen activated protein kinases (MAPKs) and stress-activated protein kinase/Jun kinase (SAPK/JNK) phosphoproteins in the mouse embryo and their correlation with preimplantation development were studied.', "[1] In E3.5 embryos, SAPK/JNK and p38MAPK are phosphorylated at different levels in different media after 24 hours, with Ham's F10+BSA and M-16 having the highest intensity of both SAPK/JNK and p38MAPK phosphorylation and Quinn's cleavage medium and potassium simplex optimized medium supplemented with amino acids (KSOM+AA) the lowest intensity. [2] The stress-induced increase in phosphorylation of SAPK/JNK and p38MAPK appears to be post-translational in embryos. [3] The intensity of SAPK/JNK phosphorylation measured at E1.5+72 hours culture is inversely correlated with 4-cell/compaction rate, morula formation rate, blastocyst formation rate, and hatching rate.", 'SAPK/JNK and p38MAPK phosphoprotein levels, but not all forms of protein, are affected during culture of preimplantation embryos in seven different media. During culture, the rate of progress to four developmental events was assayed and each rate was inversely proportional to the level of SAPK/JNK phosphorylation measured by immunocytochemical means or Western blot analysis at the end of culture.']
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['Stavudine (d4T), a nucleoside reverse-transcriptase inhibitor (NRTI), can induce lipoatrophy, fatty liver, hyperlactataemia and abnormal liver tests. NRTI toxicity is usually ascribed to mitochondrial DNA (mtDNA) depletion and impaired mitochondrial respiration. However, NRTIs could have effects unrelated to mtDNA. Recently, we reported that 100 mg/kg/day of d4T stimulated fatty acid oxidation (FAO) in mouse liver, and reduced body fatness without depleting white adipose tissue (WAT) mtDNA. We hypothesized that higher d4T doses could further reduce adiposity, while inhibiting hepatic FAO.', 'Mice were treated for 2 weeks with d4T (500 mg/kg/day), L-carnitine (200 mg/kg/day) or both drugs concomitantly. Body fatness was assessed by dual energy X-ray absorptiometry, and investigations were performed in plasma, liver, muscle and WAT.', 'D4T reduced the gain of body adiposity, WAT leptin, whole body FAO and plasma ketone bodies, and increased liver triglycerides and plasma aminotransferases with mild ultrastructural abnormalities in hepatocytes. Plasma lactate and respiratory chain activities in tissues were unchanged. Stearoyl-CoA desaturase (SCD-1), an enzyme negatively regulated by leptin, was overexpressed in liver. High doses of beta-aminoisobutyric acid (BAIBA), a d4T catabolite, increased plasma ketone bodies. Although L-carnitine did not correct body adiposity, it prevented d4T-induced impairment of FAO and liver abnormalities.']
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['The human APOBEC3G (A3G) protein activity is associated with innate immunity against HIV-1 by inducing high rates of guanosines to adenosines (G-to-A) mutations (viz., hypermutation) in the viral DNA. If hypermutation is not enough to disrupt the reading frames of viral genes, it may likely increase the HIV-1 diversity. To counteract host innate immunity HIV-1 encodes the Vif protein that binds A3G protein and form complexes to be degraded by cellular proteolysis.', 'Here we studied the pattern of substitutions in the vif gene and its association with clinical status of HIV-1 infected individuals. To perform the study, unique vif gene sequences were generated from 400 antiretroviral-naïve individuals.', 'The codon pairs: 78-154, 85-154, 101-157, 105-157, and 105-176 of vif gene were associated with CD4+ T cell count lower than 500 cells per mm(3). Some of these codons were located in the (81)LGQGVSIEW(89) region and within the BC-Box. We also identified codons under positive selection clustered in the N-terminal region of Vif protein, between (21)WKSLVK(26) and (40)YRHHY(44) regions (i.e., 31, 33, 37, 39), within the BC-Box (i.e., 155, 159) and the Cullin5-Box (i.e., 168) of vif gene. All these regions are involved in the Vif-induced degradation of A3G/F complexes and the N-terminal of Vif protein binds to viral and cellular RNA.']
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['To evaluate the efficacy of a lifestyle intervention programme including meal replacements and increased physical activity upon body weight, diabetes control and other cardiovascular risk factors in obese, poorly controlled, insulin-treated, type-2-diabetic individuals and to assess the impact of concomitant rosiglitazone (RSG) therapy.', 'This 6-month intervention study included 21 patients with type 2 diabetes mellitus (DM) requiring insulin therapy with haemoglobin A1c (HbA1c) > 7% and with a body mass index (b.m.i.) > 27. All subjects were enrolled in a 6-month lifestyle intervention programme and randomized to placebo or RSG 4 mg/day. Participation in the lifestyle programme included meal replacements, increased intake of fruits and vegetables and increased daily physical activity. Measured end-points included body weight, waist circumference, blood pressure, HbA1c and serum lipids, before entry into the study.', 'The baseline mean b.m.i. was 36.4 and the mean HbA1c was 9.0%. The greatest weight losses occurred during the first 12 weeks (19 lbs for RSG, 13.4 lbs for placebo) with a greater weight loss at each point for the group receiving RSG. Waist circumference declined by 2.8 and 4.0 inches for the placebo and RSG groups. Systolic BP declined 16.2 mmHg in the placebo group and 14.3 mmHg in the RSG group. Diastolic blood pressure decreased by 12.8 mmHg in the placebo group. HbA1c was reduced significantly by 1.3% for the placebo group and 1.1% in the RSG group.']
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['C-reactive protein (CRP) inhibits the activity of the endothelial isoform of nitric oxide synthase (eNOS) via uncoupling of the enzyme both in vitro and in vivo. eNOS activity appears to be related in part to its interaction with other cellular proteins, including heat shock protein 90 (Hsp90), caveolin-1, and porin. In this study, we examined the effect of CRP treatment of human aortic endothelial cells (HAECs) on eNOS interaction with caveolin-1, Hsp90, and porin.', 'We incubated HAECs with CRP (0, 12.5, and 25 mg/L) for 1, 6, or 24 h and assessed the interaction of these proteins with eNOS by immunoprecipitation and western blotting.', 'CRP treatment (12.5 and 25 mg/L) of HAECs for 24 h significantly increased eNOS binding to caveolin-1 (40% and 54% increase, respectively; P < 0.05) and decreased binding to Hsp90 (33% and 66% decrease, respectively; P < 0.05). CRP (25 mg/L) also significantly decreased the binding of porin to eNOS (11% decrease, P < 0.05). Similar results were seen when HAECs were treated with CRP for 6 h.']
