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['Recent studies highlight a potential role of cholesterol metabolic disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within proximity of linkage peaks on chromosome 9q influence AD and plays a key role in cellular cholesterol efflux in the brain.', 'We studied the role of R219K and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients and 349 comparisons of Chinese Han. Genotyping of R219K and V825I were performed by PCR-restriction fragment length polymorphism analysis.', 'The genotype distribution of R219K was different with more RK in total AD group (χ(2) = 8.705, df = 2, p = 0.013), late-onset AD (LOAD) group (χ(2) = 10.636, df = 2, p = 0.005), APOE non-ε4ε4 group (χ(2) = 9.900, df = 2, p = 0.007), and female AD group (χ(2) = 8.369, df = 2, p = 0.015). Logistic regression manifested the risk of AD increased in RK carriers in total AD group (Wald = 6.102, df = 1, p = 0.014, odds ratio [OR]: 1.546, 95% confidence interval [95% CI]: 1.094-2.185), LOAD group (Wald = 7.746, df = 1, p = 0.005, OR: 1.921, 95% CI: 1.213-3.041), and APOE non-ε4ε4 group (Wald = 6.399, df = 1, p = 0.011, OR: 1.586, 95% CI: 1.109-2.266). K allele (RK + KK) also increased the risk of AD compared with RR allele in LOAD group (Wald = 4.750, df = 1, p = 0.029, OR: 1.619, 95% CI: 1.050-2.497). However, no discrepancy was found in V825I. In R219K, age at onset (AAO) was significantly lower by 4.9 years on average in patients of KK genotype than those of RK in APOE ε4 carrying group and higher by 5.5 years in patients of KK genotype than those of RR in APOE ε4 noncarrying group. In V825I, AAO was diseased by 4.3 years in II genotype compared with VV genotype in APOE ε4 noncarrying group and 3.4 years in APOE ε4ε4 noncarrying group.']
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['Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding.', 'Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011.', 'Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding.']
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['Acute rejection (AR) remains a challenge in organ transplantation. Preconditioning donor organs can reduce AR and prolong survival. Whether preconditioning with cromolyn (CRM), a mast cell (MC) stabilizer, or compound 48/80 (CMP 48/80), a MC degranulator, can alleviate AR and prolong survival has not been studied.', 'We used the male-DA-to-female-Lewis-rat orthotopic liver transplantation (OLT) model. Donors were preconditioned with CRM in a MC stabilizing way (CRM group) or CMP 48/80 in a MC depleting way (CMP 48/80 group). Rats preconditioned with phosphate-buffered saline were used as controls (PBS group). After preconditioning, OLT surgeries were carried out. OLT male-Lewis-to-female-Lewis-rats were used as the syngeneic group (syngeneic group).', 'Rats in the PBS group developed AR rapidly and died at 7.40 ± 1.14 days. Rats in the CRM and CMP 48/80 groups had significantly slower rejections and died at day 17.40 ± 1.67 or 14.20 ± 2.28, respectively (P < .05). Rats in the syngeneic group survived more than 60 days. Rejection activity indexes (RAIs) and liver functions were all alleviated through CRM or CMP 48/80 preconditioning. Interferon-γ messenger RNA (mRNA) expressions were reduced and interleukin-10 mRNA levels were higher in allografts in the CRM and CMP 48/80 groups, compared with the PBS group. These were confirmed by testing serum interferon-γ and interlerkin-10.']
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['Advances in dairy technology make it possible to enrich infant formula with specific bovine milk components that may enhance nutrient status. Glycomacropeptide, a carbohydrate-rich casein peptide, may increase absorption of calcium, iron, or zinc. alpha-Lactalbumin, a major breast-milk protein, may contribute to a balanced amino acid pattern and increase calcium and zinc absorption.', 'We determined the effects of glycomacropeptide- and alpha-lactalbumin-supplemented infant formula on growth; trace mineral status; iron, zinc, and calcium absorption; and plasma amino acid, blood urea nitrogen, and plasma insulin concentrations.', 'Infant rhesus monkeys (n = 5 infants per group) were breastfed or fed control or alpha-lactalbumin- or glycomacropeptide-supplemented formula from birth to 4 mo of age. Hematologic measures and growth were assessed monthly. Mineral absorption was measured with radioisotopes and whole body counting.', 'Infants fed glycomacropeptide had higher food intake than did other formula-fed infants. Infants fed glycomacropeptide or control formula had higher hematocrit values than did infants that were breastfed or fed alpha-lactalbumin. Infants fed glycomacropeptide or control formula had higher plasma zinc and zinc absorption than did breastfed infants. Where differences were observed, breastfed infants and infants fed alpha-lactalbumin had similar plasma essential amino acid and insulin profiles, which were different from those of infants fed glycomacropeptide or control formula.']
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['Hyperhomocysteinemia has been linked to cardiovascular morbidity and mortality by numerous authors. Whether this association is causal or not remains uncertain. The aim of the study was to investigate the association of hyperhomocysteinemia with the degree of carotid atherosclerosis in stroke patients.', 'We studied 97 Greek patients in our stroke unit who were hospitalized as a result of ischemic stroke between March 2006 and May 2007. The patients were divided into two groups: the first (52 patients) included stroke patients with serum levels of homocysteine below 15 mumol/L, but in the second group (45 patients) serum homocysteine exceeded this value. We measured carotid intima-media thickness (cIMT) in all patients and correlated it with serum homocysteine.', 'The mean homocysteine concentration was 11.5 mumol/L in the first group and 21.5 mumol/L in the second group. Carotid IMT was 1.012 mm in the first group, and 1.015 mm in the second group, an insignificant difference. On the contrary, serum folate concentration was 21.3 nmol/L in the first group compared with 16.7 nmol/L in the second group (p < 0.001). VitB12 was 401 pmol/L in the first group and 340 pmol/L in the second group, a statistically significant difference (p < 0.001).']
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['Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood-brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown.', 'We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO.', 'The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients.', 'NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF/serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions.']
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['Retinoids are important for growth plate chondrocyte maturation, but their downstream effectors remain unclear. Recently, CTGF (CCN2) was found to regulate chondrocyte function, particularly in the hypertrophic zone. The goal of the study was to determine whether CTGF is a retinoid signaling effector molecule, how it is regulated, and how it acts.', 'Using a combination of in vivo and in vitro approaches, we carried out a series of studies at the cellular, biochemical, and molecular level to determine whether and how retinoid signaling is related to expression and function of connective tissue growth factor (CTGF) in chondrocyte maturation and endochondral ossification.', 'Limbs of chick embryos in ovo were implanted with retinoic pan-antagonist RO 41-5253-filled beads, and phenotypic changes were assessed by in situ hybridization. CTGF gene expression and roles were tested in primary cultures of immature and hypertrophic chondrocytes. Cross-talk between retinoid signaling and other pathways was tested by determining endogenous levels of active ERK1/2 and p38 MAP kinases and phenotypic modulations exerted by specific antagonists of mitogen-activated protein (MAP) kinases and BMP signaling (Noggin).', 'Interference with retinoid signaling blocked expression of CTGF and other posthypertrophic markers in long bone anlagen in vivo and hypertrophic chondrocyte cultures, whereas all-trans-retinoic acid (RA) boosted CTGF expression and even induced it in immature proliferating cultures. Exogenous recombinant CTGF stimulated chondrocyte maturation, but failed to do so in presence of retinoid antagonists. Immunoblots showed that hypertrophic chondrocytes contained sizable levels of phosphorylated ERK1/2 and p38 MAP kinases that were dose- and time-dependently increased by RA treatment. Experimental ERK1/2 inhibition led to a severe drop in baseline and RA-stimulated CTGF expression, whereas p38 inhibition increased it markedly. These responses were gene-specific, because the opposite was seen with other hypertrophic chondrocyte genes such as collagen X and RA receptor gamma (RARgamma). Tests with Noggin showed that RA induction of CTGF expression was negatively influenced by BMP signaling, whereas induction of collagen X expression was BMP-dependent.']
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['The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors.', 'Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets.', 'We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet.']
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['Circadian rhythms are known to influence a variety of biological phenomena such as cell cycle, sleep-wake rhythm, hormone release and other important physiological functions. Given that cell cycle entry of hibernating hematopoietic stem cells (HSCs) plays a critical role in controlling hematopoiesis, we asked functional significance of the clock gene Bmal1, which plays a central role in regulating circadian rhythms as a transcription factor. Here we investigated the necessity of Bmal1 for HSC functions using Bmal1 deficient (Bmal1⁻/⁻) mice.', 'Using colony-forming assays in vitro, we found that the frequency of mixed colony formation between Bmal1⁺/⁺ and Bmal1⁻/⁻ CD34-KSL cells does not differ significantly. Competitive bone marrow assays also revealed that Bmal1⁻/⁻ bone marrow cells competed normally with wild-type cells and displayed long-term multi-hematopoietic lineage reconstitution. In addition, there were no significant differences in the frequencies and hibernation state of bone marrow HSCs between Bmal1⁺/⁺ and Bmal1⁻/⁻ mice, suggesting that they are independent of circadian rhythms.']
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['Anemia is common in IBD patients and intravenous iron treatment is preferred. The drug cost of intravenous iron carboxymaltose is approximately twice the cost of intravenous iron sucrose. The aim was to evaluate the health care costs of intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject®, Vifor) treatment to IBD patients in an outpatient setting.', 'Based on data from 111 IBD patients treated with intravenous iron in an outpatient setting health care costs were evaluated by means of Budget Impact Analysis, Cost Effective Analysis and Cost Benefit Analysis.', "The Cost Effective Analysis showed that iron carboxymaltose was more cost-effective than iron sucrose, due to fewer outpatient setting visits. Even a sensitivity analysis using a reduced patient income (50%) in the Cost Effective Analysis showed iron carboxymaltose to be the most cost effective treatment. The Budget Impact Analysis from a hospital perspective showed that iron carboxymaltose was more expensive than iron sucrose regardless of the dose given. In contrast the Cost Benefit Analysis showed that the average patients' 'willingness to pay' for a total of iron dose of 1400 mg was €233 in order to reduce the number of infusions from 7 to 2 by using iron carboxymaltose rather than iron sucrose."]
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['Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG level on cardiovascular events has not been fully investigated.', 'We enrolled 240 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1\xa0year. We excluded patients with a history of acute coronary syndrome, advanced chronic kidney disease (estimated glomerular filtration rate\xa0<30\xa0mL/min/1.73\xa0m', 'Subjects were divided into two groups according to clinical outcomes: the Event (+) group (n\xa0=\xa040) and the Event (-) group (n\xa0=\xa0200). No significant differences were observed, except for the number of diseased vessels and the prevalence of statin use, in baseline clinical characteristics between the two groups. Serum levels of 1,5-AG at follow-up were significantly lower in the Event (+) group than in the Event (-) group (P\xa0=\xa00.02). A significant reduction in 1,5-AG level from baseline to follow-up was observed in the Event (+) group compared with the Event (-) group (P\xa0=\xa00.04). The association between 1,5-AG levels at follow-up and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P\xa0=\xa00.04).']
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['Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes.', 'C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.', 'Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.']
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['The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage.', 'Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions.', 'Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism.']
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['Approximately two-thirds of the patients with newly diagnosed partial epilepsy remained on their first antiepileptic drug (AED) for 2 years in clinical practice. We aimed to analyze retention on the first AED for 2 years in newly diagnosed cryptogenic partial epilepsy patients in clinical practice and whether the presence of epileptiform discharges on the initial EEG was a predictor of the failure of retention on the first AED.', 'For the purpose of this study, we retrospectively reviewed epilepsy database. On the Epilepsy Database, we found 495 newly diagnosed epilepsy patients who had been followed up for at least 2 years. Of these 495 newly diagnosed epilepsy patients, 172 patients had cryptogenic partial epilepsy. The outcome of this study was the retention rate for the first AED for 2 years. In addition, we analyzed the retention on first AED according to the presence or absence of epileptiform discharges on the initial EEG using Kaplan-Meier survival analysis.', 'Overall, retention rate on the first AED for 2 years was 51%. The main lesion of retention failure was a lack of tolerance. The presence of epileptiform discharges on the initial EEGs was significantly related to the failure of retention on the first AED (p=0.003).']
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['Reduced intrahepatic perfusion that occurs during contrast angiography performed after administration of halothane anesthesia is thought to result from halothane-induced systemic hemodynamic alterations, such as reduced splanchnic blood flow, rather than intrahepatic microvascular alterations. The authors postulate that intrinsic hepatic effects caused by inhalational anesthetic agents rather than contrast materials, further reduce liver perfusion.', 'With use of dynamic video microscopy, intrahepatic microvascular flow rates and patterns, hepatic cord/sinusoidal diameters, portal venous pressure changes, and quantitative and qualitative Kupffer cell phagocytic activity were continuously recorded in isolated perfused rat livers before and during exposure to 1.5% halothane in O2/CO2, with and without the addition of iothalamate meglumine.', 'Exposure of livers to halothane resulted in intrahepatic portovenous shunting secondary to obstruction to sinusoidal outflow, diminished sinusoidal perfusion, and a mean elevation in terminal portal venous pressure of 12.8 mm Hg. Kupffer cell phagocytic activity was reduced even when normalized for flow within sinusoids. None of these changes were attributed to use of contrast material.']
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['Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action.', 'The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600\xa0beats·min(-1) for 1\xa0week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2\xa0weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed.', 'The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF.']
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['The role of cortical drive in stroke recovery for the lower extremity remains ambiguous. The purpose of this study was to investigate the relationship between cortical drive and gait speed in a group of stroke survivors.', 'Eighteen individuals with stroke were dichotomized into fast or slow walking groups. Transcranial magnetic stimulation (TMS) was used to collect motor evoked potentials (MEPs) from the tibialis anterior of each lower extremity during rest, paretic muscle contractions, and nonparetic muscle contractions. An asymmetry-index (AI) was calculated using motor thresholds and compared between groups. The average MEP of the paretic leg during TMS at maximal intensity (MEP100) for each condition was compared within and between groups.', 'A significant positive correlation was found between AI and walking speed. Slow-walkers had greater MEP100s during the nonparetic contraction than during the paretic contraction or rest conditions. In contrast, fast-walkers had greatest MEP100s during the paretic contraction.']
