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['Platelets play an important role in the natural history of coronary artery disease. Enhanced platelet aggregation and receptor expression unquestionably occur after coronary stent implantation; however, the functional characteristics of platelets before stenting have not been fully elucidated.', 'Platelets were assessed before intervention by platelet-rich plasma aggregation (PA) with 5 mmol adenosine diphosphate (ADP) and 1 mg/mL collagen; whole blood aggregation (WBA) by 1 mg/mL collagen; shear-induced closure time (CT); contractile force (CF); and expression of 9 surface receptors by flow cytometry in 126 patients undergoing elective coronary artery stent placement. All patients received aspirin for at least 7 days. The data were compared with those from 64 healthy volunteers.', 'Each test revealed sustained platelet activation in patients undergoing coronary stenting compared with control values. These differences were significant for collagen-induced PA (P =.031); CF (P =.0001); expression of glycoprotein (GP) IIb/IIIa (P =.0001); P-selectin (P =.0008); platelet/endothelial cell adhesion molecule (PECAM)-1 (P =.0001); CD107a (P =.0001); CD107b (P =.0004); and CD63 (P =.009).']
['To investigate the hypothesis that the stimulation of pyruvate oxidation by dichloroacetate (DCA) administration would increase the level of intramuscular glutamine in severely burned patients.', 'The level of intramuscular glutamine decreases in response to severe injury, and the rate of intramuscular glycolysis and pyruvate oxidation is elevated. Intramuscular glutamine concentrations have been correlated to muscle protein synthesis.', 'Six studies were conducted on five patients with burns >40% total body surface area. Patients were studied in the fed state during an 8-hour stable isotope infusion. After 5 hours, DCA (30 mg/kg) was administered for 30 minutes.', 'Analysis of muscle biopsy samples taken at 5 and 8 hours of the study revealed a 32% increase in intracellular glutamine levels after DCA administration. Increased intracellular glutamine concentrations did not affect skeletal muscle protein synthesis as determined by a three-pool arteriovenous model or by the direct incorporation of isotope into skeletal muscle protein. DCA administration resulted in a decrease in plasma lactate but no change in alanine de novo synthesis or intracellular concentration.']
['Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. Although both dimethylarginines may be important regulators of the arginine-NO pathway, their metabolism is largely unknown. Both dimethylarginines are removed from the body by urinary excretion. However, ADMA is also subject to enzymatic degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. To elucidate the role of the liver in the metabolism of ADMA, we aimed to investigate dimethylarginine handling of the liver in detail.', 'Ten male Wistar rats were used for this study. Blood flow was measured using radiolabeled microspheres according to the reference sample method. Concentrations of dimethylarginines were measured by HPLC. The combination of arteriovenous concentration difference and organ blood flow allowed calculation of net organ fluxes and fractional extraction rates.', 'Both the liver (0.89+/-0.11) and the kidney (0.68+/-0.06) showed a high net uptake (nmol/100 g body weight (BW)/min) of ADMA, whereas a significant net uptake of SDMA was only observed in the kidney (0.34+/-0.04). For the liver, fractional extraction rates were 29.5% +/-3.0 for ADMA and 0.0%+/-3.7 for SDMA. Fractional extraction rates of ADMA and SDMA for the kidney were 36.0%+/-2.7 and 31.6%+/-3.8, respectively.']
['The relationship between plasma level of total homocysteine (tHcy) and white matter hyperintensities (WMHs), especially in patients with acute ischemic stroke (AIS), is controversial. The present study investigated the association between these two as well as WMH locations in a large cohort of patients with AIS.', 'Consecutive patients were reviewed from a prospective ischemic stroke database. Clinical data, including tHcy level and WMHs, were assessed. WMHs were assessed using the Fazekas scale and Age-Related White Matter Changes (ARWMC) visual grading scale. The association between tHcy and WMH locations was investigated by using multivariate logistic regression analyses.', 'A total of 923 out of 1,205 patients were examined. The average age was 58.9 ± 11.9 years; 31.6% were female. Elevated tHcy level was significantly associated with WMHs. For the highest tHcy quartile, the odds ratio (OR) (95% confidence interval; CI) was 1.891 (1.257; 2.843) according to the Fazekas scale and 1.781 (1.185; 2.767) according to the ARWMC scale when compared to the lowest quartile. However, in a subgroup analysis, only WMHs in the periventricular area and left or right frontal areas were found to be independently associated with tHcy level. For the highest tHcy quartile, the OR (95% CI) was 1.761 (1.172; 2.648) for the periventricular WMHs, 1.768 (1.134; 2.756)for the left frontal WMHs, and 1.890 (1.206; 2.960)for the right frontal WMHs.']