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["The reasons why patients decide to consult a general practitioner vary enormously. While there may be individual reasons for this variation, the family context has a significant and unique influence upon the frequency of individuals' visits. The objective of this study was to explore which family factors can explain the differences between strikingly high, and correspondingly low, family consultation rates in families with children aged up to 21.", "Data were used from the second Dutch national survey of general practice. This survey extracted from the medical records of 96 practices in the Netherlands, information on all consultations with patients during 2001. We defined, through multilevel analysis, two groups of families. These had respectively, predominantly high, and low, contact frequencies due to a significant family influence upon the frequency of the individual's first contacts. Binomial logistic regression analyses were used to analyse which of the family factors, related to shared circumstances and socialisation conditions, can explain the differences in consultation rates between the two groups of families.", "In almost 3% of all families, individual consultation rates decrease significantly due to family influence. In 11% of the families, individual consultation rates significantly increase due to family influence. While taking into account the health status of family members, family factors can explain family consultation rates. These factors include circumstances such as their economic status and number of children, as well as socialisation conditions such as specific health knowledge and family beliefs. The chance of significant low frequencies of contact due to family influences increases significantly with factors such as, paid employment of parents in the health care sector, low expectations of general practitioners' care for minor ailments and a western cultural background."]
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['The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.', 'To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8\xa0weeks.', 'CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak αSMA staining. Furthermore, PCR analysis demonstrated that TGF-β and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.']
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['To test the hypothesis that peninsular Arabs and South Asians share a tendency to insulin resistance, differing from other ethnic groups living in the United Arab Emirates (UAE).', 'A representative sample of 358 apparently healthy men aged 35-49 years drawn from a multiethnic office-based workforce in the UAE was tested. The sample included a reference group of expatriate South Asians, in whom insulin resistance has already been described as the cause of high coronary heart disease (CHD) mortality. All subjects were screened for CHD risk factors, including glucose tolerance and 2-h serum insulin determinations.', 'There was a high prevalence of previously undiagnosed cases of diabetes (10.1%) and hypertension (14.2%). South Asian and peninsular Arab men shared the tendency to significantly higher 2-h glucose and insulin levels, lower HDL cholesterol concentrations and abdominal obesity especially compared to Europeans, who were five times less likely to be glucose-intolerant (OR 5.40, P = 0.015). Three other Arab groups were intermediate in most trends.']
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['Thlaspi caerulescens is a natural selected heavy metal hyperaccumulator that can not only tolerate but also accumulate extremely high levels of heavy metals in the shoots. Thus, to identify the transportors involved in metal long-distance transportation is very important for understanding the mechanism of heavy metal accumulation in this hyperaccumulator.', 'We cloned and characterized a novel gene TcOPT3 of OPT family from T. caerulescens. TcOPT3 was pronouncedly expressed in aerial parts, including stem and leaf. Moreover, in situ hybridization analyses showed that TcOPT3 expressed in the plant vascular systems, especially in the pericycle cells that may be involved in the long-distance transportation. The expression of TcOPT3 was highly induced by iron (Fe) and zinc (Zn) deficiency, especially in the stem and leaf. Sub-cellular localization showed that TcOPT3 was a plasma membrane-localized protein. Furthermore, heterogonous expression of TcOPT3 by mutant yeast (Saccharomyces cerevisiae) complementation experiments demonstrated that TcOPT3 could transport Fe(2+) and Zn(2+). Moreover, expression of TcOPT3 in yeast increased metal (Fe, Zn, Cu and Cd) accumulation and resulted in an increased sensitivity to cadmium (Cd) and copper (Cu).']
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['Prolonged chest compression interruptions immediately preceding and following a defibrillation shock reduce shock success and survival after cardiac arrest. We tested the hypothesis that compression pauses would be shorter using an AED equipped with a new Analysis during Compressions with Fast Reconfirmation (ADC-FR) technology, which features automated rhythm analysis and charging during compressions with brief reconfirmation analysis during compression pause, compared with standard AED mode.', 'BLS-certified emergency medical technicians (EMTs) worked in pairs and performed two trials of simulated cardiac resuscitation with a chest compression sensing X Series defibrillator (ZOLL Medical). Each pair was randomized to perform a trial of eight 2-min compression intervals (randomly assigned to receive four shockable and four non-shockable rhythms) with the defibrillator in standard AED mode and another trial in ADC-FR mode. Subjects were advised to follow defibrillator prompts, defibrillate if "shock advised," and switch compressors every two intervals. Compression quality data were reviewed using RescueNet Code Review (ZOLL Medical) and analyzed using paired t-tests.', 'Thirty-two EMT-basic prehospital providers (59% male; median 25 years age [IQR 22-27]) participated in the study. End of interval compression interruptions were significantly reduced with ADC-FR vs. AED mode (p<0.001). For shockable rhythms, pre-shock pause was reduced significantly with ADC-FR compared with AED use (7.35±0.16s vs. 12.0±0.22s, p<0.001) whereas post-shock pause was similar (2.08±0.14s vs. 1.77±0.14s, p=0.1).']
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['Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown.', 'In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis.']
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['A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes.', 'This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation.', 'Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes.', 'The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest.']
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['Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied.', 'We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens.', 'Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-γ (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed.', 'Three previously identified dominant T cell epitopes (Amb a 1 176-191, 200-215, and 344-359) were confirmed, and three novel dominant epitopes (Amb a 1 280-295, 304-319, and 320-335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens.']
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['Although many hypotheses regarding the pathogenesis of polycystic ovary syndrome (PCOS) have been generated, genetic studies have not identified specific genes that play a role in PCOS etiopathogenesis. This study aimed to investigate the relationship between TGF-β1 gene polymorphism and PCOS in Koreans.', 'A total of 51 Korean women with PCOS and 69 healthy women were enrolled. We analyzed 4 single nucleotide polymorphisms (SNPs) of the TGF-β1 gene (rs11466313, rs1800469, rs2317130, and rs4803457). We also analyzed laboratory measurements, such as free testosterone, glucose, and cholesterol.', 'The frequencies of rs1800469T allele negativity, rs4803457T allele negativity, the rs1800469CC genotype, and the rs4803457CC genotype showed positive associations with PCOS (P\u2009=\u20090.003, P\u2009=\u20090.027, P\u2009=\u20090.009, and P=0.031, respectively), whereas the haplotypes rs1800469C-rs4803457T and rs1800469T-rs4803457T showed negative associations with PCOS. A strong protective effect of the "rs1800469CT-rs4803457TT" combination (OR\u2009=\u20090.09) and a strong risk effect of "rs1800469CC-rs4803457CC" (OR\u2009=\u20096.23) for PCOS were observed. The rs1800469C/T and rs2317130C/T SNPs exhibited associations with several laboratory measurements with various levels of significance.']