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['Cerebral autoregulation is important to maintain a constant perfusion in the face of changes in blood pressure. It is reported to be impaired in pathologic states, including hypertension, cerebral infarction, and head injury. However, it is not clear whether cerebral autoregulation is impaired in resuscitated patients after cardiac arrest.', 'Cerebral autoregulation in comatose patients after cardiac arrest was assessed by using an indirect method of cerebral blood flow (CBF). Eight patients who had cardiac arrest outside of the hospital and were successfully resuscitated in the emergency room were included in this study. A catheter was inserted percutaneously into the right internal jugular vein and positioned so that the tip was in the jugular bulb. Mean arterial pressure (MAP) was changed to a value of 30% lower or higher than baseline MAP by infusing trimethaphan or methoxamine, respectively. At each MAP level, arterial and jugular bulb venous blood gases were measured, and arterial-jugular bulb venous oxygen content difference (AVDO2) was calculated.', 'The 1/AVDO2 (CBFI) and oxygen saturation of jugular bulb venous blood (SjvO2) significantly decreased at the lower MAP level, and significantly increased at the higher MAP level. The ratio of the CBFI at the lower MAP level to the CBFI at baseline (CBFI-L/CBFI-B) inversely correlated with the SjvO2 at baseline.']
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['The cytokine profile plays an important role in treatment outcome of hepatitis C virus (HCV) infection, and probably modulates the immune response against HCV. The aim of this study was to evaluate which cytokines affect the response to interferon-α (IFN-α) and ribavirin therapy and how these cytokines change 72 weeks after starting anti-HCV therapy in HIV/HCV-coinfected patients.', 'We carried out a retrospective follow-up study of 65 patients on anti-HCV therapy. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Cytokines were measured using a multiplex immunoassay kit.', 'On starting anti-HCV therapy, non-responder (NR) patients had higher levels of interleukin (IL)-6, IL-9, IL-10 and tumour necrosis factor (TNF)-α (P < 0.05), while IL-17A levels were increased in SVR patients (P = 0.058). However, only patients with high levels of IL-6 and IL-9 had decreased odds to achieve SVR (P < 0.05). Plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure [area under the ROC curve (AUC) 0.839 (95% CI 0.733-0.945) and AUC 0.769 (95% CI 0.653-0.884)]. In addition, during anti-HCV therapy, IL-1β showed an increase in NR patients (P = 0.015) and IL-10 decreased in SVR patients (P = 0.049). After clearing HCV infection, low levels of TNF-α, IL-6, IL-9, IL-10, IL-13 and IL-22 were found in SVR patients (P < 0.05), as well as IL-1β, but only near statistical significance (P = 0.073).']
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['Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4\u2005years.', 'In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4\u2005years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ', 'Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4\u2005years.']
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['Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy than ductal carcinoma. In molecular terms, MBCs usually cluster with triple-negative breast cancers (TNBCs), but have a worse prognosis than TNBCs. Studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches. The aim of the present study was to characterise MBCs on a molecular level and test programmed death-ligand 1 (PD-L1) biomarker expression in MBCs for future therapeutic interventions.', 'We profiled 297 samples (MBC (n=75), TNBC (n=106), human epidermal growth factor receptor 2 (HER2)-positive breast cancers (n=32) and hormone-positive breast cancers (n=84)) by next-generation sequencing. Immunohistochemistry for PD-L1 and programmed cell death 1 (PD-1) expression was performed using automated procedures.', 'The most commonly mutated genes in MBCs included TP53 (56%) and PIK3CA (23%). Pathogenic mutations in other genes, including HRAS, FBXW7, PTEN, AKT1 and SMAD4, were rare. PD-L1 expression was detected in a significantly higher proportion of MBCs (46%) than in other subtypes (6% each in hormone-positive and HER2-positive breast cancers, and 9% in TNBC, not otherwise specified, p<0.001). PD-1-positive tumour infiltrating lymphocytes (TILs) varied greatly in MBCs.']
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['Laparoscopic procedures are associated with several complications, such as hemodynamic, respiratory, and endocrine complications. In our previous clinical study, plasma epinephrine and norepinephrine concentrations remained unchanged after the insertion of a Veress needle, but increased significantly immediately after insufflation with carbon dioxide into the peritoneum. The mechanisms for this increase are unknown.', 'To investigate whether gas insufflation during pneumoperitoneum affects plasma catecholamine concentrations during laparoscopic procedures.', 'Experimental study in pigs.', 'The plasma concentrations of epinephrine and norepinephrine were measured in the pigs before and after pneumoperitoneum. The mean arterial pressure, heart rate, cardiac output, and arterial blood gas levels were measured, and the systemic vascular resistance was calculated.', 'Air, nitrous oxide, or carbon dioxide were insufflated in turn into the peritoneal cavity of supine pigs. Thereafter, carbon dioxide was insufflated into the peritoneal cavity while the pig was in the left lateral decubitus position, and then in the right lateral decubitus position. Measures were performed before pneumoperitoneum and at the intra-abdominal pressures of 10 mm Hg and 20 mm Hg. One hour of resting time was allowed between each procedure.', 'As compared with baseline values, the plasma concentrations of epinephrine and norepinephrine remained unchanged at 10 mm Hg but increased significantly at 20 mm Hg regardless of the gas used for the pneumoperitoneum (P<.05). The type of gas and differences in the position of the animals had no effect on the plasma epinephrine and norepinephrine concentrations.']
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['To determine the effects of food viscosity on the ability of rats to compensate for calories in a dietary supplement.', 'In a series of four experiments, rats consumed dietary supplements equated for caloric and nutritive content but differing in viscosity. Experiments 1 to 3 examined the ability of the rats to compensate for the calories consumed in low- compared with high-viscosity premeals by reducing intake of a subsequent test meal. Caloric compensation was assessed with a wide range of premeal viscosity levels and with two different non-nutritive thickening agents. Experiment 4 assessed the effects of consuming daily a low-viscosity compared with an equicaloric high-viscosity dietary supplement on longer term body weight gain.', 'Consuming a lower viscosity premeal was followed by significantly more caloric intake (i.e., less caloric compensation) compared with consuming premeals with higher viscosity levels. This effect was not specific to one thickening agent. Furthermore, rats given a low-viscosity supplement daily gained significantly more weight over a 10-week period compared with rats given a high-viscosity supplement.']
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['Inflammatory responses play a pivotal role in the pathogenesis of hypertensive cardiac remodeling. Macrophage recruitment and polarization contribute to the development of cardiac fibrosis. Although serum-glucocorticoid regulated kinase 1 (SGK1) is a key mediator of fibrosis, its role in regulating macrophage function leading to cardiac fibrosis has not been investigated. We aimed to determine the mechanism by which SGK1 regulates the cardiac inflammatory process, thus contributing to hypertensive cardiac fibrosis.', 'After angiotensin II infusion in mice, cardiac hypertrophy and fibrosis developed in wild-type but not SGK1 knockout mice, with equal levels of hypertension in both groups. Compared with wild-type hearts, SGK1 knockout hearts showed less infiltration of leukocytes and macrophages. Importantly, SGK1 deficiency led to decreased proportion of alternatively activated (M2) macrophages and increased levels of profibrotic cytokines. Angiotensin II infusion induced phosphorylation and nuclear localization of signal transducer and activator of transcription 3 (STAT3) whereas SGK1 knockout hearts showed this effect attenuated. In a 3-dimensional peptide gel culture, inhibition of STAT3 suppressed differentiation into M2 macrophages. Coculture of macrophages with cardiac fibroblasts in 3-dimensional peptide gel stimulated the expression of α-smooth muscle actin and collagen in cardiac fibroblasts. However, SGK1 knockout mice with macrophage deficiency showed reduced fibroblast-to-myofibroblast transition.']
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['Defining the molecular target for strontium in osteoblasts is important for understanding the anabolic effects of this cation on bone. The current studies demonstrate that a G-protein-mediated response to strontium persists in osteoblasts that lack CASR, suggesting a predominant role for a novel cation-sensing receptor in mediating the osseous response to strontium.', 'Strontium has anabolic effects on bone and is currently being developed for the treatment of osteoporosis. The molecular target for strontium in osteoblasts has not been determined, but the existence of CASR, a G-protein-coupled receptor calcium-sensing receptor, raises the possibility that strontium actions on bone are mediated through this or a related receptor.', 'We used activation of a transfected serum response element (SRE)-luciferase reporter in HEK-293 cells to determine if CASR is activated by strontium. In addition, we examined strontium-mediated responses in MC3T3-E1 osteoblasts and osteoblasts derived from wild-type and CASR null mice to determine if other cation-sensing mechanisms are present in osteoblasts.']
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['Because burn victims are at risk of having bone loss, a cross-sectional study was undertaken to determine whether severe burn injury had acute and long-term effects on bone mass or on the incidence of fractures in children.', 'Dual-energy x-ray absorptiometry of the lumbar portion of the spine was performed on 68 children: 16 moderately burned (15% to 36% of total body surface area) and 52 age-matched severely burned (> or = 40% of total body surface area). Twenty-two severely burned children were hospitalized and studied within 8 weeks of their burn, and 30 others were studied approximately 5 years after discharge. In the severely burned group, both hospitalized and discharged, serum and urine were analyzed for calcium, phosphorus, intact parathyroid hormone, osteocalcin, and type I collagen telopeptide.', 'Sixty percent of severely burned patients had age-related z scores for bone density less than -1, and 27% of severely burned patients had age-related z scores for bone density less than -2 (p < 0.005, for each). In the moderately burned group, 31% of patients had z scores less than -1 (p < 0.005 vs normal distribution), but only 6% had z scores less than -2 (p value not significant). There was evidence of increased incidence of fractures after discharge in the severely burned patients. Biochemical studies were compatible with a reduction in bone formation and an increase in resorption initially, and with a long-term persistence of low formation.']
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['We previously reported that human tumor-derived endothelial cells (TEC) have an angiogenic phenotype related to the autocrine production of several angiogenic factors. The purpose of the present study was to evaluate whether an enhanced synthesis of platelet-activating factor (PAF) might contribute to the proangiogenic characteristics of TEC and whether its inactivation might inhibit angiogenesis.', 'To address the potential role of PAF in the proangiogenic characteristics of TEC, we engineered TEC to stably overexpress human plasma PAF-acetylhydrolase (PAF-AH), the major PAF-inactivating enzyme, and we evaluated in vitro and in vivo angiogenesis.', 'TECs were able to synthesize a significantly enhanced amount of PAF compared with normal human microvascular endothelial cells when stimulated with thrombin, vascular endothelial growth factor, or soluble CD154. Transfection of TEC with PAF-AH (TEC-PAF-AH) significantly inhibited apoptosis resistance and spontaneous motility of TEC. In addition, PAF and vascular endothelial growth factor stimulation enhanced the motility and adhesion of TEC but not of TEC-PAF-AH. In vitro, TEC-PAF-AH lost the characteristic ability of TEC to form vessel-like structures when plated on Matrigel. Finally, when cells were injected s.c. within Matrigel in severe combined immunodeficiency mice or coimplanted with a renal carcinoma cell line, the overexpression of PAF-AH induced a significant reduction of functional vessel formation.']
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["We examined the mechanism by which PTHrP and PTH inhibit KS483 osteoblastic differentiation. We show that PTHrP and PTH inhibit differentiation downstream of early BMP signaling and downregulated components of the hedgehog (Hh) signaling cascade. In addition, PTHrP and PTH repressed RunX2 and osx expression. Overexpression of either gene, however, could not relieve PTHrP and PTH's inhibitory actions. Our data suggest that multiple parallel mechanisms are involved in the inhibition of osteoblast differentiation and matrix mineralization by PTHrP and PTH.", 'PTH-related peptide (PTHrP) and PTH are potent inhibitors of osteoblast differentiation in vitro by as yet unexplained mechanisms.', 'We treated murine bone marrow stromal cells and the mesenchymal progenitor cell line KS483 with PTHrP and PTH in combination with either BMPs or hedgehog (Hh) and measured early and late markers of osteoblast differentiation and studied the expression of RunX2 and Osterix (osx). In addition, we examined the PTHrP and PTH response in stable KS483 cells overexpressing either RunX2 or osx.', 'PTHrP and PTH inhibited BMP- and Hh-induced osteogenesis downstream of early BMP signaling and by downregulation of components of the Hh signaling cascade. PTHrP and PTH prevented the upregulation of RunX2 expression associated with osteoblast differentiation in an indirect response. However, PTHrP and PTH could still inhibit differentiation, and particularly matrix mineralization, of cells expressing RunX2. In addition, PTHrP and PTH potently downregulated osx expression only in mature osteoblasts in an intermediate early response, but osx overexpression could not relieve the inhibitory effects of PTHrP and PTH on matrix mineralization.']
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['Cancer stem cells represent an attractive therapeutic target for tumor eradication. The present study aimed to determine whether CD133 expression may identify cells with characteristics of cancer stem/progenitor cells in human endometrial tumors.', 'We analyzed 113 tumor samples for CD133/1 expression by flow cytometry, immunohistochemistry, and semiquantitative reverse transcription-PCR. CD133(+) cells were isolated and used to assess phenotypic characteristics, self-renewal capacity, ability to maintain CD133 expression and form sphere-like structures in long-term cultures, sensitivity to chemotherapeutic agents, gene expression profile, and ability to initiate tumors in NOD/SCID mice.', 'Primary tumor samples exhibited a variable degree of immunoreactivity for CD133/1, ranging from 1.3% to 62.6%, but stained negatively for other endothelial and stem cell-associated markers. Isolated CD133(+) cells expanded up to 4.6-fold in serum-replenished cultures and coexpressed the GalNAcalpha1-O-Ser/Thr MUC-1 glycoform, a well-characterized tumor-associated antigen. Dissociated bulk tumors formed sphere-like structures; cells grown as tumor spheres maintained CD133 expression and could be propagated for up to 12 weeks. CD133(+) cells purified from endometrioid adenocarcinomas were resistant to cisplatin-induced and paclitaxel-induced cytotoxicity and expressed a peculiar gene signature consisting of high levels of matrix metalloproteases, interleukin-8, CD44, and CXCR4. When serially transplanted into NOD/SCID mice, CD133(+) cells were capable of initiating tumor formation and recapitulating the phenotype of the original tumor.']
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['The tumor suppressor menin (MEN1) is mutated in the inherited disease multiple endocrine neoplasia type I, and has several documented cellular roles, including the activation and repression of transcription effected by several transcription factors. As an activator, MEN1 is a component of the Set1-like mixed lineage leukemia (MLL) MLL1/MLL2 methyltransferase complex that methylates histone H3 lysine 4 (H3K4). MEN1 is localized to the signal transducer and activator of transcription 1 (STAT1)-dependent gene, interferon regulatory factor 1 (IRF1), and is further recruited when IRF1 transcription is triggered by interferon-γ signaling.', 'RNAi-mediated knockdown of MEN1 alters the H3K4 dimethylation and H3 acetylation profiles, and the localization of histone deacetylase 3, at IRF1. While MEN1 knockdown does not impact the rate of transcription, IRF1 heteronuclear transcripts become enriched in MEN1-depleted cells. The processed mRNA and translated protein product are concomitantly reduced, and the antiviral state is attenuated. Additionally, the transcription start site at the IRF1 promoter is disrupted in the MEN1-depleted cells. The H3K4 demethylase, lysine specific demethylase 1, is also associated with IRF1, and its inhibition alters H3K4 methylation and disrupts the transcription start site as well.']
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['Axillary dissection is frequently performed during the treatment of operable breast cancer, and is associated with certain morbidities. Accumulation of axillary fluid, otherwise known as a seroma, is a frequent complication that appears to be related to the degree of dissection. Based on empirical evidence, surgeons have attempted to reduce the occurrence and duration of seromas by using suction drainage, but this concept has been challenged by several authors.', 'To determine if the natural history of seroma fluid accumulation after axillary surgery is altered by the duration of suction drainage or non-placement of a drain.', 'Ninety consecutive patients having axillary dissection for breast cancer had either prolonged suction drainage (mean 9.6 days), short duration drainage (2 days), or had no drain placed. Seromas were aspirated and the time to cessation of fluid accumulation determined, as well as any other wound complications.', 'There was no difference in the number of wound complications or the duration of fluid accumulation between the three groups, being 26.6, 25.7, and 27.9 days, respectively. Patients having no drains placed required more frequent aspirations.']
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['High-altitude pulmonary edema (HAPE), which develops on exertion under hypoxic conditions, aggravates due to endothelial dysfunction. Repeat events of the disorder suggests of genetic susceptibility. Endothelial nitric oxide synthase gene (NOS3), a regulator of vasodilation, has emerged as a strong candidate marker. In the present study, we investigated G894T, 27-base-pair 4b/4a (variable number of tandem repeat), -922A/G, and -786T/C polymorphisms of NOS3, individually or in combination, for an association with HAPE.', 'A cross-sectional case control study.', 'Blood samples of HAPE-resistant lowlanders (HAPE-r) were obtained at sea level, and blood samples of patients with HAPE (HAPE-p) were obtained at Sonam Norboo Memorial Hospital, Leh, at 3,500 m.', 'The study groups consisted of 60 HAPE-r inducted two to three times to altitudes > 3,600 m; and 72 HAPE-p, who had HAPE on their first visit to high altitude.', 'Nitrogen oxides (NOx) at 77.9 +/- 28.6 micromol/L were significantly elevated in HAPE-r as compared to 42.39 +/- 12.93 micromol/L in HAPE-p (p < 0.0001). Genotype distribution of G894T and 4b/4a polymorphisms was significantly different in the two groups (p = 0.001 and 0.009, respectively). Haplotype analysis revealed -922A/G and -786T/C polymorphisms in complete linkage disequilibrium. The wild-type haplotypes G-b (G894T, 4b/4a), G-A (G894T, -922A/G), and G-b-A (G894T, 4b/4a, -922A/G) were significantly overrepresented in HAPE-r (p < 0.0001, p = 0.03, and p = 0.02, respectively). The heterozygote genotype combination GTba as compared to wild-type combination GGbb was significantly higher in HAPE-p (chi2 = 18.62, p = 0.00009; odds ratio, 7.20; 95% confidence interval, 2.82 to 18.38). The combination of four heterozygotes GTbaAGTC was overrepresented in HAPE-p (p = 0.04), whereas the wild-type genotype combination GGbbAATT was overrepresented in HAPE-r (p = 0.002). Furthermore, the GGbb combination correlated with significantly elevated NOx as compared to remaining combinations as a whole in both HAPE-r and HAPE-p (p = 0.01 and 0.004, respectively).']
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['Oesophageal adenocarcinomas often show resistances to chemotherapy (CTX), therefore, it would be of high interest to better understand the mechanisms of resistance. We examined the expression of heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) in pretherapeutic biopsies of oesophageal adenocarcinomas to assess their potential role in CTX response.', 'Ninety biopsies of locally advanced adenocarcinomas before platin/5-fluorouracil (FU)-based CTX were investigated by reverse phase protein arrays (RPPAs), immunohistochemistry (IHC) and quantitative RT-PCR.', 'CTX response strongly correlated with survival (P=0.001). Two groups of tumours with specific protein expression patterns were identified by RPPA: Group A was characterised by low expression of HSP90, HSP27 and p-HSP27((Ser15, Ser78, Ser82)) and high expression of GRP78, GRP94, HSP70 and HSP60; Group B exhibited the inverse pattern. Tumours of Group A were more likely to respond to CTX, resulting in histopathological tumour regression (P=0.041) and post-therapeutic down-categorisation from cT3 to ypT0-T2 (P=0.040). High HSP60 protein (IHC) and mRNA expression were also associated with tumour down-categorisation (P=0.016 and P=0.004).']
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['To study the nonlinearity of myocardial signal intensity and gadolinium contrast concentration during first-pass perfusion MRI, and to compare quantitative perfusion estimates using nonlinear myocardial signal intensity correction.', 'The nonlinearity of signal intensity and contrast concentration was simulated by magnetization modeling and evaluated in phantom measurements. A total of 10 healthy volunteers underwent rest and stress dual-bolus perfusion studies using an echo-planar imaging sequence at both short and long saturation-recovery delay times (TD70 and TD150). Perfusion estimates were compared before and after the correction.', 'The phantom data showed a linear relationship (R(2) = 1.00 and 0.99) of corrected signal intensity vs. contrast concentrations. Peak myocardial contrast concentration averaged 0.64 +/- 0.10 mmol x L(-1) at rest and 0.91 +/- 0.21 mmol x L(-1) during stress for TD70 and were similar for TD150 (P = not significant [NS]). The corrections were larger for stress than rest perfusion and larger for TD150 than TD70 studies (both P < 0.01). Perfusion estimates of TD70 and TD150 stress studies were significantly different before the correction (P < 0.01) but equivalent after the correction (P = NS).']
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["Fibroblast growth factor 21 (FGF21) has been demonstrated to be a metabolic regulator with beneficial effects. Several studies have shown that type 2 diabetes mellitus (T2DM) patients have increased FGF21 levels and decreased expression of FGF receptors, suggesting a state of 'FGF21 resistance'. The aim of this study was to investigate the effects of the glucagon-like peptide (GLP)-1 receptor agonist exenatide on FGF21 levels and other metabolic parameters in patients with newly diagnosed T2DM.", 'A total of 100 participants, comprising 47 newly diagnosed T2DM patients and 53 age-matched healthy controls, were recruited. T2DM patients were assigned to 12 weeks of exenatide treatment. Their FGF21 levels and other metabolic parameters were measured before and after exenatide treatment.', 'T2DM patients had significantly higher FGF21 levels than the controls. No difference in FGF21 was found between overweight and non-overweight control subgroups. In T2DM patients, exenatide treatment resulted in decreases in BMI, HbA']
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['This study assessed the acute effect of ethanol on GABAergic transmission at molecular layer interneurons (MLIs; i.e. basket and stellate cells) in the cerebellar cortex. The actions of ethanol on spontaneous firing of these pacemaker neurons were also measured.', 'Transgenic mice (glutamic acid-decarboxylase 67-green fluorescent protein knock-in mice) that express green fluorescence protein in GABAergic interneurons were used to aid in the identification of MLIs. Parasagittal cerebellar slices were prepared and whole-cell patch-clamp electrophysiological techniques were used to measure GABA(A) receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Loose-seal cell-attached recordings were used to measure spontaneous action potential firing.', 'Stellate cells received spontaneous GABAergic input in the form of a mixture of action potential-dependent events (sIPSCs) and quantal events (mIPSCs); ethanol increased sIPSC frequency to a greater extent than mIPSC frequency. Ethanol increased spontaneous action potential firing of MLIs, which could explain the increase in sIPSC frequency in stellate cells. Basket cells received GABAergic input in the form of quantal events only. Ethanol significantly increased the frequency of these events, which may be mediated by a different type of interneuron (perhaps, the Lugaro cell) or Purkinje cell collaterals.']
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['Multipotent mesenchymal stromal cells (MMSCs) are minimally differentiated precursors with great potential to transdifferentiate. These cells are quite resistant to oxygen limitation, suggesting that a hypoxic milieu can be physiological for MMSCs.', 'Human MMSCs isolated from adipose tissue were grown at various oxygen concentrations. Alteration in cell immunophenotype was determined by flow cytometry after staining with specific antibodies. Concentrations of glucose and lactate were determined using the Biocon colorimetric test. Cellular respiration was assessed using oxygen electrode. The modes of cell death were analyzed by flow cytometry after staining with Annexin V and propidium iodide.', "We found that permanent oxygen deprivation attenuated cellular ATP levels in these cells, diminishing mitochondrial ATP production but stimulating glycolytic ATP production. At the same time, permanent hypoxia did not affect MMSCs' viability, stimulated their proliferation and reduced their capacity to differentiate. Further, permanent hypoxia decreased spontaneous cell death by MMSCs."]
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['While several studies suggest that traffic-related air pollutants are detrimental for respiratory health, few studies have examined relationships between residential proximity to a major roadway and asthma control in children. Furthermore, a major limitation of existing research is reliance on self-reported outcomes. We therefore determined the spatial relationship between the distance from a major roadway and clinical, physiologic and inflammatory features of asthma in a highly characterized sample of asthmatic children 6-17 years of age across a wide range of severities. We hypothesized that a closer residential proximity to a major roadway would be associated with increased respiratory symptoms, altered pulmonary function and a greater magnitude of airway and systemic inflammation.', '224 children 6-17 years with confirmed asthma completed questionnaires and underwent spirometry, plethysmography, exhaled nitric oxide determination, exhaled breath condensate collection and venipuncture. Residential distance from a major roadway was determined by mapping the geographic coordinates of the residential address in Geographic Information System software. The distance between the home address and the nearest major roadway was calculated according to the shortest distance between the two points (i.e., "as the crow flies"). Asthmatic children living in closer proximity to a major roadway had an increased frequency of wheezing associated with increased medication requirements and more hospitalizations even after controlling for potential confounders. These children also had increased airway resistance, increased airway inflammation reflected by a lower breath condensate pH, and higher plasma EGF concentrations.']
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['CC chemokine ligand 18 (CCL18) promotes malignant behaviors of various human cancer types. However, its involvement in human prostate cancer has not been fully elucidated. The aim of this study was to investigate the role of CCL18 in PCa.', 'Expression of CCL18 at mRNA and protein levels was detected using real-time qRT-PCR and immunohistochemistry analysis. We analyzed the associations of CCL18 expression with clinical features of human PCa. The effects of PCa cell migration, invasion, and apoptosis were tested. The efficiency of CCL18 on prostate tumor growth was assessed in a subcutaneous xenograft model.', 'CCL18 expression was upregulated (both P < 0.01) in PCa tissues compared with those in noncancerous prostate tissues. CCL18 upregulation was correlated with high Gleason score (P = 0.034) of patients with PCa. rCCL18 stimulation in PCa cells promoted cell migration and invasion but decreased DU145 cells apoptosis rate. Furthermore, subcutaneous homografts models showed the increased tumor growth and tumor vascularization with the CCL18 stimulation, and the expression of Ki67, PCNA, and CD31 in CCL18 stimulation mice was also significantly increased.']
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['Aberrant signaling pathways leads to cancer initiation and progression. Both Notch and PI3K/AKT signaling pathways are believed to be involved in prostate cancer. How the interaction between the two pathways contributes to prostate cancer progression to androgen independence is still elusive.', 'Prostate cancer cells were grown in RPMI 1,640 supplemented with 10% heat-inactivated fetal bovine serum (FBS) or 10% charcoal-stripped heat-inactivated fetal bovine serum (FCS), 1% penicillin-streptomycin in 75\u2009cm2 polystyrene flasks, and maintained at 37 °C in a humidified atmosphere with 5% CO2 . Cell proliferation, invasion were performed with cell counting, matrigel assay in vitro. Dual luciferase assays were performed using reporter plasmids with ARE (Androgen Response Element, ARE). RNA interference was applied to gene silence. Tumorigenicity of cancer cells was evaluated by mouse xenograft in vivo.', 'A subpopulation of casodex resistant prostate cancer cells were identified with an overexpressed androgen receptor (AR) and aggressive phenotypes, characterized with high proliferation, invasion in vitro and enhanced tumorigenesis in vivo. Gene profiling for androgen-dependent LNCaP and androgen-independent LNCaP-CR revealed that both CSL and AKT gave the similar expressional pattern upon casodex treatment. Immunoblot demonstrated that CSL and AKT were dramatically suppressed in androgen dependent LNCaP cells, but slightly inhibited in LNCaP-CR cells as well as other androgen independent prostate cancer cells. Further studies indicated that CSL regulates AKT, and subsequently AR in prostate cancer cells. AKT mediates casodex resistance and androgen independence through regulation of cyclin D1.']