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['The association of MR imaging abnormalities with clinical disability in multiple sclerosis (MS) has been disappointing. This association might be improved by imaging specific functional systems in the central nervous system-for example, the motor system in a patient with weakness. Our aim was to assess the relationship between muscle strength in MS and corticospinal tract (CST) abnormalities detected with multimodality MR imaging of the brain.', 'In 47 individuals with MS, diffusion tensor imaging (DTI) at 3T was used to reconstruct the intracranial CSTs. Tract profiles depicted the variation in T2 relaxation time, magnetization transfer ratio (MTR), and DTI-derived indices (fractional anisotropy and diffusivity) as a function of normalized position along the tract. Brain parenchymal fraction was calculated as a normalized measure of brain volume. Stepwise linear regression modeling was used to determine the MR imaging indices most closely related to ankle dorsiflexion and hip flexion strength assessed with quantitative dynamometry.', 'Individuals with MS were significantly weak: Average ankle strength fell 1.7 SDs below the age-, handedness-, and sex-corrected healthy mean. Brain parenchymal fraction was not associated with weakness. A parsimonious model that includes MTR in the brain stem and MS clinical subtype explained 30%-45% of the variance in ankle and hip strength. The model was successfully applied to scans and strength data from the same individuals at an earlier time point.']
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['To determine the effect of a Nutrition and Exercise Lifestyle Intervention Program (NELIP) for overweight (OW) and obese (OB) pregnant women on pregnancy weight gain, birth weight, and maternal weight retention at 2 months postpartum.', 'This is a single-arm intervention matched by prepregnant body mass index, age, and parity to a historical cohort (4:1). Women with a prepregnancy body mass index of > or = 25.0 kg x m(-2) (N = 65) participated in a NELIP starting at 16-20 wk of pregnancy, continuing until delivery. NELIP consisted of an individualized nutrition plan with total energy intake of approximately 2000 kcal x d(-1) (8360 kJ x d(-1)) and 40%-55% of total energy intake from carbohydrate. Exercise consisted of a walking program (30% HR reserve), three to four times per week, using a pedometer to count steps. Matched historical cohort (MC; N = 260) was from a large local perinatal database.', 'Weight gained by women on the NELIP was 6.8 +/- 4.1 kg (0.38 +/- 0.2 kg x wk(-1)), with a total pregnancy weight gain of 12.0 +/- 5.7 kg. Excessive weight gain occurred before NELIP began at 16 wk of gestation. Eighty percent of the women did not exceed recommended pregnancy weight gain on NELIP. Weight retention at 2 months postpartum was 2.2 +/- 5.6 kg with no difference between the OW and the OB women on NELIP. Mean birth weight was not different between NELIP (3.59 +/- 0.5 kg) and MC (3.56 +/- 0.6 kg, P > 0.05).']
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['Irritable bowel syndrome (IBS) is one of the most common disorders seen by gastroenterologists. Visceral hypersensitivity is now well recognized as a clinical marker for the disease. Intrarectal lidocaine has been previously shown to decrease pain report from rectal distension in patients with IBS without any significant serum lidocaine levels. We conducted a prospective, double-blind, crossover trial on 10 patients with IBS to evaluate the effects of 300 mg intrarectal lidocaine jelly on abdominal pain. Ten Caucasian premenopausal women who met the Rome II criteria for diarrhea-predominant IBS were recruited into the study. All of the patients that participated had intermittent left lower quadrant pain and diarrhea. Each patient participated in 2 sessions in which saline jelly (placebo) and lidocaine jelly was administered on a double-blind, crossover basis. Patients participated in these sessions at a time when their ongoing pain was at least 3 on a 0 to 10 visual analogue scale. In comparison to placebo saline jelly, lidocaine jelly significantly decreased abdominal pain (P < .02) for at least 4 hours. None of the patients experienced any side effects. Intrarectal lidocaine may be a potentially useful treatment for chronic abdominal pain in IBS.']
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['Serum soluble urokinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent focal segmental glomerulosclerosis (FSGS). It is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases that can differentiate FSGS and other glomerular diseases.', 'We measured the serum soluble urokinase receptor levels and determined their association with clinical and pathologic data in 86 patients with primary FSGS, 5 repeat renal biopsy FSGS, and 6 recurrent FSGS post-transplantation. Healthy controls and patients with minimal change disease and membranous nephropathy were used as controls. The suPAR levels were measured by commercial enzyme-linked immunosorbent assay kits.', 'Patients with primary FSGS (median: 4232, interquartile range 1299-9714 pg/mL) had significantly higher levels of suPAR than those of patients with minimal change disease (median: 2784 pg/mL), membranous nephropathy (median: 3478 pg/mL), and healthy individuals (median: 1994 pg/mL). There was no significant difference in suPAR levels between the 65 patients with minimal change disease and 85 patients with membranous nephropathy. The suPAR levels increased in the 5 repeated renal biopsy FSGS and 6 recurrent FSGS post-transplantation.']
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['The newly identified metastasis-associated in colon cancer-1 (MACC1) gene is involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), invasiveness, and metastasis in a variety of malignancies. Overexpression of MACC1 gene is a prognostic marker for poor outcome of hepatocellular carcinoma (HCC) patients. However, the association between genetic polymorphisms of MACC1 gene and poor outcome in HCC has been not been performed. We therefore investigated the correlation of MACC1 single nucleotide polymorphisms (SNPs) with tumor recurrence and overall survival in HCC patients undergoing liver transplantation (LT).', 'The study included 187 HCC patients treated with LT. Five polymorphisms in the MACC1 gene (rs1990172, rs3735615, rs4721888, rs2241056, rs975263) were genotyped in 183 cases of tumorous tissue sample and 117 cases of adjacent normal tissue sample using SNaP-Shot assays. The association of SNPs with tumor recurrence and overall survival was then analyzed by additive, dominant, recessive, and overdominant models in a cohort of 156 HCC patients.', 'In terms of tumor recurrence, heterozygous of SNP rs1990172 and SNP rs975263 showed a significant high risk of relapse using univariate and multivariate analysis (overdominant, HR(95%CI)=2.27 [1.41-3.66], P=0.001; HR(95%CI)=2.16 [1.37-3.39], P=0.001). But the difference between heterozygous of these two SNPs and overall survival did not reach a significance in all models. The other three investigated SNPs were not significantly associated with tumor recurrence and overall survival (P>0.05). In addition, we found no significant difference in genotype frequencies between HCC and controls.']
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['The relationship between physician case volume and patient outcome in patients with head and neck cancers such as nasopharyngeal carcinoma treated by radiotherapy is unknown. This study was designed to investigate the association between the case volume of radiation oncologists and the survival of patients with nasopharyngeal carcinoma.', 'Retrospective cohort study.', 'Based on nationwide claims data (National Health Research Insurance Database) in the years 2002-2008.', 'Newly diagnosed patients with nasopharyngeal carcinoma receiving curative radiotherapy in the year 2003.', 'Overall survival until 2008. We used the running log-rank test to decide the optimal threshold for categorising the case volume of radiation oncologists. The characteristics of patients, their treatments and contact with health service providers were considered as co-explanatory variables. The log-rank test and Cox regression were performed. Sensitivity analyses were carried out regarding major study assumptions.', 'Five hundred and sixty-two patients with nasopharyngeal carcinoma newly diagnosed in 2003 were identified as the study cohort. The 5-year overall survival was better among patients treated by high-volume (≥6 patients in year 2002) radiation oncologists than by low-volume (<6 patients in year 2002) radiation oncologists (77%versus 64%, P = 0.0007). The adjusted hazard ratio of death was 0.65 (95% confidence interval, 0.48-0.91) upon multivariate analysis. Patients aged at least 65 years also had a lower survival rate than those younger than 65 years old (adjusted hazard ratio of death: 2.81, 95% confidence interval: 1.94-4.08).The physician case volume and patient outcome effect remained the same after sensitivity analyses.']