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['The Emergency Severity Index (ESI) is a new five-level triage instrument. The objective of this study was to determine whether there is an association between ESI triage status and short-term survival.', 'This was a survival analysis for a population-based, stratified random sample of patients over the age of 14 years who visited an urban, university-affiliated hospital emergency department (ED). Measures included ESI triage category (1 through 5), vital status obtained from the Social Security Administration, date of death (if applicable), and survival time in days. Data were analyzed with Kaplan-Meier survival analysis.', 'Eighty-seven percent (202/232) of a random sample of patients appeared in the Social Security vital status registry. During the 252-day follow-up period, 19 patients (9%) died, 161 (80%) lived, and 22 (11%) had an unknown vital status. The ESI triage level was strongly associated with vital status at six months (Kaplan-Meier chi-square 25.9, p<0.0001). No patient in triage categories 4 and 5 died (lower limits of the 95% confidence interval for survival, 92% and 93%, respectively); whereas survival in triage category 1 was 68%, and in categories 2 and 3 it was 86% and 83%, respectively. Most of the deaths occurred within 60 days after the index ED visit. Sensitivity analyses biased against the instrument continued to demonstrate the association between triage status and survival.']
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['Neurodegenerative diseases are a major problem afflicting ageing populations; however, there are no effective treatments to stop their progression. Oxidative stress and neuroinflammation are common factors in their pathogenesis. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the master regulator of oxidative stress, and melatonin is an endogenous hormone with antioxidative properties that reduces its levels with ageing. We have designed a new compound that combines the effects of melatonin with Nrf2 induction properties, with the idea of achieving improved neuroprotective properties.', 'Compound ITH12674 is a hybrid of melatonin and sulforaphane designed to exert a dual drug-prodrug mechanism of action. We obtained the proposed hybrid in a single step. To test its neuroprotective properties, we used different in vitro models of oxidative stress related to neurodegenerative diseases and brain ischaemia.', 'ITH12674 showed an improved neuroprotective profile compared to that of melatonin and sulforaphane. ITH12674 (i) mediated a concentration-dependent protective effect in cortical neurons subjected to oxidative stress; (ii) decreased reactive oxygen species production; (iii) augmented GSH concentrations in cortical neurons; (iv) enhanced the Nrf2-antioxidant response element transcriptional response in transfected HEK293T cells; and (v) protected organotypic cultures of hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation from stress by increasing the expression of haem oxygenase-1 and reducing free radical production.']
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['Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). Polyamine concentrations are elevated in colorectal cancer. Depletion of polyamine content in colorectal cancer by chemotherapy is related to tumor regression and impaired tumorigenicity. The current study evaluates the therapeutic effects of antisense ODC and AdoMetDC sequences on colorectal cancer in vitro and in vivo.', 'Antisense ODC and AdoMetDC sequences were cloned into an adenoviral vector (Ad-ODC-AdoMetDCas). The human colon cancer cell lines, HT-29 and Caco-2, were infected with Ad-ODC-AdoMetDCas as well as with control vector. Viable cell counting, determination of polyamine concentrations, cell cycle analysis, and Matrigel invasion assays were performed in order to assess properties of tumor growth and invasiveness. Furthermore, the antitumor effects of Ad-ODC-AdoMetDCas were also evaluated in vivo in a nude mouse tumor model.', 'Our study demonstrated that adenovirus-mediated ODC and AdoMetDC antisense expression inhibits tumor cell growth through a blockade of the polyamine synthesis pathway. This inhibitory effect cannot be reversed by the administration of putrescine. Tumor cells were arrested at the G1 phase of the cell cycle after gene transfer and had reduced invasiveness. The adenovirus also induced tumor regression in established tumors in nude mice.']
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['Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery.', 'Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort.']
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['Research was conducted to assess multichannel saliency with the Ineraid cochlear prosthesis. The goal was to determine whether tonotopically ordered stimulation benefits speech reception.', "In a single high-performing subject, changes in speech reception were studied during two dramatic alterations to the normal (tonotopic) mapping between the sound-processors's four filter channels and the intracochlear electrode array: In one alteration, the four filter outputs were summed and delivered to one electrode; this single-channel mapping was worn for 7 days. In another alteration, the four filter outputs were connected in reverse tonotopic order to four intracochlear electrodes; this reversed mapping was worn for 3 days.", 'When using the implant in conjunction with speechreading, all three mappings provided large gains over speechreading alone on the recognition of words in sentences. When using the implant alone (without speechreading), tests of consonant and vowel recognition, and the recognition of words in isolation and in sentences all showed substantial decreases in performance across the three mapping conditions: normal > single-channel > reversed. The patterns of segmental confusions and the relations among scores on different tests were highly consistent. Finally, the performance with the altered mappings was, in some ways, remarkably good. With single-channel mapping, 15% word recognition was obtained, much less than the 54% obtained with the normal mapping, but demonstrative of some open-set speech reception. With the reversed mapping, high levels of consonantal voicing and manner information were received, indicating good reception of time-intensity cues, but open-set word recognition was near zero.']
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['Insulin resistance, decreased response of peripheral tissue to normal insulin levels, is known to be related to cardiometabolic diseases. Cardiopulmonary fitness is also considered to be related to these comorbidities. Therefore, we investigated the relationship between insulin resistance and cardiopulmonary fitness by performing a 3-minute step test in a Korean non-diabetes mellitus (DM) population.', 'A total of 118 non-DM subjects were enrolled during their routine health check-up. Insulin resistance was measured by calculating homeostatic model assessment-insulin resistance (HOMA-IR), and a 3-minute step test was performed to measure cardiopulmonary fitness.', 'Post-60 seconds exercise heart rate after 3-minute test (R60 heart rate) was correlated with age (r = -0.21, P = 0.02), education (r = 0.17, P = 0.04), body mass index (r = 0.23, P = 0.01), waist circumference (r = 0.28, P < 0.01), fasting insulin (r = 0.28, P < 0.01), HOMA-IR (r = 0.25, P < 0.01), low density lipoprotein-cholesterol (r = 0.28, P < 0.01), high sensitivity C-reactive protein levels (r = 0.22, P = 0.02), and baseline heart rate (r = 0.56, P < 0.01). In a step-wise multiple regression analysis, baseline heart rate (β = 0.79, P < 0.001), HOMA-IR (β = 0.65, P = 0.02), and systolic blood pressure (β = 0.15, P = 0.03) were identified as explanatory variables for R60 heart rates.']
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['During allergic lung inflammation dendritic cells (DCs) direct the generation and function of effector T-helper type 2 cells. T-helper type 2 cells not only orchestrate the inflammatory processes in the tissue by inducing the accumulation and activation of proinflammatory cells but also induce IgE production by B cells. Thus, inhibitors of DC function should have therapeutic benefits in patients with allergies.', 'VAF347, a novel low molecular weight immunomodulator, is described and acts as an antiinflammatory compound by a dual mode of action.', 'VAF347 inhibited the function of human monocyte-derived DCs to induce T-cell proliferation and cytokine production. Mechanistically, this effect may be due to reduced expression of CD86, HLA-DR, and interleukin 6 by DCs. In addition, the compound inhibited IgE synthesis in an isotype-specific fashion by human B lymphocytes. In a mouse model of antigen-induced eosinophilic inflammation, VAF347 blocked lung eosinophilia, mucus hyperplasia, and serum IgE levels, representing the hallmarks of allergic lung inflammation. The biological effects in vivo are most likely mediated by the immunoregulatory role of VAF347 on DCs because allergic lung inflammation was also inhibited in B-cell-deficient mice.']
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['The bacterium Pseudomonas syringae pv. syringae (Pss) is a pathogen of many plant species and causes, for example, brown spot disease in bean plants (Phaseolus vulgaris). Pss excretes the syringolins, natural product molecules that act as a virulence factors and inhibit the proteasome of the host plants.', 'Proteasome inhibitors belong to an important class of anticancer agents and bortezomib (Velcade(®)) has been Food and Drug Administration-approved for the treatment of multiple myeloma (MM) and mantle cell lymphoma. Syringolins represent a new class of proteasome inhibitors and the present work was undertaken to design a potent syringolin-inspired analogue (TIR-203) for anticancer drug development.', 'TIR-203 was tested against human MM and neuroblastoma (NB) cells. Cancer cells were treated with TIR-203 at various concentrations (0-10 µM) and the cell viability was measured using the MTS assay. To determine the effects on proteasomal activities, the cell culture-based proteasome inhibition assay was used. Syringolin A (SylA) and bortezomib were included as controls.', 'TIR-203 inhibited the cell proliferation of MM and NB cells in a dose-dependent manner at significantly lower concentrations than SylA. In MM cells, TIR-203 effectively inhibited the chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) activities of the proteasome. In NB cells, TIR-203 inhibited the CT-L and C-L activities, but not the T-L activity.']
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['To expand the clinical use of botulinum toxin A (BTX-A) in treating patients with small prostates and symptomatic benign prostatic hyperplasia (BPH). BTX-A injection into the prostate in patients with voiding dysfunction and large prostates has been reported.', 'Sixteen men with symptomatic BPH, a prostate volume less than 30 cm3, peak flow rate less than 12 mL/s, and with refractory disease after at least 1 month of alpha-blocker treatment received BTX-A 100 U injection into the prostate transperineally under transrectal ultrasound guidance. The clinical effects were evaluated at baseline and after treatment.', 'No significant local or systemic side effects were observed in any of the patients. All patients reported subjective improvement starting at approximately 1 week and achieved a maximal effect after 1 month that was maintained at 3 and 6 months. At 6 to 12 months (mean 10) of follow-up, no patient had symptom recurrence. The mean prostate volume, symptom score, and quality-of-life index were significantly reduced by 13.3% (from 19.6 +/- 1.2 to 17.0 +/- 1.1 cm3), 52.6% (from 18.8 +/- 1.6 to 8.9 +/- 1.9), and 44.7% (from 3.8 +/- 0.3 to 2.1 +/- 0.3), respectively. The maximal flow rate increased significantly by 39.8% (from 7.3 +/- 0.7 to 11.8 +/- 0.8 mL/s). In 2 patients who underwent biopsy 1 month after BTX-A injection, terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick end labeling staining demonstrated an increase in apoptotic activity, not only in the glandular component, but also in the stromal component of the prostatic tissue.']
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['Chitin is a ubiquitous polysaccharide in fungi, insects, allergens, and parasites that is released at sites of infection. Its role in the generation of tissue inflammation, however, is not fully understood.', 'We hypothesized that chitin is an important adjuvant for adaptive immunity.', 'Mice were injected with a solution of ovalbumin and chitin.', 'We used in vivo and ex vivo/in vitro approaches to characterize the ability of chitin fragments to foster adaptive immune responses against ovalbumin and compared these responses to those induced by aluminum hydroxide (alum). In vivo, ovalbumin challenge caused an eosinophil-rich pulmonary inflammatory response, Th2 cytokine elaboration, IgE induction, and mucus metaplasia in mice that had been sensitized with ovalbumin plus chitin or ovalbumin plus alum. Toll-like receptor-2, MyD88, and IL-17A played critical roles in the chitin-induced responses, and MyD88 and IL-17A played critical roles in the alum-induced responses. In vitro, CD4(+) T cells from mice sensitized with ovalbumin plus chitin were incubated with ovalbumin-stimulated bone marrow-derived dendritic cells. In these experiments, CD4(+) T-cell proliferation, IL-5, IL-13, IFN-γ, and IL-17A production were appreciated. Toll-like receptor-2, MyD88, and IL-17A played critical roles in these in vitro adjuvant properties of chitin. TLR-2 was required for cell proliferation, whereas IL-17 and TLR-2 were required for cytokine elaboration. IL-17A also inhibited the generation of adaptive Th1 responses.']
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['Mutations in the p53 tumor suppressor gene are generally believed to be a late event in the progression of prostate cancer, and are associated with androgen-independence, increased angiogenesis, metastasis, recurrence, and a worse prognosis. In this review, we examine the current literature available on p53 mutations found in prostate cancer and focus on stages A (T1) and B (T2) of the disease. The alteration of genes involved in p53 regulation are also examined, as well as animal models that support an early role for p53 in the initiation and development of prostate cancer.', 'We report here that p53 mutations occur in approximately one third of early stage prostate cancers and that expression of HPV E6 or over-expression of mdm2 contributes to loss of p53 function in an additional 25% of organ-confined disease. High levels of p53 mutation are found in normal prostate tissue of prostate cancer patients and in the precursor lesion, prostatic intraepithelial neoplasia, further implicating p53 mutation or loss as an early event in prostate tumorigenesis.']
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['The dyslipidemia of type 2 diabetes mellitus has multiple etiologies and impairs lipoprotein functionality, thereby increasing risk for cardiovascular disease. High-density lipoproteins (HDLs) have several beneficial effects, notably protecting the heart from myocardial ischemia. We hypothesized that glycation of HDL could compromise this cardioprotective effect.', 'We used in vitro (cardiomyocytes) and ex vivo (whole heart) models subjected to oxidative stress together with HDL isolated from diabetic patients and nondiabetic HDL glycated in vitro (methylglyoxal). Diabetic and in vitro glycated HDL were less effective (P<0.05) than control HDL in protecting from oxidative stress. Protection was significantly, inversely correlated with the degree of in vitro glycation (P<0.001) and the levels of hemoglobin A1c in diabetic patients (P<0.007). The ability to activate protective, intracellular survival pathways involving Akt, Stat3, and Erk1/2 was significantly reduced (P<0.05) using glycated HDL. Glycation reduced the sphingosine-1-phosphate (S1P) content of HDL, whereas the S1P concentrations of diabetic HDL were inversely correlated with hemoglobin A1c (P<0.005). The S1P contents of in vitro glycated and diabetic HDL were significantly, positively correlated (both <0.01) with cardiomyocyte survival during oxidative stress. Adding S1P to diabetic HDL increased its S1P content and restored its cardioprotective function.']