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['This review will discuss the recent advances in the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy (ARVC).', 'Since the first detailed clinical description of the disease in 1982, we have learned much about the genetics, pathophysiology, diagnosis, and management of ARVC. We now appreciate that pathogenic mutations in desmosomal genes are the most common genetic finding. Although the right ventricle is mostly affected, left ventricular involvement is being increasingly recognized. Electrical instability precipitating sudden cardiac death often presents before structural abnormalities, and therefore early accurate diagnosis is of utmost importance. The broad spectrum of phenotypic variation, age-related penetrance, and lack of a definitive diagnostic test make the clinical diagnosis challenging. The diagnosis is made by fulfilling the 2010 Task Force criteria. Today, genetic testing and cardiac MRI play an important role in the diagnosis. Implantable cardioverter defibrillator implantation is the only lifesaving therapy available today for a subset of patients. In patients with recurrent ventricular arrhythmias, epicardial catheter ablation has demonstrated improved outcomes compared with endocardial ablation. Exercise restriction may delay the progression of disease.']
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['ARHGAP21 is a Rho GTPase-activating protein (RhoGAP) that associates with many proteins and modulates several cellular functions, including actin cytoskeleton rearrangement in different tissues. However, it is unknown whether ARHGAP21 is expressed in pancreatic beta cells and its function in these cells. Herein, we assess the participation of ARHGAP21 in insulin secretion.', "Neonatal mice were treated with anti-sense oligonucleotide against ARHG AP21 (AS) for 2 days, resulting in a reduction of the protein's expression of about 60% in the islets. F-actin depolimerization, insulin secretion,mRNA level of genes involved in insulin secretion, maturation and proliferation were evaluated in islets from both control and AS-treated mice.", 'ARHGAP21 co-localized with actin inMIN6 beta cells and with insulin in neonatal pancreatic islets. F-actin was reduced in AS-islets, as judged by lower phalloidin intensity. Insulin secretion was increased in islets from AS-treated mice, however no differences were observed in the GSIS (glucose-stimulated insulin secretion). In these islets, the pERK1/2 was increased, as well as the gene expressions of VAMP2 and SNAP25, proteins that are present in the secretory machinery. Maturation and cell proliferation were not affected in islets from AS-treated mice.']
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['Mycoplasma pneumoniae is a significant cause of pneumonia in humans.', 'To determine the impact of mycoplasma infection and the host inflammatory response on alveolar type II (ATII) cell ion transport in vivo and in vitro.', 'Mice were infected with M. pulmonis for measurements of alveolar fluid clearance (AFC) in vivo and isolation of ATII cells. ATII cells were infected in vivo for determination of epithelial Na+ channel (ENaC) total and cell surface protein levels by biotinylation and Western blot and in vitro for whole cell patch clamp recording and measurement of nitric oxide (NO) production by chemiluminescence.', 'Mycoplasma infection significantly inhibited AFC at 24 h and total and amiloride-sensitive AFC by 48 h postinfection (pi). In contrast, infected myeloperoxidase-deficient mice had similar basal and amiloride-sensitive AFC values to uninfected control mice at 48 h pi. Addition of forskolin restored total and amiloride-sensitive AFC to control values at 48 h pi. ATII cells isolated from infected mice demonstrated normal alpha, beta, and gamma ENaC total protein levels; however, infected whole-lung cell-surface levels of gamma ENaC were significantly decreased. Patch-clamp recordings demonstrated a significant decrease in total and amiloride-sensitive Na+ currents at 24 h pi. ATII cells demonstrated a significant increase in the production of NO at 24 h pi and inhibition of NO by ATII cells before infection reversed the decrease in total Na+ currents.']
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['Very preterm-born neonates (24-32 weeks of gestation) are exposed to stressful and painful procedures during neonatal intensive care. Analgesic and sedation therapies are essential, and opiates and benzodiazepines are commonly used. These medications may negatively impact brain development. The hippocampus may be especially vulnerable to the effects of pain and analgesic and/or sedative therapies and contribute to adverse outcomes. The effect of invasive procedures and analgesic-sedative exposure on hippocampal growth was assessed, as was that of hippocampal growth on neurodevelopmental outcome.', 'A total of 138 neonates (51% male, median gestational age = 27.7 weeks) underwent magnetic resonance imaging and diffusion tensor imaging (DTI) scans, early in life (postmenstrual age [PMA]\u2009= 32.3 weeks) and at term-equivalent age (PMA = 40.2 weeks). Volumes and DTI measures of axial diffusivity, radial diffusivity, and mean diffusivity (MD) were obtained from the hippocampus. Cognitive, language, and motor abilities were assessed using the Bayley Scales of Infant Development-III at 18.7 months median corrected age. Models testing the association of invasive procedures with hippocampal volumes and DTI measures accounted for birth gestational age, sex, PMA, dose of analgesics/sedatives (fentanyl, morphine, midazolam), mechanical ventilation, hypotension, and surgeries.', 'Total midazolam dose predicted decreased hippocampal volumes (β =\u2009-1.8, p < 0.001) and increased MD (β = 0.002, p = 0.02), whereas invasive procedures did not (β = 0, p > 0.5 each). Lower cognitive scores were associated with hippocampal growth (β =\u2009-0.31, p = 0.003), midazolam dose (β =\u2009-0.27, p = 0.03), and surgery (β =\u2009-8.32, p = 0.04).']
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['The presence of organic sulfur-containing compounds in the environment is harmful to animals and human health. The combustion of these compounds in fossil fuels tends to release sulfur dioxide in the atmosphere, which leads to acid rain, corrosion, damage to crops, and an array of other problems. The process of biodesulfurization rationally exploits the ability of certain microorganisms in the removal of sulfur prior to fuel burning, without loss of calorific value. In this sense, we hypothesized that bacterial isolates from tropical landfarm soils can demonstrate the ability to degrade dibenzothiophene (DBT), the major sulfur-containing compound present in fuels.', 'Nine bacterial isolates previously obtained from a tropical landfarm soil were tested for their ability to degrade dibenzothiophene (DBT). An isolate labeled as RR-3 has shown the best performance and was further characterized in the present study. Based on physiological aspects and 16 s rDNA sequencing, this isolate was found to be very closely related to the Bacillus pumillus species. During its growth, high levels of DBT were removed in the first 24 hours, and a rapid DBT degradation within the first hour of incubation was observed when resting cells were used. Detection of 2-hydroxybiphenyl (HBP), a marker for the 4S pathway, suggests this strain has metabolical capability for DBT desulfurization. The presence of MgSO4 in growth medium as an additional sulfur source has interfered with DBT degradation.']
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['To study the antitumor effect of anti-NprPSA monoclonal antibody (mAb) in combination with ManNPr, a precursor of N-propionyl PSA, in multiple myeloma (MM), and to explore the mechanisms of the action.', 'Human multiple myeloma cell line RPMI-8226 was tested. The cells were pre-treated with ManNPr (1, 2, and 4 mg/mL), and then incubated with anti-NprPSA mAb (1 mg/mL). Cell apoptosis in vitro was detected using MTT assay and flow cytometry. BALB/c nude mice were inoculated sc with RPC5.4 cells. On 5 d after the injection, the mice were administered sc with anti-NprPSA mAb (200 μg/d) and ManNPr (5 mg/d) for 8 d. The tumor size and body weight were monitored twice per week. TUNEL assay was used for detecting apoptosis in vivo. The apoptotic pathway involved was examined using Western blot analysis and caspase inhibitor.', 'Treatment of RPMI-8226 cells with anti-NprPSA mAb alone failed to inhibit cell growth in vitro. In RPMI-8226 cells pretreated with ManNPr, however, the mAb significantly inhibited the cell proliferation, decreased the viability, and induced apoptosis, which was associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. In the mouse xenograft model, treatment with the mAb in combination with ManNPr significantly inhibited the tumor growth, and induced significant apoptosis as compared to treatment with the mAb alone. Moreover, apoptosis induced by the mAb in vivo resulted from the activation of the caspases and poly(ADP-ribose) polymerase.']
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['Adiposity rebound (AR) is defined as the nadir or the inflexion point of body mass index (BMI) percentiles between the age of 3 and 7 years. An early rebound is seen as a risk of obesity and, thus, AR is considered as a suitable time period for prevention. As BMI does not reflect body composition, we aimed to examine the rebounds of fat mass index (FMI) and fat-free mass index (FFMI) together with BMI.', "Cross-sectional data of 19\u2009264 children aged 3-11 years were pooled from three German studies (Kiel Obesity Prevention Study, the project 'Better diet. More exercise. KINDERLEICHT-REGIONS' and regular examinations of Jena children). Height and weight were measured. Fat mass (FM) and fat-free mass (FFM) were obtained from bioelectrical impedance analysis and analysed using a population-specific algorithm. Percentiles of BMI, FMI and FFMI were constructed by the LMS method.", 'Both BMI and FMI percentiles showed a rebound, whereas FFMI percentiles steadily increased with age. On P90, FMI rebound was about 1.6-1.8 years later compared with that of BMI, that is, at ages 4.2 years (BMI) and 5.8 years (FMI) in boys and at 4.2 years (BMI) and 6.0 years (FMI) in girls. At AR, the slope of the BMI-P90 was explained by increases in FFMI rather than FMI. By contrast, at FMI rebound, the slope of BMI was strongly related to FMI.']
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['Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth. We studied simultaneously the effects of size at birth, INS and HLA genotypes on the risk of type 1 diabetes to test whether the relation between size at birth and risk of type 1 diabetes would be strengthened after adjustment for INS and HLA genotypes.', 'We designed a population-based case-control study in Norway with 471 cases of childhood-onset type 1 diabetes and 1,369 control subjects who were genotyped for the INS -23HphI polymorphism (surrogate for INS variable number of tandem repeats) and HLA-DQ alleles associated with type 1 diabetes. Data on birthweight and other perinatal factors were obtained from the Medical Birth Registry of Norway by record linkage.', 'The data fitted a multiplicative model for the protective INS class III allele both within the INS locus and for the model with INS- and HLA-DQ-conferred risk of type 1 diabetes. We found no overall significant association between weight or head circumference at birth and the risk of type 1 diabetes, and adjustment for INS and HLA genotype did not influence this result. There was also no evidence for association of INS or HLA with size at birth among control subjects.']
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['A sustained bradycardia is used as a major indicator of severe perinatal asphyxia. However, lambs asphyxiated ex utero do not exhibit the same bradycardic response as lambs asphyxiated in utero. It is possible that the local in utero environment may influence the initial cardiovascular response to asphyxia. We assessed the effect of facial immersion in water on the cardiovascular response to birth asphyxia.', "Pregnant ewes (138±1\u2005days gestation) were anaesthetised and fetuses were exteriorised and instrumented for measurement of cardiopulmonary haemodynamics. The lamb's head either remained in air (n=5) or was placed in water that was either warm (40±1°C; n=5) or at room temperature (21±1°C; n=5) before the umbilical cord was clamped to induce asphyxia.", 'Heart rate after bradycardia onset was reduced in lambs asphyxiated with their head in cool water (-34±2%) and warm water (-25±4%) compared with those in air (-11±5%; p<0.05). Similarly, the decrease in blood pressure was faster in lambs with water around the face compared with those in air. From 75\u2005s after asphyxia onset, mean and end-diastolic carotid blood flow was higher in the group asphyxiated in air (25±4\u2005mL/kg/min), compared with the groups in water (13±3\u2005mL/kg/min, warm water; 16±2\u2005mL/kg/min, cool water; p<0.05).']
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['This study was designed to develop an accurate preoperative index of prediction of outcome and hospital charges after lung resection with standard available pulmonary tests in a tertiary cancer center.', 'Sixty-one consecutive patients undergoing pulmonary resections were evaluated. All patients underwent spirometry, carbon monoxide diffusion capacity, split lung function testing, and room air blood gas analysis at rest and after a 2-minute step climb. The thoracic prospective data base and patient charts were reviewed for length of hospitalization, postoperative length of stay, and complications requiring therapy. Logistic regression analysis of the preoperative data, operation and postoperative outcome was used to develop a new postoperative predictive index: the predictive respiratory complication quotient (PRQ). We describe the design of the equation for the probability of serious pulmonary complications, hospital stay, and hospital charges based on PRQ.', 'Ten of 12 patients with a PRQ less than 2,200 suffered serious pulmonary complications of pneumonia, respiratory insufficiency, hypoxemia, and death. Forty-nine patients with a PRQ more than 2,200 did not experience any pulmonary complications. Postoperative length of stay and hospital charges correlated with the PRQ.']
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['To prospectively examine the association of major depression with incidence of the metabolic syndrome in women.', "Data were drawn from one of seven sites of the Study of Women's Health Across the Nation (SWAN), a prospective cohort study of the menopausal transition. Participants were 429 (34.5% African-American) women. Major depression and comorbid diagnoses were assessed via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders at baseline and seven annual follow-up evaluations. The metabolic syndrome was measured at baseline and each follow-up evaluation (except the second) based on National Cholesterol Education Program (NCEP) criteria.", 'Longitudinal generalized estimating equations (GEE) models indicated that, in women who were free of the metabolic syndrome at baseline, a lifetime major depression history or current major depressive episode at baseline was significantly associated with the onset and presence of the metabolic syndrome during the follow-up (odds ratio = 1.82; 95% Confidence Interval (CI) = 1.06-3.14). Survival analyses showed that, in women who were free of the metabolic syndrome at baseline, a lifetime major depression history or current major depressive episode at baseline predicted increased risk of developing the metabolic syndrome during the follow-up (hazard ratio = 1.66; 95% CI = 0.99-3.75). Lifetime history of alcohol abuse or dependence predicted incident metabolic syndrome and attenuated the association between depression and the metabolic syndrome in both models.']