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['Tetracyclines have been demonstrated to inhibit formation of beta-amyloid (Abeta) aggregates and to disassemble preformed fibrils. Minocycline, a semi-synthetic second-generation tetracycline, can reverse Abeta-induced impairment of cognitive functions. Since somatostatin is involved in cognition and we recently showed that Abeta(25-35) lowers somatostatin expression in the rat temporal cortex, our aim here was to analyze the effects of minocycline on somatostatin immunoreactivity and mRNA levels in the temporal cortex of Abeta(25-35)-infused and healthy rats. Moreover, since brain levels of neprilysin, an Abeta-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression.', 'Wistar rats were thus injected with minocycline twice on the first day of treatment. On the following day, and during 14 days, Abeta(25-35) or vehicle were administered. Minocycline was injected once again on days 13 and 14. All animals were sacrificed 24 h after the last drug injection.', 'Minocycline abrogated the Abeta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mRNA levels, phosphorylated-CREB content and neprilysin levels. Minocycline alone enhanced these targets.']
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['In-stent restenosis results from neointimal tissue proliferation. L-arginine supplementation improves endothelial function and reduces neointimal formation after arterial injury in animals. The aim of the study was to assess the influence of L-arginine administration on neointimal proliferation after coronary stenting in human beings.', 'We performed a prospective, randomized, double-blinded, placebo-controlled study in 60 men without diabetes. L-arginine/placebo was administered intravenously 12 hours before percutaneous coronary intervention (200 mg/kg for 240 minutes), during the procedure (200 mg/kg for 240 minutes), and intracoronarily immediately before stent implantation (500 mg for 10 minutes), and it was followed by oral treatment for next 2 weeks (6.0 g/d). By quantitative coronary angiography, late lumen loss, and intravascular ultrasound, neointimal volume and percent neointimal volume were calculated after 7 months of follow-up to assess neointimal formation.', 'There were no differences in baseline clinical or angiographic characteristics between the two groups. Intravenous infusion of L-arginine increased plasma L-arginine concentrations 6-fold compared with placebo (661 +/- 264 vs 107 +/- 71 mmol/L, P <.001). During the 2-week period of oral treatment with L-arginine there was a sustained, significant increase of plasma L-arginine level (150 +/- 50 vs 100 +/- 17, P <.001, 135 +/- 42 vs 89 +/- 27, P <.001, respectively, on days 7 and 14 in the L-arginine group vs placebo). However, at 7-month follow-up, there was no difference in neointimal formation measured both by quantitative coronary angiography and intravascular ultrasound between the study groups.']
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['We present the largest, most comprehensive, single center experience to date of minimally invasive liver resection (MILR).', 'Despite anecdotal reports of MILR, few large single center reports have examined these procedures by comparing them to their open counterparts.', 'Three hundred MILR were performed between July 2001 and November 2006 at our center for both benign and malignant conditions. These included 241 pure laparoscopic, 32 hand-assisted laparoscopic, and 27 laparoscopy-assisted open (hybrid) resections.These MILR were compared with 100 contemporaneous, cohort-matched open resections. MILR included segmentectomies (110), bisegmentectomies (63), left hepatectomies (47), right hepatectomies (64), extended right hepatectomies (8), and caudate lobe (8) resections. Benign etiologies encompassed cysts (70), hemangiomata (37), focal nodular hyperplasia (FNH) (23), adenomata (47), and 20 live donor right lobectomies. Malignant etiologies included primary (43) and metastatic (60) tumors. Hepatic fibrosis/cirrhosis was present in 25 of 103 patients with malignant diseases (24%).', 'There was high data consistency within the 3 types of MILR. MILR compared favorably with standard open techniques: operative times (99 vs. 182 minutes), blood loss (102 vs. 325 ml), transfusion requirement (2 of 300 vs. 8 of 100), length of stay (1.9 vs. 5.4 days), overall operative complications (9.3% vs. 22%), and local malignancy recurrence (2% vs. 3%). No port-site recurrences occurred. Conversion from laparoscopic to hand-assisted laparoscopic resection occurred in 20 patients (6%), with no conversions to open. No hand-assisted procedures were converted to open, but 2 laparoscopy-assisted (7%) were converted to open.']
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['Hyperinflation (HI) is performed following open endotracheal suctioning (OES), whose goals include: to stimulate a cough, recover oxygenation and improve compliance. However, it may also induce unintended consequences, including: lung stress and strain, failure to maintain high distending pressure, and subsequently cycling recruitment and derecruitment. Here, our aim was to investigate the effects of hyperinflation after repeated OES on sequential alteration of arterial oxygenation and lung injury profile using a saline lavage-induced surfactant depleted ARDS rabbit model.', 'Briefly, 30 Japanese White Rabbits were anesthetized and ventilated in pressure-controlled setting with a tidal volume of 6-8\xa0ml/kg. Animals were divided into four groups, i.e.; Control, ARDS, OES, and HI. Saline-lavage-induced lung injury was induced except for Control group. Thereafter, rabbits were ventilated with positive-end expiratory pressure (PEEP) at 10\xa0cm H2O. The ARDS group received ventilation with the same PEEP without derecruitment. As intervention, OES and HI were performed in ARDS animals. OES was performed for 15\xa0seconds at 150\xa0mm Hg, whereas HI was performed with PEEP at 0\xa0cm H2O and peak inspiratory pressure at +5\xa0cm H2O for a minute. Total duration of the experiment was for 3\xa0hours. OES and HI were performed every 15\xa0minutes from beginning of the protocol.', 'PaO2 was maintained at about 400\xa0mm Hg in both control and ARDS groups for the duration of this study, while in both OES and HI groups, PaO2 decreased continuously up to 3\xa0hours, dropped to a mean (±SD) of 226\u2009±\u200928.9 and 97.0\u2009±\u200930.7\xa0mmHg at 3\xa0h, respectively. HI group had the lowest PaO2 in the present investigation. Histological lung injury score was the highest in HI group than other three groups. Pulmonary TNF-α and IL-8 levels were the highest in HI group compared to other groups, but without significant alterations at circulatory level in all the experimental groups.']
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['Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer.', 'Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young female breast cancer patients with a 20-year follow-up indicated that in early-onset breast cancer, DEAR1 expression serves as an independent predictor of local recurrence-free survival and correlates significantly with strong family history of breast cancer and the triple-negative phenotype (ER(-), PR(-), HER-2(-)) of breast cancers with poor prognosis.']
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['To determine the relation between plasma redox status and severity of illness for patients admitted to an intensive care unit (ICU).', 'A prospective cohort study.', 'A mixed medical and surgical adult ICU with 12 beds.', 'A total of 73 consecutive patients admitted to the ICU.', 'Venous blood samples were routinely obtained within 24 hrs of admission.', 'Plasma total antioxidant capacity and lipoperoxides were measured by spectrophotometric technique at admission to the ICU. The plasma ratio total antioxidant capacity (mM)/lipoperoxides (microM) was used as an index of plasma redox status. Plasma concentration of the markers of leukocyte activation myeloperoxidase (enzyme-linked immunosorbent assay) and polymorphonuclear-elastase (immunoactivation assay) were also measured at admission to the ICU. Analysis of correlation between plasma ratio total antioxidant capacity/lipoperoxides and APACHE III score showed a negative association (p < .001, Spearman correlation test). Myeloperoxidase and polymorphonuclear-elastase correlated positively with Acute Physiology and Chronic Health Evaluation III scores (r2 = 0.58; p < .001; and r2 = 0.05; p = .035; respectively).']
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['The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker.', 'IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry.', 'Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative.']
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['Transplants cause ischemia-reperfusion (IR) injury that can affect distant organs. Liver is particularly sensitive to IR injury. The present randomized experimental study was designed to investigate a possible protective effect of sevoflurane against liver inflammatory response to lung IR in a lung upper lobe left autotransplant model.', 'Two groups (sevoflurane and control) of eight swines each were submitted to upper lobe left lung autotransplant. Hypnotic maintenance was performed with sevoflurane 3% or propofol 8 to 10 mg/kg per hr until pneumonectomy was done; then propofol was used for all animals. Blood and liver samples were taken in four different moments: prepneumonectomy, prereperfusion, 10 min postreperfusion and 30 min postreperfusion to measure levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, nuclear factor (NF)-κB, C-reactive protein, ferritin and caspase 3. Non-parametric test was used to find statistical meaning.', 'Lung IR markedly increased the expression of TNF-α, IL-1β, MCP-1, NF-κB and caspase activity in control livers compared with basal levels, whereas liver IL-10 expression decreased 10 and 30 min post-reperfusion. Sevoflurane significantly decreased TNF-α, IL-1β, MCP-1, NF-κB liver expression and caspase 3 activity. Sevoflurane also reverted the lung IR-induced decrease in IL-10 expression.']
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['To compare the inter-day reproducibility of post-occlusive reactive hyperaemia (PORH) and sympathetic vasomotor reflexes assessed by single-point laser Doppler flowmetry (SP-LDF), integrating-probe LDF (IP-LDF) and laser speckle contrast imaging (LSCI), and the spatial variability of PORH assessed by IP-LDF and LSCI. We also evaluated the relationship between IP-LDF and LSCI perfusion values across a broad range of skin blood flows.', 'Eighteen healthy adults (50% male, age 27 ± 4 years) participated in this study. Using SP-LDF, IP-LDF and LSCI, indices of skin blood flow were measured on the forearm during PORH (1-, 5- and 10-min occlusions) and on the finger pad during inspiratory gasp and cold pressor tests. These tests were repeated 3-7 days later. Data were converted to cutaneous vascular conductance (CVC; laser Doppler flow/mean arterial pressure) and expressed as absolute and relative changes from pre-stimulus CVC (ΔCVC(ABS) and ΔCVC(REL), respectively), as well as normalised to peak CVC for the PORH tests. Reproducibility was expressed as within-subjects coefficients of variation (CV, in %) and intraclass correlation coefficients.', 'The reproducibility of PORH on the forearm was poorer when assessed with SP-LDF and IP-LDF compared to LSCI (e.g., CV for 5-min PORH ΔCVC(ABS)=35%, 27% and 19%, respectively), with no superior method of data expression. In contrast, the reproducibility of the inspiratory gasp and cold pressor test responses on the finger pad were better with SP-LDF and IP-LDF compared to LSCI (e.g., CV for inspiratory gasp ΔCVC(REL)=13%, 7% and 19%, respectively). The spatial variability of PORH responses was poorer with IP-LDF compared to LSCI (e.g., CV ranging 11-35% versus 3-16%, respectively). The association between simultaneous LSCI and IP-LDF perfusion values was non-linear.']
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["The adaptive deep brain stimulation (aDBS) controlled by local field potentials (LFPs) is considered a promising treatment for advanced Parkinson's disease (PD). The clinical research investigating aDBS functioning is currently performed using external DBS systems that require LFP recording through the temporary externalisation of DBS leads. Although research examining LFP was first undertaken more than twenty years ago, only a small number of studies concern leads' externalisation and LFP recording safety. In the present retrospective study, we assessed the risk of infection related to these procedures.", "A total of 105 patients with PD who underwent DBS surgery and leads' externalisation at our hospital from 2002 to 2014 were included in the present study. The medical records were used to collect clinical data and information concerning surgical site infections. We assessed the infection incidence in our cohort and the infection's risk related to the LFP recording procedure.", "The incidence of infections in patients who underwent leads' externalisation was 2.8%, which was consistent with the postoperative infectious risk reported in the literature (Wilcoxon Signed Rank Test, p>0.05). Moreover, the LFP recording procedure did not significantly increase the infection risk (LFP recordings vs no LFP recordings: 2.5% vs 4.2%; Fisher exact test, p>0.05)."]
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['A simple test method was developed to determine the coefficient of thermal expansion of prevailing restorative resin composites and to study the transient behavior as a function of temperature and repeated thermocycles.', "Strain gauges were used to determine the thermal expansion for seven commonly used restorative resin composites by measuring the instantaneous strain along with temperature change. The temperature was measured by means of a thermocouple, the tip of which was embedded in the composite. The differences among the test groups were analyzed using ANOVA, followed by Scheffé's multiple comparisons test.", 'The coefficient of thermal expansion determined for the composites tested was: 22.5 +/- 1.4 x 10(-6)/degree C (Z-100), 23.5 +/- 1.4 x 10(-6)/degree C (P-50), 32.6 +/- 1.6 x 10(-6)/degree C (Herculite XR), 34.1 +/- 1.8 x 10(-6)/degree C (APH), 35.4 +/- 1.4 x 10(-6)/degree C (Conquest), 41.6 +/- 1.5 x 10(-6)/degree C (Silux Plus), 44.7 +/- 1.2 x 10(-6)/degree C (Heliomolar). The coefficient was almost linear in the considered temperature range (26-75 degrees C) for all composites (r > 0.99) and decreased with each consecutive thermocycle (p < 0.1).']
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['Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria.', 'To model mucosal DC development, we isolated and cultured cell-depleted human stroma/extracellular matrix from fresh gastric and intestinal mucosa to generate stroma-conditioned media. We then analyzed the capacity of stroma-conditioned media-treated monocyte-derived DCs and primary human gastric and intestinal DCs pulsed in vitro with H pylori to induce T-cell proliferation and interferon gamma secretion.', 'Stromal factors in gastric mucosa suppressed H pylori-stimulated DC activation and the ability of DCs to drive a Th1 proliferative and cytokine response to H pylori. The ability of gastric stromal factors to down-regulate DC function was similar to that of intestinal stromal factors and was independent of transforming growth factor β, prostaglandin E₂, interleukin (IL)-10, and thymic stromal lymphopoietin. Stroma-conditioned media-induced reduction in DC-stimulated Th1 responses was associated with reduced DC release of IL-12.']
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['Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor.', 'A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR.', 'Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P <0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8%, and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs.']