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['Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed.', 'We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60\u200aml/min per 1.73 m at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination.', 'The mean age of the participants averaged 62.9\u200a±\u200a8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97-1.30] and 1.21 (95% CI 1.04-1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD.']
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['To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.', 'There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.', 'SNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).']
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['Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI.', 'This study consisted of 760 patients with AMI who were admitted within 48h after symptom onset. AKI was diagnosed as increase in creatinine ≥0.3mg/dl or ≥50% within any 48h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48h after admission) and late-AKI (>48h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI.', 'Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p<0.001) and no-AKI (3%, p<0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p=0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p<0.001). Patients with persistent early-AKI had the highest mortality (66%, p<0.001).']
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['To identify CSF biomarkers for multiple sclerosis (MS) in children with an initial acquired CNS demyelinating syndrome (ADS).', 'CSF was collected from a cohort of 39 children with initial ADS, 18 of whom were diagnosed with MS and 21 of whom had a monophasic disease course. Proteomic analysis of trypsinized CSF (20 μL) was performed by nano-liquid chromatography Orbitrap mass spectrometry. Univariate statistical analysis was used to identify differentially abundant proteins between childhood-onset MS and monophasic ADS.', 'A total of 2,260 peptides corresponding to 318 proteins were identified in the total set of samples. Of these 2,260 peptides, 88 were identified as being most distinctive between MS and ADS. Fifty-three peptides, corresponding to 14 proteins, had higher abundance in children with MS compared to children with monophasic ADS. Twelve of these 14 proteins were linked to neuronal functions and structures, such as synapses, axons, and CNS proteases (e.g., neurofascin, carboxypeptidase E, brevican core protein, and contactin-2). The other 2 were functionally related to immune function. The 35 peptides identified with decreased abundance in children with MS corresponded to 7 proteins. Six of them were linked to innate immune function (e.g., haptoglobin, haptoglobin-related protein, C4b-binding protein alpha chain, and monocyte differentiation antigen CD14) and 1 was linked to cellular adhesion (protein diaphanous homolog 1).']
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['Beta-blocker use in elective noncardiac surgery has been associated with a reduction in mortality and cardiovascular complications. Traumatic brain injury (TBI) is often associated with a hyperadrenergic state. We hypothesized that adrenergic blockade would confer improved survival among TBI patients.', 'Retrospective review of the Trauma Registry of the American College of Surgeons database at a Level I trauma center was conducted. All trauma patients admitted from January 2004 to March 2005 with head Abbreviated Injury Scale score of 3 or greater were evaluated. Patients with length of stay <4 or >30 days were excluded. Beta-blocker exposure was defined as receiving beta-blockers for 2 or more consecutive days.', 'In all, 420 patients met inclusion criteria: 174 patients exposed to beta-blockers [BB(+)] and 246 not exposed [BB(-)]. Mean age in BB(+) group was 50 years and 36 years in BB(-) group (p < 0.001). Mean Injury Severity Score was 33.6 for BB(+) group and 30.8 for BB(-) group (p = 0.01). Predicted survival (by Trauma and Injury Severity Score) for BB(+) group was 59.1% compared with 70.3% for BB(-) group (p < 0.001). Observed mortality for BB(+) group was 5.1%, 10.8% for BB(-) group (p = 0.036). Adjusted incidence rate ratio of mortality among those exposed to beta-blockers compared with those not exposed was 0.29 (95% confidence interval).']
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['Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants.', 'Given the reported protective actions of bone marrow stromal cells (BMSCs; mesenchymal stem cells) in models of lung and cardiovascular injury, we tested their therapeutic potential in a murine model of BPD.', 'Neonatal mice exposed to hyperoxia (75% O(2)) were injected intravenously on Day 4 with either BMSCs or BMSC-conditioned media (CM) and assessed on Day 14 for lung morphometry, vascular changes associated with pulmonary hypertension, and lung cytokine profile.', 'Injection of BMSCs but not pulmonary artery smooth muscle cells (PASMCs) reduced alveolar loss and lung inflammation, and prevented pulmonary hypertension. Although more donor BMSCs engrafted in hyperoxic lungs compared with normoxic controls, the overall low numbers suggest protective mechanisms other than direct tissue repair. Injection of BMSC-CM had a more pronounced effect than BMSCs, preventing both vessel remodeling and alveolar injury. Treated animals had normal alveolar numbers at Day 14 of hyperoxia and a drastically reduced lung neutrophil and macrophage accumulation compared with PASMC-CM-treated controls. Macrophage stimulating factor 1 and osteopontin, both present at high levels in BMSC-CM, may be involved in this immunomodulation.']
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['Chronic inflammation and oxidative balance are associated with poor diet quality and risk of cancer and other chronic diseases. A diet-inflammation/oxidative balance association may relate to evolutionary discordance.', 'We investigated associations between 2 diet pattern scores, the Paleolithic and the Mediterranean, and circulating concentrations of 2 related biomarkers, high-sensitivity C-reactive protein (hsCRP), an acute inflammatory protein, and F2-isoprostane, a reliable marker of in vivo lipid peroxidation.', 'In a pooled cross-sectional study of 30- to 74-y-old men and women in an elective outpatient colonoscopy population (n = 646), we created diet scores from responses on Willett food-frequency questionnaires and measured plasma hsCRP and F2-isoprostane concentrations by ELISA and gas chromatography-mass spectrometry, respectively. Both diet scores were calculated and categorized into quintiles, and their associations with biomarker concentrations were estimated with the use of general linear models to calculate and compare adjusted geometric means, and via unconditional ordinal logistic regression.', 'There were statistically significant trends for decreasing geometric mean plasma hsCRP and F2-isoprostane concentrations with increasing quintiles of the Paleolithic and Mediterranean diet scores. The multivariable-adjusted ORs comparing those in the highest with those in the lowest quintiles of the Paleolithic and Mediterranean diet scores were 0.61 (95% CI: 0.36, 1.05; P-trend = 0.06) and 0.71 (95% CI: 0.42, 1.20; P-trend = 0.01), respectively, for a higher hsCRP concentration, and 0.51 (95% CI: 0.27, 0.95; P-trend 0.01) and 0.39 (95% CI: 0.21, 0.73; P-trend = 0.01), respectively, for a higher F2-isoprostane concentration.']