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['A number of different surgical procedures have been developed to treat Achilles tendon injuries including open and mini-invasive type. The aim of the present work was to compare the functional outcome of two different techniques, applying a clinical and instrumented protocol.', "Fifty-one subjects were enrolled in the study. The experimental group consisted of 34 patients with a ruptured Achilles tendon, 19 operated by open surgical reconstruction without reinforcement (Open Group), while 15 underwent a mini-invasive procedure (Mini-invasive Group); the Control Group consisted of 17 healthy subjects. The assessment was based on the standing vertical jump, in both 'countermovement jump' and 'squat jump' mode, studying the relative flight times and the coordination of movement of each limb. An accelerometer was fastened to each ankle to obtain an independent assessment of the movement of each limb.", "The surgically treated patients showed a comparable functional performance to that of the Control Group but despite this full recovery they showed a tendency to ''favor'' the affected limb. This finding was more marked in the Mini-invasive Group. The Control Group invariably showed better coordination of the movement of the two limbs than the two experimental groups. This was particularly apparent in the take-off phase, indicated by asymmetrical push-off of the two limbs."]
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['Chitinases are enzymes that cleave chitin, which is present in fungal cells. Two types of human chitinases, chitotriosidase and acidic mammalian chitinase, and the chitinase-like protein, YKL-40, seem to play an important role in asthma. We hypothesized that exposure to environmental fungi may modulate the effect of chitinases in individuals with asthma.', 'To explore whether interactions between high fungal exposure and common genetic variants in the two chitinases in humans, CHIT1 and CHIA, and the chitinase 3-like 1 gene, CHI3L1, are associated with severe asthma exacerbations and other asthma-related outcomes.', 'Forty-eight single nucleotide polymorphisms (SNPs) in CHIT1, CHIA, and CHI3L1 and one CHIT1 duplication were genotyped in 395 subjects and their parents as part of the Childhood Asthma Management Program. Household levels of mold (an index of fungal exposure) were determined on house dust samples. We conducted family-based association tests with gene-environment interactions. Our outcome was severe exacerbation, defined as emergency department visits and hospitalizations from asthma over a 4-year period, and our secondary outcomes included indices of lung function and allergy-related phenotypes.', 'Of the 395 subjects who had mold levels at randomization, 24% (95 subjects) had levels that were greater than 25,000 units per gram of house dust (high mold exposure). High mold exposure significantly modified the relation between three SNPs in CHIT1 (rs2486953, rs4950936, and rs1417149) and severe exacerbations (P for interaction 0.0010 for rs2486953, 0.0008 for rs4950936, and 0.0005 for rs1417149). High mold exposure did not significantly modify the relationship between any of the other variants and outcomes.']
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['Sevoflurane is produced by several manufacturers. Currently marketed sevoflurane formulations differ in their method of synthesis, impurities, containers in which they are sold, and water content. Of the various types of chemical degradation to which sevoflurane is susceptible, the most pertinent is degradation by Lewis acids (such as metal oxides and metal halides) to hydrofluoric acid and other toxic compounds. Water inhibits such degradation. This observational study determined the degradation profile of three formulations of sevoflurane (two lower-water and one higher-water formulation) when stored in three types of vaporizers.', 'Lower-water sevoflurane (Eraldin, Laboratorios Richmond/Minrad, Argentina [19 ppm water] and generic sevoflurane, Baxter, US [57 ppm water]) and higher-water sevoflurane formulations (Ultane, Abbott, US [352 ppm water]) were stored in three different vaporizers (Draeger Vapor 2000, GE/Datex-Ohmeda Tec 7, Penlon Sigma Delta) under accelerated storage conditions (40 degrees C). Sevoflurane was sampled from each vaporizer immediately following filling and after 1, 2, and 3 wk, and analyzed for water content, pH, fluoride, and total degradants.', 'Lower-water sevoflurane formulations stored in the Penlon Sigma Delta vaporizers contained time dependent increases in hydrofluoric acid (pH decreased as low as 3, fluoride concentration as high as 600 ppm), and total degradants (>68,000 ppm). Penlon Sigma Delta vaporizers filled with lower-water sevoflurane formulations showed substantial etching of the sight glass and metal filler shoe after 3 wk of storage. The higher-water sevoflurane formulation (Ultane, Abbott, US [352 ppm water]) contained negligible amounts of fluoride or degradants, and small decreases in pH. Sevoflurane stored in Draeger Vapor 2000 and GE/Datex-Ohmeda Tec 7 showed negligible changes in pH, fluoride concentration, and degradants.']
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['Sustained cardiac pressure overload-induced hypertrophy and pathological remodeling frequently leads to heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) has been identified to be an important regulator of cell proliferation, differentiation, and apoptosis. However, the physiological role of CKIP-1 in the heart is unknown.', 'The results of echocardiography and histology demonstrate that CKIP-1-deficient mice exhibit spontaneous cardiac hypertrophy with aging and hypersensitivity to pressure overload-induced pathological cardiac hypertrophy, as well. Transgenic mice with cardiac-specific overexpression of CKIP-1 showed resistance to cardiac hypertrophy in response to pressure overload. The results of GST pull-down and coimmunoprecipitation assays showed the interaction between CKIP-1 and histone deacetylase 4 (HDAC4), through which they synergistically inhibited transcriptional activity of myocyte-specific enhancer factor 2C. By directly interacting with the catalytic subunit of phosphatase 2A, CKIP-1 overexpression enhanced the binding of catalytic subunit of phosphatase-2A to HDAC4 and promoted HDAC4 dephosphorylation.']
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['To compare CSF filtration (CSFF) and plasma exchange (PE) in the treatment of patients with Guillain-Barré syndrome (GBS).', 'In a prospective controlled clinical trial, 37 patients with acute GBS were randomized to receive either CSFF or PE. Inclusion criteria were fulfillment of National Institute of Neurological and Communicative Disorders and Stroke criteria and disability to walk >5 m unassisted.', 'With similar baseline features in both groups (initial disability grades on the six-point grading scale of the GBS Study Group) the primary outcome variable (improvement within 28 days after randomization) was almost identical (test for equivalence p = 0.0014), the mean grade values being 0.82 in the CSFF group and 0.80 in the PE group. After 56 days, 56% (9 of 16 patients) of the CSFF group and 37% (7 of 19 patients) of the PE group had reached grade 2 (i.e., ability of unassisted walking >5 m). After 6 months, the probability to reach grade 2 was about 80% in both groups. In the CSFF group, transient pleocytosis occurred without apparent clinical complications. Clinically relevant complications were higher in the PE-treated group.']
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['The evidence for the efficacy of D-cycloserine (DCS) for augmenting cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided by preclinical research and initial findings from a small-scale study involving humans, we tested the hypothesis that DCS enhancement of exposure therapy would be specific to successful exposure sessions.', 'Medication-free adults with generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1 h before each of 5 exposure sessions that were part of a standardized 12-session group CBT protocol. Participants provided fear ratings at the beginning and just before the end of exposure exercises. Independent raters, blind to group assignment, administered the clinical global impression improvement and severity scales at each session and at posttreatment.', 'Mixed-effects analyses revealed that, among patients who reported low fear at the end of an exposure session, those who had received DCS evidenced significantly greater clinical improvement at the next session, relative to those who had received placebo. In contrast, when exposure end fear was high, patients receiving DCS exhibited less clinical improvement at the following session than patients receiving placebo. Similarly, patients who had received DCS evidenced lower clinical severity at posttreatment, relative to patients who had received placebo, only when their average end fear for medication-augmented sessions had been in the low to moderate range. Finally, these moderating effects of exposure success as indexed by end fear were not better accounted for by within-session extinction.']
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['2-Methoxyestradiol (2MEO) is being developed as a novel antitumor agent based on its antiangiogenic activity, tumor cell cytotoxicity, and apparent lack of toxicity. However, pharmacologic concentrations of 2MEO bind to estrogen receptors (ER). We have therefore examined the ER activity of 2MEO.', 'Estrogenic actions of 2MEO were evaluated by changes in gene expression of the ER-positive (MCF7) breast tumor cell line and, in vivo, estrogenicity was assessed in breast tumor xenograft models and by measuring endocrine responses in uterus and liver.', 'In the ER-positive breast tumor cell line (MCF7), microarray experiments revealed that 269 of 279 changes in gene expression common to 2MEO and estradiol were prevented by the ER antagonist, ICI 182,780. Changes in the expression of selected genes and their sensitivity to inhibition by ICI 182,780 were confirmed by quantitative reverse transcription-PCR measurement. Activation of ER in MCF7 cells by 2MEO was further confirmed by stimulation of an estrogen response element-dependent reporter gene that was blocked by ICI 182,780 (1 micromol/L). Doses of 2MEO (15-150 mg/kg) that had no antitumor efficacy in either nu/nu BALB/c or severe combined immunodeficient mice bearing ER-negative MDA-MB-435 tumors had uterotropic and hepatic estrogen-like actions. In female nu/nu BALB/c mice inoculated with the estrogen-dependent MCF7 tumor cells, 2MEO (50 mg/kg/d) supported tumor growth.']
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['Loss of mismatch repair (MMR) function in sporadic colorectal cancer occurs most commonly because of inactivation of MLH1, and it causes an increase in mutation rate. However, it is uncertain whether loss of MMR alters any other cellular function. The aim of this study was to investigate the role of MMR in regulating cell numbers and apoptosis.', "MLH1 protein levels were manipulated by (a) cloning and forcibly expressing MLH1 in HCT116 (a cell line with MLH1 mutation) and RKO (a cell line with MLH1 silencing), and (b) knockdown of MLH1 in SW480 (a cell line with normal MMR function). Cell number and apoptotic bodies were measured in standard and 'high stress' (ie, after staurosporine exposure) conditions.", 'Restoration of MLH1 function in HCT116 and RKO resulted in increased cell number (p<0.001 for both cell lines) and decreased numbers of floating apoptotic bodies (p<0.01 in HCT116) in standard culture conditions. However, on induction of apoptotic stress, restoration of MLH1 resulted in reduced cell numbers (p<0.005). Knockdown of MLH1 in SW480 had no effect on cell numbers or apoptosis.']
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['Angiotensin II (AngII) signal transduction in vascular smooth muscle cells (VSMC) is mediated by reactive oxygen species (ROS). Cyclophilin A (CyPA) is a ubiquitously expressed cytosolic protein that possesses peptidyl-prolyl cis-trans isomerase activity, scaffold function, and significantly enhances AngII-induced ROS production in VSMC. We hypothesized that CyPA regulates AngII-induced ROS generation by promoting translocation of NADPH oxidase cytosolic subunit p47phox to caveolae of the plasma membrane.', 'Overexpression of CyPA in CyPA-deficient VSMC (CyPA(-/-)VSMC) significantly increased AngII-stimulated ROS production. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors (VAS2870 or diphenylene iodonium) significantly attenuated AngII-induced ROS production in CyPA and p47phox-overexpressing CyPA(-/-)VSMC. Cell fractionation and sucrose gradient analyses showed that AngII-induced p47phox plasma membrane translocation, specifically to the caveolae, was reduced in CyPA(-/-)VSMC compared with wild-type-VSMC. Immunofluorescence studies demonstrated that AngII increased p47phox and CyPA colocalization and translocation to the plasma membrane. In addition, immunoprecipitation of CyPA followed by immunoblotting of p47phox and actin showed that AngII increased CyPA and p47phox interaction. AngII-induced p47phox and actin cell cytoskeleton association was attenuated in CyPA(-/-)VSMC. Mechanistically, inhibition of p47phox phosphorylation and phox homology domain deletion attenuated CyPA and p47phox interaction. Finally, cyclosporine A and CyPA-peptidyl-prolyl cis-trans isomerase mutant, R55A, inhibited AngII-stimulated CyPA and p47phox association in VSMC, suggesting that peptidyl-prolyl cis-trans isomerase activity was required for their interaction.']
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['We previously reported that 10 mg/day of simvastatin significantly reduced clinical scores of rheumatoid arthritis (RA) in active RA patients with hypercholesterolemia. In this study, we have investigated the mechanism by which simvastatin inhibits the production of the mediators of inflammation, such as pentraxin 3 (PTX3) and monocyte chemoattractant protein-1 (MCP-1), from fibroblast-like synoviocytes (FLS) derived from patients with RA.', 'FLS from RA patients were cultured with 0-10 μM simvastatin for 24 h. ELISA and real-time PCR were used to quantitate the protein level and the mRNA level of PTX3 and MCP-1, respectively.', 'Simvastatin both reduced the secretion of PTX3 and MCP-1 in FLS cultures and inhibited their mRNA expression in these cells. The effects of simvastatin were all completely reversed in the presence of mevalonic acid or geranylgeranylpyrophosphate, but not in the presence of farnesyl-pyrophosphate. The geranylgeranyl transferase inhibitor GGTI-298 and the Rho kinase inhibitor Y-27632 inhibited the production of PTX3 but not of MCP-1.']
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['Drug resistance can be complex, and several mutations responsible for it can co-exist in a resistant cell. Transcriptional profiling is ideally suited for studying complex resistance genotypes and has the potential to lead to novel discoveries. We generated full genome 70-mer oligonucleotide microarrays for all protein coding genes of the human protozoan parasites Leishmania major and Leishmania infantum. These arrays were used to monitor gene expression in methotrexate resistant parasites.', 'Leishmania is a eukaryotic organism with minimal control at the level of transcription initiation and few genes were differentially expressed without concomitant changes in DNA copy number. One exception was found in Leishmania major, where the expression of whole chromosomes was down-regulated. The microarrays highlighted several mechanisms by which the copy number of genes involved in resistance was altered; these include gene deletion, formation of extrachromosomal circular or linear amplicons, and the presence of supernumerary chromosomes. In the case of gene deletion or gene amplification, the rearrangements have occurred at the sites of repeated (direct or inverted) sequences. These repeats appear highly conserved in both species to facilitate the amplification of key genes during environmental changes. When direct or inverted repeats are absent in the vicinity of a gene conferring a selective advantage, Leishmania will resort to supernumerary chromosomes to increase the levels of a gene product.']