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['The anterior impingement test is intended to detect anterosuperior acetabular labral lesions. In patients treated for labral lesions its sensitivity is reportedly 95% to 100%, and in a small group of patients undergoing periacetabular osteotomy, its sensitivity was 59% and specificity 100%. However, the sensitivity, specificity, positive predictive value, and negative predict value of this test to detect these labral lesions in unselected patients with hip pain are unknown.', 'We investigated these four parameters (1) in unselected patients with hip pain, and (2) in three subgroups of patients with dysplasia, femoroacetabular impingement (FAI), and with an intact joint space.', 'We prospectively studied 69 patients (15 men and 54 women) with a mean age of 57.2 years (range, 27-81 years). One observer performed the anterior impingement test in all patients. We determined the presence or absence of an anterosuperior labral lesion with radial MRI in 107 hips (38 patients in both hips: 14 with pain, and 24 without pain). We also investigated the parameters in the three subgroups which consisted of 60 cases of dysplasia, 27 cases of FAI, and 80 cases with intact joint space; the third subgroup partially overlapped the first and second subgroups.', 'The four parameters in all hips were 50.6% (45/89), 88.9% (16/18), 95.7% (45/47), and 26.7% (16/60), respectively. Parameters in the three subgroups were similar to those of all cases.']
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['Hyperthyroidism is the most diagnosed endocrine disorder in cats and radioiodine (131I) is the treatment of choice. The dose emission rate and radioactivity in urine, saliva, and on hair and paws are determined by the dose of administered 131I. A dose reduction of therapeutic 131I could possibly be achieved after recombinant human thyrotropin (rhTSH) administration as in humans with nodular goiter.', 'rhTSH will increase radioiodine uptake in hyperthyroid cats.', 'Five hyperthyroid cats.', 'Twenty-five micrograms rhTSH (day 1) or 2 mL 0.9% sodium chloride (NaCl) (day 9) was injected IV. One hour later, 11.4 +/- 4.1 (mean +/- SD) MBq 123I was injected IV. Radioactive iodine uptake (RAIU) was measured 6, 12, and 24 hours after rhTSH (RAIU-rhTSH) or NaCl (RAIU-blanco) injection. Blood samples for measurement of TT4 were taken before injection of rhTSH or NaCl (TT4(0)) and at the time of imaging.', 'Percentages of RAIU-rhTSH (and RAIU-blanco) at 6, 12, and 24 hours after administration of rhTSH were 34 +/- 18 (31 +/- 21), 46 +/- 20 (38 +/- 18), and 47 +/- 15 (36 +/- 14). There was a statistically significant effect of rhTSH administration on RAIU (P = .043) but not on serum TT4 concentration. Baseline serum TT4(0) concentration influenced RAIU-rhTSH significantly at 6 hours (P = .037).']
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['Patients with longstanding type 1 diabetes may develop microangiopathy due to high cumulative glucose exposure. Also, chronic hyperglycemia is related to cerebral alterations and cognitive dysfunction. Whether the presence of microangiopathy is conditional to the development of hyperglycemia-related cerebral compromise is unclear. Since subcortical, rather than cortical, volume loss was previously related to cognitive dysfunction in other populations, we measured these brain correlates and cognitive functions in patients with longstanding type 1 diabetes with and without microangiopathy.', 'We evaluated differences in subcortical volume and cortical thickness and volume in type 1 diabetic patients with (n = 51) and without (n = 53) proliferative retinopathy and 49 control subjects and related volume differences to cognitive dysfunction. Analyses were corrected for age, sex, systolic blood pressure, and A1C.', 'Putamen and right thalamic volume loss was noted in both patients with and without proliferative retinopathy compared with control subjects (all P < 0.05). Additionally, in patients with proliferative retinopathy relative to control subjects, volume loss of the bilateral nucleus accumbens was found (all P < 0.05). No differences were observed between the two patient groups. Cortical thickness and volume were not different between groups. In pooled analyses, lower left nucleus accumbens volume was associated with cognitive dysfunction (P < 0.035).']
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['Many bedridden patients develop pressure ulcers, not only in hospital but also at home. Clinical studies have indicated cigarette smoking to be a risk factor for pressure ulcers. However, the contribution of nicotine to pressure ulcer formation has not been identified.', 'We aimed to clarify the effect of nicotine on pressure ulcer formation, and its mechanism.', 'Ischaemia-reperfusion (I/R) was performed in rat dorsal skin to induce pressure ulcers. The extent of the resulting necrotic area was determined. To clarify the mechanism of the effect of nicotine, mRNA levels of cyclooxygenase-2 (COX-2), interleukin (IL)-1beta, IL-6 and inducible nitric oxide synthase (iNOS) and protein expression of COX-2 and iNOS in the necrotic area were investigated by real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. Furthermore, the effects of the COX-2 inhibitor NS-398 and the iNOS inhibitor aminoguanidine on necrosis were examined.', 'Skin necrosis in the I/R-treated area was significantly increased by intraperitoneal administration of nicotine (0.175 mg kg(-1) daily). Repeated nicotine administration had little effect on systolic and diastolic blood pressure. I/R treatment increased mRNA levels of COX-2, IL-1beta, IL-6 and iNOS, which were further augmented by nicotine in a dose-dependent manner. Correspondingly, nicotine (0.35 mg kg(-1) daily) markedly enhanced the protein expression of COX-2 and iNOS. Moreover, NS-398 and aminoguanidine showed a tendency to abrogate the increase of I/R-induced skin necrosis caused by nicotine.']
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["Recurrences after surgery for Crohn's disease are frequent and unpredictable. To date, there is little agreement as to which factors increase a patient risk of early recurrence.", 'To assess whether the post-operative behaviour of diseased bowel walls, as determined by ultrasound, may be a useful predictor of relapse.', "A total of 127 Crohn's disease patients were monitored after surgery by means of bowel ultrasound as well as by clinical and laboratory evaluations for a median follow-up of 41.0 months. Bowel wall thickness of diseased loops measured at ultrasound during follow-up was compared with the presurgery values. Multivariable survival analysis was performed to elucidate predictors of early post-operative recurrence. Receiver operating characteristic curves were also constructed taking into account bowel wall thickness for selecting Crohn's disease patients with high risk of clinical/surgical recurrence.", "The estimated 5 years survival probability of symptomatic Crohn's disease recurrence were 90% and 33%, respectively for unchanged/worsened bowel wall thickness vs. improved bowel wall thickness at 12 months from surgery. The hazard ratio for unchanged/worsened bowel wall thickness at 12 months was 8.9 (95% CI: 3.4-23.2). Receiver operating characteristic curve identified a bowel wall thickness > 6.0 mm at 12 months from surgery as directly associated with the risk of having a Crohn's disease recurrence (hazard ratio was 6.5, 95% CI: 2.8-15.4)."]