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['Much evidence suggests that plant communities on infertile soils are relatively insensitive to increased water deficit caused by increasing temperature and/or decreasing precipitation. However, a multi-decadal study of community change in the western USA does not support this conclusion. This paper tests explanations related to macroclimatic differences, overstorey effects on microclimate, variation in soil texture and plant functional traits.', 'A re-analysis was undertaken of the changes in the multi-decadal study, which concerned forest understorey communities on infertile (serpentine) and fertile soils in an aridifying climate (southern Oregan) from 1949-1951 to 2007-2008. Macroclimatic variables, overstorey cover and soil texture were used as new covariates. As an alternative measure of climate-related change, the community mean value of specific leaf area was used, a functional trait measuring drought tolerance. We investigated whether these revised analyses supported the prediction of lesser sensitivity to climate change in understorey communities on infertile serpentine soils.', 'Overstorey cover, but not macroclimate or soil texture, was a significant covariate of community change over time. It strongly buffered understorey temperatures, was correlated with less change and averaged >50 % lower on serpentine soils, thereby counteracting the lower climate sensitivity of understorey herbs on these soils. Community mean specific leaf area showed the predicted pattern of less change over time in serpentine than non-serpentine communities.']
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['Cerebral ischemia causes some disorders in behavioral patterns, including memory disorders and pain, which is due to the production of free radicals. Ferulago angulata, known in Iran as chavir, contains some bioactive compounds having antioxidant and free radical-scavenging properties.', 'This study aimed to evaluate the effect of two weeks oral administration of hydroalcoholic extract of F. angulate (100, 200 and 400 mg/kg) on pain as well as active and passive avoidance memories after permanent, bilateral common carotid artery occlusion or cerebral ischemia/hypoperfusion in male adult rats.', 'In this study, 35 male rats were randomly allocated to test and control groups. To make animal model of permanent cerebral hypoperfusion/ischemia, carotid arteries were ligatured as upper and lower and cut bilaterally.', 'It was found that the administration of 400 mg/kg hydroalcoholic extract of F. angulate for two weeks after brain hypoperfusion ischemia increased the passive avoidance memory (P < 0.001) and latency time of painful tail reflex significantly (P < 0.05).']
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['Vaginal epithelial cells (VECs) produce antimicrobial peptides including human β-defensin 2 (hBD2) and secretory leukocyte protease inhibitor (SLPI), as well as cytokines and chemokines that play vital roles in mucosal innate immunity of the female reproductive tract. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses various activities including antimicrobial activity and anti-inflammation. As inflammation and infection are commonly found in female reproductive tract, we aimed to investigate the effects of H. cordata water extract in modulating innate immune factors produced by VECs.', 'Primary human VECs were cultured and treated with H. cordata at a concentration ranging from 25-200\xa0μg/ml for 6 or 18\xa0h. After treatment, the cells and culture supernatants were harvested. The expression of hBD2 and SLPI mRNA was evaluated by quantitative real-time reverse transcription PCR. Levels of secreted hBD2 and SLPI as well as cytokines and chemokines in the supernatants were measured by ELISA and Luminex assay, respectively. Cytotoxicity of the extract on VECs was assessed by CellTiter-Blue Cell Viability Assay.', 'H. cordata did not cause measurable toxicity on VECs after exposure for 18\xa0h. The expression of hBD2 and SLPI mRNA as well as the secreted hBD2 protein were increased in response to H. cordata exposure for 18\xa0h when compared to the untreated controls. However, treatment with the extract for 6\xa0h had only slight effects on the mRNA expression of hBD2 and SLPI. The secretion of IL-2 and IL-6 proteins by VECs was also increased, while the secretion of CCL5 was decreased after treatment with the extract for 18\xa0h. Treatment with H. cordata extract had some effects on the secretion of IL-4, IL-8, CCL2, and TNF-α, but not statistically significant.']
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['The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with Plasmodium infection in central India to determine if these factors could be suitable markers of CM associated severity.', 'Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers.', 'The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission.']
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['Vascular remodeling results from aberrations in the balance between cell proliferation and death, which is seen in the obstructive vasculature of pulmonary arterial hypertension (PAH). Endothelin (ET)-1 has a potent proliferative activity on vascular smooth muscle cells, and ET receptor inhibitors are used to treat PAH; however, it remains unclear whether ET receptor inhibition contributes to the apoptosis of pulmonary arterial smooth muscle cells (PASMCs), another cause of pulmonary vascular remodeling.', 'Cultured human PASMCs were treated with the ETA receptor antagonist BQ-123 (100μM), or the ETB antagonist A-192621 (1-100μM) or BQ-788 (1-100μM) for 48h. The cells were then incubated for another 24h with or without doxorubicin (DOX, 1μM), an anthracyclin antitumor antibiotic that promotes p53-mediated apoptosis. Cell viability and apoptosis were evaluated by MTT assays, caspase-3/7 activity assays, and Western blots for cleaved caspase-3 expression.', "The viability of PASMCs was significantly decreased by A-192621 and BQ-788, in a dose-dependent manner. A-192621 and BQ-788 significantly increased the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. The PASMCs' susceptibility to DOX-induced apoptosis was significantly higher in the presence of A-192621 and BQ-788 than with vehicle. However, BQ-123 did not affect these parameters."]
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['Endothelial dysfunction is an early, pre-clinical manifestation of coronary heart disease and is associated with increased plasma levels of von Willebrand factor (vWF), soluble E-selectin, and thrombomodulin, markers of endothelial cell damage/activation and reduced nitric oxide bioavailability. Homocysteine is associated with an increased risk of cardiovascular disease and mortality. High-dose folic acid treatment lowers plasma homocysteine by 25% and improves nitric oxide bioavailability; however, the effects on other indices of endothelial cell activation/damage has not been examined in patients with coronary heart disease and normal renal function.', 'In a randomised, double-blind, cross-over study in 50 patients with coronary heart disease and normal serum creatinine, folic acid (5 mg/daily) was administered for 6 weeks and blood was analysed for von Willebrand factor, soluble E-selectin, and thrombomodulin. Endothelial nitric oxide bioavailability was assessed by flow-mediated dilatation.', 'Plasma folate levels increased (9.1+/-3.4 vs. 310+/-235 microg/l; p<0.001) and nitric oxide bioavailability improved (47+/-35 vs. 110+/-43 microm; p<0.001) following active treatment. However, markers of endothelial cell injury were not significantly influenced (von Willebrand factor 118+/-33 vs. 119+/-34%; E-selectin 52+/-17 vs. 51+/-16 microg/l; thrombomodulin 3.94+/-1.81 vs. 3.94+/-1.51 microg/l; p=NS comparing post-placebo with post-folate). No correlation was observed between improvement in flow-mediated dilatation and change in endothelial marker proteins.']
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['Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis have been proposed as markers of ethanol intake. Because blood is not always available at autopsy, in this study we quantified FAEEs in human liver and adipose tissue as potential postmortem markers of premortem ethanol intake.', "Twenty-four sets of samples were collected at the Massachusetts State Medical Examiner's Office, and 7 sets of samples were obtained from the Pathology Department of Massachusetts General Hospital. Samples of liver and adipose tissue were collected at autopsy, and FAEEs were isolated and quantified from these organs as mass per gram of wet weight. Postmortem analysis of blood involved assessment for ethanol and other drugs.", 'The study shows a substantial difference in FAEE concentrations in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. In addition, a specific FAEE, ethyl arachidonate, was found at concentrations >200 pmol/g almost exclusively in the liver and adipose tissue of individuals with detectable blood ethanol at the time of death, providing an additional FAEE-related marker for prior ethanol intake.']
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['Valid tissue sampling of colorectal adenomas is crucial for their management in terms of treatment and follow-up. The aim of this study was to assess the validity of a cold biopsy sample as representative for the whole polypectomy specimen, with regard to histopathological features.', 'As part of the Norwegian Colorectal Cancer Prevention trial, 442 participants (60% men) who fulfilled the criterion of colonoscopic recovery of adenoma that had been biopsied at flexible sigmoidoscopy, had their adenomas subsequently removed by polypectomy (snare resection) at colonoscopy. Logistic regression analysis was used to determine which variables contributed to the histopathological discrepancy between cold biopsy and polypectomy specimens.', 'Among the 532 colorectal adenomas biopsied at flexible sigmoidoscopy and removed by colonoscopy, the assessment of intraepithelial neoplasia (dysplasia) status was changed in 51 adenomas (10%), and 38 (7%) of them had been underestimated at biopsy compared with polypectomy. Likewise, the assessment of villousness was changed in 45 adenomas (9%), being upgraded in 26 (6%) at polypectomy compared with biopsy. In a multivariate model, the diameter of neoplasia at polypectomy was positively associated with increased risk of the underestimation of intraepithelial neoplasia and/or villousness influencing a diagnosis of advanced colorectal neoplasia, when cold biopsy and polypectomy specimens were compared ( Ptrend=0.01). Among 56 cases of advanced neoplasia, 35 (63%) showed only low-grade intraepithelial neoplasia on biopsy.']
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['In transplantation, the antigen presentation step of T cell activation determines whether the T cell rejects the graft, ignores the graft, or inhibits other T cells from attacking the graft. Dendritic cells (DCs) are the most potent antigen presenting cells that are capable of activating naïve T cells. The purpose of the present study was to investigate the influence of anti-CD(45)RB monoclonal antibody on the phenotypes and functions of DCs and to further illustrate the mechanism of anti-CD(45)RB monoclonal antibody-inducing immunologic tolerance.', 'DCs from mice were cultured and treated with varying doses of anti-CD(45)RB monoclonal antibody at specific time points. Fluorescence-activated cell sorting (FACS) was used to verify the changes of phenotypes in the cultured DCs labeled with fluorescent antibody. DCs were also used as stimulators in mixed leukocyte reaction to detect their ability to stimulate T cell proliferation.', 'Anti-CD(45)RB monoclonal antibody induced a dose- and time-dependent suppression of maturation of DCs and a dose-dependent suppression of T cell proliferation in mixed leukocyte reaction when anti-CD(45)RB monoclonal antibody-treated DCs were used as stimulators.']
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['This study evaluated the capacity of dietary catechin (C), quercetin (Q), and the combination of both (CQ), to attenuate adipose inflammation triggered by high fructose (HFr) consumption in rats and by tumor necrosis factor alpha (TNF-α) in 3T3-L1 adipocytes.', 'In rats, HFr consumption for 6 wk caused dyslipidemia, insulin resistance, reduced plasma adiponectin, adiposity, and adipose tissue inflammation. Dietary supplementation with 20 mg/kg/day of C, Q, and CQ improved all these parameters. In 3T3-L1 adipocytes, C and Q attenuated TNF-α-induced elevated protein carbonyls, increased proinflammatory cytokine expression (MCP-1, resistin), and decreased adiponectin. The protective effects of C and Q on adipose inflammation are in part associated with their capacity to (i) decrease the activation of the mitogen-activated kinases (MAPKs) JNK and p38; and (ii) prevent the downregulation of PPAR-γ. In summary, C and Q, and to a larger extent the combination of both, attenuated adipose proinflammatory signaling cascades and regulated the balance of molecules that improve (adiponectin) or impair (TNF-α, MCP-1, resistin) insulin sensitivity.']
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['Meta-analyses link childhood trauma to depression, mania, anxiety disorders, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life.', 'We used data from a representative general population sample (NEMESIS-2, n\xa0=\xa06646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP, n\xa0=\xa0825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture.', 'In NEMESIS-2, largely comparable associations were found between childhood trauma and depression, mania, anxiety and psychosis. However, childhood trauma was considerably more strongly associated with their lifetime admixture. These results were confirmed in the patient samples, in which it was consistently found that patients with a history of childhood trauma were more likely to have a combination of multiple symptom domains compared to their non-traumatized counterparts. This pattern was also found in exposed individuals who did not meet criteria for a psychotic, affective or anxiety disorder and who did not seek help for subclinical psychopathology.']
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['Non-alcoholic fatty liver disease is an obesity-related chronic liver disorder ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis.', 'Tto investigate the role of Toll-like receptor (TLR) 4 in mediating the transition from steatosis to inflammation.', 'ApoE(-/-)/TLR4(mut) mice and ApoE(-/-)/TLR4 wild-type mice (ApoE(-/-)/TLR4-WT) were generated by cross-breeding an ApoE-deficient (ApoE(-/-)) strain with TLR4-mutant (TLR4(mut)) mice, which were fed with high-fat, high-cholesterol (HFHC) diet to induce obesity.', 'ApoE(-/-)/TLR4-WT mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH, which is associated with obesity and the metabolic syndrome. By contrast, ApoE(-/-)/TLR4(mut) mice lacking functional TLR4 were resistant to HFHC diet-induced liver inflammation and injury and were less susceptible to the diet-induced production of reactive oxygen species (ROS) and proinflammatory cytokines. In ApoE(-/-)/TLR4-WT mice, X-box binding protein-1 (XBP-1), a transcription factor involved in the unfolded protein responses, was activated in the liver by an HFHC diet, whereas XBP-1 activation was abrogated in ApoE(-/-)/TLR4(mut) mice. In primary rat Kupffer cells, endotoxin induced XBP-1 activation through ROS production, whereas siRNA-mediated knockdown of XBP-1 expression resulted in a marked attenuation in endotoxin-evoked NF-κB activation and cytokine production. Furthermore, adenovirus-mediated expression of dominant negative XBP-1 led to a significant attenuation in HFHC diet-induced liver inflammation and injury in mice.']
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['Understanding the series of morphogenetic processes that underlie the making of embryo structures is a highly topical issue in developmental biology, essential for interpreting the massive molecular data currently available. In mouse embryo, long-term in vivo analysis of cell behaviours and movements is difficult because of the development in utero and the impossibility of long-term culture.', 'We improved and combined two genetic methods of clonal analysis that together make practicable large-scale production of labelled clones. Using these methods we performed a clonal analysis of surface ectoderm (SE), a poorly understood structure, for a period that includes gastrulation and the establishment of the body plan. We show that SE formation starts with the definition at early gastrulation of a pool of founder cells that is already dorso-ventrally organized. This pool is then regionalized antero-posteriorly into three pools giving rise to head, trunk and tail. Each pool uses its own combination of cell rearrangements and mode of proliferation for elongation, despite a common clonal strategy that consists in disposing along the antero-posterior axis precursors of dorso-ventrally-oriented stripes of cells.']