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['This work was undertaken to determine whether dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia.', 'Marine omega-3 fatty acids improve vascular function, but the underlying mechanism(s) are unclear. We studied the effects of marine omega-3 fatty acids on large artery endothelial function in subjects with hypercholesterolemia.', 'Hypercholesterolemic subjects with no other known cause for endothelial dysfunction were recruited to a prospective, placebo-controlled, randomized, double-blind, parallel-group study. Treatment with omega-3 fatty acids at a dose of 4 g/day (n = 15/group) was compared with placebo, at the beginning (day 0) and end (day 120) of a four-month treatment period. Endothelial function was assessed pre- and posttreatment by noninvasive ultrasonic vessel wall tracking of brachial artery flow-mediated dilation (FMD).', 'Treatment with marine omega-3 fatty acids resulted in a significant improvement in FMD (0.05 +/- 0.12 to 0.12 +/- 0.07 mm, p < 0.05) and a significant reduction in triglycerides (2.07 +/- 1.13 to 1.73 +/- 0.95 mmol/liter, p < 0.05), whereas treatment with placebo resulted in no change in FMD (0.03 +/- 0.10 to 0.04 +/- 0.10 mm) or triglycerides (2.29 +/- 2.09 to 2.05 +/- 1.36 mmol/liter) (both p < 0.05 treated compared with control). Responses to sublingual glyceryl trinitrate were unchanged.']
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['Atherosclerosis is an immunoinflammatory disease. Here we examined the role of leukocyte-derived interleukin 10 (IL-10) on advanced atherosclerosis development in low-density lipoprotein receptor knockout (LDLr-/-) mice.', 'Bone marrow cells harvested from C57BL/6 IL-10-/- and IL-10+/+ mice were transplanted into irradiated male LDLr-/- mice. Four weeks after transplantation, mice were fed a high-fat cholate-free diet for 14 weeks. Despite no differences in weights, serum total, and HDL-cholesterol levels between the 2 groups, IL-10 deficiency in leukocytes induced a >2-fold increase in lesion development in the thoracic aorta compared with controls. We also found a significant 35% increase in aortic root lesion area of IL-10-/- mice compared with IL-10+/+ mice. Furthermore, IL-10 deficiency led to a marked increase in lymphocyte and macrophage accumulation associated with a significant reduction in collagen accumulation. Finally, transfer of IL-10-/- splenocytes to LDLr-/- mice resulted in a 3-fold increase in lesion size in the aortic sinus compared with mice transplanted with IL-10+/+ splenocytes.']
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['The incidence and mortality associated with intrahepatic cholangiocarcinoma is increasing in many countries and documentation of disease outcome is sparse. The present study was undertaken to investigate the prognostic factors for intrahepatic cholangiocarcinoma (ICC) following surgical resection. The impact of pre-existing HBV virus infection and adjuvant chemotherapy on the overall survival was also evaluated.', 'Clinical and pathological data were collected retrospectively from 81 patients undergoing surgery for ICC between 2005 and 2011, at The Henan Province Tumor Hospital and the First Affiliated Hospital of Zheng Zhou University. Survival and prognosis were analyzed using the Kaplan-Meier method and COX regression model.', 'The population included 37 patients who were HBsAg\u2009+\u2009or anti-HBc+, 21 patients who were anti-HBs\u2009+\u2009positive and 18 patients who received adjuvant chemotherapy. The overall 1- and 3-year survival rates were 51% and 20%, respectively. The median survival was 12.2\xa0months. Univariate analysis identified the following prognostic factors: HBV virus infection or HBV vaccine prior to resection (P\u2009=\u20090.017); adjuvant chemotherapy (P\u2009=\u20090.001); preoperative serum CA19-9 (>\u2009200\u2009U/mL; P\u2009=\u20090.015); GGT (>\u200964\u2009U/L; P\u2009=\u20090.008), ALP (>\u2009119\u2009U/L; P\u2009=\u20090.01); lymph node metastasis (P\u2009=\u20090.005); radical resection (P\u2009=\u20090.021); intrahepatic metastasis (P\u2009=\u20090.015) and diabetes (P\u2009=\u20090.07). Multivariate analysis identified chronic HBV infection (RR\u2009=\u20090.583; P\u2009=\u20090.041), anti-HBs positivity (RR\u2009=\u20090.680; P\u2009=\u20090.050), adjuvant chemotherapy (RR\u2009=\u20090.227; P\u2009<\u20090.001), lymph node metastasis (RR\u2009=\u20092.320; P\u2009=\u20090.001), and intrahepatic duct stones (RR\u2009=\u20090.473; P\u2009=\u20090.032) as independent prognostic factors.']
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['Rotational atherectomy (RA) has traditionally been carried out using 7 or 8\u2009Fr guides through a transfemoral approach to allow for passage of 2.0\u2009mm burrs or larger. With transradial percutaneous coronary intervention becoming more common, our aim was to investigate whether transradial RA would offer equivalent rates of procedural success when compared with transfemoral RA.', 'Using a prospective percutaneous coronary intervention registry, we identified all patients who had undergone RA at the University Health Network between January 2001 and December 2012 and compared those in whom the transfemoral approach had been used with those in whom the transradial approach had been used.', 'A total of 119 patients were analyzed (67 femoral, 52 radial). Larger guides were used in the femoral group compared with the radial group (6.79 vs. 6.31\u2009Fr, P<0.001), but there was no significant difference in the number of burrs used or the average size of the burrs. There was no significant difference in the procedural success rate (91 vs. 96%, P=0.46), fluoroscopy time (40.5 vs. 43.8\u2009min, P=0.37), radiation dose (27743 vs. 29939\u2009cGy\u2009cm, P=0.50), or contrast use (429 vs. 384\u2009ml, P=0.19) between the two groups. Patients in the femoral group were more likely to have a transvenous pacing wire inserted (25 vs. 6%, P=0.006). Access site crossover tended to occur more frequently in the radial group (6 vs. 0%, P=0.08).']
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['Cardiac surgery using cardiopulmonary bypass (CPB) is performed widely, given the progress in cardioprotective methods. However, endotoxemia caused by CPB leads to systemic inflammatory response syndrome and deterioration of organ function. We evaluated the effectiveness of endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge (PMX) in CPB.', 'Pigs weighing about 25 kg were divided into control (n = 5) and PMX (n = 5) groups. Normothermic CPB was performed in the control group, while endotoxin was removed with PMX under normothermic CPB in the PMX group. Endotoxin removal was performed from the start to end of CPB. The end-systolic pressure-volume ratio (E(max)), left ventricular pressure (LVP), maximum and minimum rates of increase in LVP (+/-LVdp/dt), and cardiac output (CO) were measured 2 h after CPB, and the recovery rates of the parameters were compared between the two groups. A histopathological study was also conducted.', 'The recovery rates of E(max), CO, and LVP were significantly better (P < 0.05) in the PMX group than in the control group. The PaO(2) 2 h after CPB was significantly higher (P < 0.05) in the PMX group than in the control group. The interleukin (IL)-8 level 2 h after CPB was significantly lower (P < 0.05) in the PMX group. Histopathologically, the heart and pulmonary tissues were better preserved in the PMX group.']
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