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['Chronic inflammation and oxidative stress are key features of chronic obstructive pulmonary disease (COPD). Oxidative stress enhances COPD inflammation under the control of the pro-inflammatory redox-sensitive transcription factor nuclear factor-kappaB (NF-κB). Histone acetylation plays a critical role in chronic inflammation and bromodomain and extra terminal (BET) proteins act as "readers" of acetylated histones. Therefore, we examined the role of BET proteins in particular Brd2 and Brd4 and their inhibitors (JQ1 and PFI-1) in oxidative stress- enhanced inflammation in human bronchial epithelial cells.', 'Human primary epithelial (NHBE) cells and BEAS-2B cell lines were stimulated with IL-1β (inflammatory stimulus) in the presence or absence of H2O2 (oxidative stress) and the effect of pre-treatment with bromodomain inhibitors (JQ1 and PFI-1) was investigated. Pro-inflammatory mediators (CXCL8 and IL-6) were measured by ELISA and transcripts by RT-PCR. H3 and H4 acetylation and recruitment of p65 and Brd4 to the native IL-8 and IL-6 promoters was investigated using chromatin immunoprecipitation (ChIP). The impact of Brd2 and Brd4 siRNA knockdown on inflammatory mediators was also investigated.', 'H2O2 enhanced IL1β-induced IL-6 and CXCL8 expression in NHBE and BEAS-2B cells whereas H2O2 alone did not have any affect. H3 acetylation at the IL-6 and IL-8 promoters was associated with recruitment of p65 and Brd4 proteins. Although p65 acetylation was increased this was not directly targeted by Brd4. The BET inhibitors JQ1 and PFI-1 significantly reduced IL-6 and CXCL8 expression whereas no effect was seen with the inactive enantiomer JQ1(-). Brd4, but not Brd2, knockdown markedly reduced IL-6 and CXCL8 release. JQ1 also inhibited p65 and Brd4 recruitment to the IL-6 and IL-8 promoters.']
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['The treatment of long-gap esophageal atresia remains an issue for pediatric surgeons. Many techniques for treating long-gap esophageal atresia have been proposed, but the optimal method has not been established. The thoracoscopic esophageal elongation technique has recently been developed. We previously reported a case in which two-stage thoracoscopic repair was performed using internal esophageal traction without esophageal tearing, and we retrospectively reviewed the outcomes of this procedure in this study.', 'Five patients underwent thoracoscopic treatment involving internal esophageal traction for esophageal atresia involving a long gap or vascular ring over a 5-year period.', 'Between November 2010 and November 2015, 5 patients were treated with thoracoscopic traction. All of these patients successfully underwent thoracoscopic-delayed primary anastomosis. Conversion to open thoracotomy was not required in any case. The postoperative complications experienced by the patients included minor anastomotic leakage in 2 cases, anastomotic stenosis in 1 case, gastroesophageal reflux (GER) in 4 cases, and a hiatal hernia in 1 case. None of the patients died.']
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['The activity of neurogenic differentiation 1 (Neurod1) decreases after morphine administration, which leads to impairments of the stability of dendritic spines in primary hippocampal neurons, adult neurogenesis in mouse hippocampi, and drug-associated contextual memory. The current study examined whether Neurod1 could affect the development of opioid tolerance.', 'Lentivirus encoding Neurod1, microRNA-190 (miR-190), or short hairpin RNA against Neurod1 was injected into mouse hippocampi separately or combined (more than eight mice for each treatment) to modulate NeuroD1 activity. The antinociceptive median effective dose values of morphine and fentanyl were determined with tail-flick assay and used to calculate development of tolerance. Contextual learning and memory were assayed using the Morris water maze.', 'Decrease in NeuroD1 activity increased the initial antinociceptive median effective dose values of both morphine and fentanyl, which was reversed by restoring NeuroD1 activity. In contrast, decrease in NeuroD1 activity inhibited development of tolerance in a time-dependent manner, paralleling its effects on the acquisition and extinction of contextual memory. In addition, only development of tolerance, but not antinociceptive median effective dose values, was modulated by the expression of miR-190 and Neurod1 driven by Nestin promoter.']
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['Cholecystectomy is the therapy of first choice in patients with uncomplicated symptomatic cholecystolithiasis, but it remains unclear which patients truly benefit in terms of health status improvement. Patients generally present with episodic abdominal pain of varying frequency, duration, and intensity. We assessed whether characteristics of abdominal pain episodes are determinants of clinically relevant improvement of health status after cholecystectomy.', 'In a post hoc analysis of a prospective multicenter cohort study, patients of ≥18\xa0years of age with uncomplicated symptomatic cholecystolithiasis subjected to cholecystectomy were included. Preoperatively, patients received a structured interview and a questionnaire consisting of the visual analogue scale (VAS; range 0-100) and gastrointestinal quality of life index (GIQLI). At 12\xa0weeks after cholecystectomy, the GIQLI was again administered. Logistic regression analyses were performed to determine significant associations.', 'Questionnaires were sent to 261 and returned by 166 (63.6\xa0%) patients (128 females, mean age at surgery 49.5\u2009±\u200913.8). A total of 131 (78.9\xa0%) patients reported a clinically relevant improvement of health status. The median (interquartile range) frequency, duration, and intensity of abdominal pain episodes were 0.38 (0.18-0.75) a week, 4.00 (2.00-8.00) hours, and 92 (77-99), respectively. None of the characteristics was associated with a clinically relevant improvement of health status at 12\xa0weeks after cholecystectomy.']
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['The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml.', 'A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.).', 'The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml.']
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['British society is multicultural and multilingual, thus for many children English is not their main or only language. Speech and language therapists are required to assess accurately the speech and language skills of bilingual children if they are suspected of having a disorder. Cultural and linguistic diversity means that a more complex assessment procedure is needed and research suggests that bilingual children are at risk of misdiagnosis. Clinicians have identified a lack of suitable assessment instruments for use with this client group.', 'This paper highlights the challenges of assessing bilingual children and reviews available speech and language assessment procedures and approaches for use with this client group. It evaluates different approaches for assessing bilingual children to identify approaches that may be more appropriate for carrying out assessments effectively.', 'This review discusses and evaluates the efficacy of norm-referenced standardized measures, criterion-referenced measures, language-processing measures, dynamic assessment and a sociocultural approach.', 'When all named procedures and approaches are compared, the sociocultural approach appears to hold the most promise for accurate assessment of bilingual children. Research suggests that language-processing measures are not effective indicators for identifying speech and language disorders in bilingual children, but further research is warranted. The sociocultural approach encompasses some of the other approaches discussed, including norm-referenced measures, criterion-referenced measures and dynamic assessment.']
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['Successful pregnancies require fine tuning of fibrinolytic activities in order to secure fibrin polymerization and stabilization of the placental basal plate as well as to prevent excess fibrin deposition in placental vessels and intervillous spaces. Fibrinolysis is tightly regulated by plasminogen activator inhibitor-1 (PAI-1). Endothelial PAI-1 synthesis is induced by angiotensin II, which is generated by angiotensin I-converting enzyme (ACE).', 'We studied the ACE deletion (D)/insertion (I) polymorphism and the PAI-1 4G/5G polymorphism in women with recurrent spontaneous miscarriages (RM). Both polymorphisms have been shown to be associated with ACE and PAI-1 expression levels respectively. A study group of 184 patients with a history of two or more consecutive unexplained spontaneous miscarriages was compared with a control group of 127 patients with uneventful term deliveries and no history of miscarriages.', 'Our findings show: (i) homozygosity for the D allele of the ACE gene, which results in elevated PAI-1 concentrations and hypofibrinolysis, is associated with an elevated risk of RM; (ii) the combination of the D/D genotype with two 4G alleles of the PAI-1 promoter, which further increases PAI-1 plasma levels, is significantly more frequent in RM patients compared with controls.']
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['Surgical wound classification (SWC) is a component of surgical site infection risk stratification. Studies have demonstrated that SWC is often incorrectly documented. This study examines the accuracy of SWC after implementation of a multifaceted plan targeted at accurate documentation.', 'A reviewer examined operative notes of 8 pediatric operations and determined SWC for each case. This SWC was compared with nurse-documented SWC. Percent agreement pre- and postintervention was compared. Analysis was performed using chi-square and a P value less than .05 was significant.', 'Preintervention concordance was 58% (112/191) and postintervention was 83% (163/199, P = .001). Appendectomy accuracy was 28% and increased to 80% (P = .0005). Fundoplication accuracy increased from 44% to 84% (P = .016) and gastrostomy tube from 56% to 100% (P = .0002). The most accurate operation preintervention was pyloromyotomy and postintervention was gastrostomy tube and inguinal hernia. The least accurate pre- and postintervention was cholecystectomy.']
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['Studies have shown that the addition of right precordial and left posterior leads to the standard 12-lead electrocardiogram (ECG) can significantly improve the sensitivity of exercise treadmill testing (ETT) for the diagnosis of myocardial ischemia.', 'The objective of this study was to determine the value of adding 2 rightsided (RV3, RV4) and 2 left posterior (V8, V9) auxiliary leads to enhance detection of myocardial ischemia in patients with chest pain identified as low risk.', 'The authors conducted a prospective study of all patients undergoing ETT as part of their management in a chest pain evaluation unit (CPEU) at a tertiary medical center from November 1999 to November 2001. Patients were considered low risk for acute coronary syndrome based on the clinical presentation to the CPEU, absence of ischemia on resting ECG, and negative initial cardiac markers. Diagnosis of coronary artery disease (CAD) was based on confirmatory testing, which included coronary angiography, myocardial stress scintigraphy, exercise echocardiography, or 30-day follow-up period.', 'The study cohort comprised 705 patients who underwent 16-lead ETT. Of these, 70 (10%) had positive ETT and CAD was confirmed by further evaluation in 26. ECG changes positive for ischemia were demonstrated on the standard 12-lead exercise ECG in 68 patients. An additional 2 patients had positive ECG alterations only in the 4 auxiliary leads on the 16-lead ECG. There was no significant difference in the sensitivity or positive predictive value between the 12- and 16-lead exercise ECG.']
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['Transplant nephrectomy has been reported to display a high morbidity (17% to 56%) and considerable mortality (13% to 14%). We used a debulking technique leaving an intact ureter with intracapsular instillation of betadine; it was associated with a low rate of complications.', 'A total of 25 patients (16 males, 9 females) with failed allografted kidneys underwent transplant nephrectomy between 1991 and 2006 (Group 1). All subjects had failed kidneys for 2 months or more posttransplantation. The surgical approach to allograft nephrectomy was via the same oblique incision in the iliac fossa as the original transplantation. The capsule of the allograft was exposed and incised from pole to pole for the renal parenchyma to be bluntly dissected free with an index finger. The kidney parenchyma was pulled outward, and then the pedicle was ligated with silk, and layer by layer the tissue was removed until reaching the pedicle. Again it was transfixed and carefully ligated. After homeostasis, diluted betadine was instilled into the capsule and a drain inserted. The allograft ureter and capsule were left intact. All cases were followed for at least 1 year. Postnephrectomy, small doses of immunosuppressive drugs were continued for at least 2 months.', 'Intracapsular nephrectomy was not associated with a significant complication.']
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['Hind limb ischemia-reperfusion (I/R) injury increases gut permeability, and resultant endotoxemia is associated with an amplified systemic inflammatory response syndrome leading to multiple organ dysfunction syndrome. We studied the potential role of recombinant bactericidal/permeability-increasing protein (rBPI(21) ), a novel antiendotoxin therapy, in modulating endotoxin-enhanced systemic inflammatory response syndrome in hind limb I/R injury.', 'In this prospective, randomized, controlled, experimental animal study, 48 male Wistar rats, weighing 300 to 350 g, were randomized to a control group (sham) and five groups undergoing 3 hours bilateral hind limb ischemia with 2 hours reperfusion (I/R) (n = 8 per group). The control and untreated I/R groups received thaumatin, a control-protein preparation, at 2 mg/kg. Treatment groups were administered rBPI(21) intravenously at 1, 2, or 4 mg/kg body weight at the beginning of reperfusion; an additional group was administered rBPI(21) intravenously at 2 mg/kg after 1 hour of reperfusion. Plasma interleukin-6 concentration was estimated by bioassay as a measure of systemic inflammation. Plasma endotoxin concentration was determined by use of an amebocyte lysate chromogenic assay. Crossreactive immunoglobulin G and M antibodies to the highly conserved inner core region of endotoxin were measured by use of an enzyme-linked immunosorbent assay. The lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively.', 'I/R provoked highly significant elevation in plasma interleukin-6 concentrations (1351.20 pg/mL [860.16 - 1886.40 pg/mL]) compared with controls (125.32 pg/mL [87.76-157.52 pg/mL; P <.0001]), but treatment with rBPI(21) 2 mg/kg at onset of reperfusion (715.89 pg/mL [573.36-847.76 pg/mL]) significantly decreased interleukin-6 response compared with the nontreatment group ( P <.016). I/R increased plasma endotoxin concentrations significantly (21.52 pg/mL [6.20-48.23 pg/mL]), compared with control animals (0.90 pg/mL [0.00-2.30 pg/mL; P <.0001]), and treatment with rBPI(21) 4 mg/kg at reperfusion significantly decreased endotoxemia (1.30 pg/mL [1.20-2.20 pg/mL]), compared with the untreated group ( P <.001). The lung tissue myeloperoxidase level was significantly increased in the untreated I/R group (208.18% [128.79%-221.81%]), compared with in controls (62.00% [40.45%-80.92%; P <.0001]), and attenuated in those treated with rBPI(21) 2 mg/kg (129.54% [90.49%-145.78%; P <.05]). Data represent median and interquartile range, comparisons made with the nonparametric Mann-Whitney U test.']
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