['45S5 bioglass mixed with 50% phosphoric acid has been suggested to treat dentine hypersensitivity and incipient enamel caries. This study is going to evaluate the biocompatibility of using the aforementioned technique with the rat pulpal cells.', 'The relative cytotoxicity of 45S5 bioglass on rat dental pulp cells was compared to the cytotoxicity of a temporary filling material (Caviton; GC, Japan), Type 1 glass ionomer cement (Fuji I; GC, Tokyo, Japan) and commercial desensitising agent (SuperSeal; Phoenix Dental, Fenton, MI, USA) using a transwell insert model. Cell viability was measured by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The number of viable cell counts were compared using one way ANOVA (p<0.05). The morphological alterations of the pulp cells were observed directly by phase contrast microscope.', 'The results of this study indicated that cell viability recorded by the 45S5 bioglass paste group did not differ significantly from those of the Caviton, glass ionomer or superseal, moreover pulpal cells microscopic analysis revealed that 45S5 bioglass elicited minimal toxic effect.']
["The activation of cannabinoid receptor 2 (CB2) has the beneficial effect of reducing neuroinflammatory response in the treatment of Alzheimer's disease (AD) and is suggested to trigger the peroxisome proliferator-activated receptor-γ (PPARγ) pathway; agonists of both receptors improve AD. Recently, the plant metabolite β-caryophyllene was shown to selectively bind to CB2 receptor and act as a full agonist.", 'In this study, we examined the anti-inflammatory effect of β-caryophyllene in a transgenic APP/PS1 AD model and analyzed whether this effect was mediated by CB2 and PPARγ.', 'β-Caryophyllene, given orally, prevented cognitive impairment in APP/PS1 mice, and this positive cognitive effect was associated with reduced β-amyloid burden in both the hippocampus and the cerebral cortex. Moreover, β-caryophyllene reduced astrogliosis and microglial activation as well as the levels of COX-2 protein and the mRNA levels of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the cerebral cortex. The use of the CB2 antagonist AM630 or the PPARγ antagonist GW9662 significantly reversed the protective effects of β-caryophyllene on APP/PS1 mice.']
['Sonic hedgehog (Shh) signal transduction involves the ligand binding Patched1 (Ptc1) protein and a signaling component, Smoothened (Smo). A select group of compounds inhibits both Shh signaling, regulated by Ptc1, and late endosomal lipid sorting, regulated by the Ptc-related Niemann-Pick C1 (NPC1) protein. This suggests that Ptc1 regulates Smo activity through a common late endosomal sorting pathway also utilized by NPC1. During signaling, Ptc accumulates in endosomal compartments, but it is unclear if Smo follows Ptc into the endocytic pathway.', 'We characterized the dynamic subcellular distributions of Ptc1, Smo, and activated Smo mutants individually and in combination. Ptc1 and Smo colocalize extensively in the absence of ligand and are internalized together after ligand binding, but Smo becomes segregated from Ptc1/Shh complexes destined for lysosomal degradation. In contrast, activated Smo mutants do not colocalize with nor are cotransported with Ptc1. Agents that block late endosomal transport and protein sorting inhibit the ligand-induced segregation of Ptc1 and Smo. We show that, like NPC1-regulated lipid sorting, Shh signal transduction is blocked by antibodies that specifically disrupt the internal membranes of late endosomes, which provide a platform for protein and lipid sorting.']
['Previous studies have demonstrated that fibronectin (FN) levels are increased in brain tissues from patients and animals with epilepsy. This study aimed to assess FN levels in cerebrospinal fluid (CSF) and serum samples from patients with epilepsy.', 'Fibronectin levels were assessed in CSF and serum samples from 56 patients with epilepsy (27 and 29 individuals with intractable epilepsy and nonintractable epilepsy, respectively) and 25 healthy controls, using sandwich enzyme-linked immunosorbent assays (ELISA).', 'CSF-FN levels were higher in patients with epilepsy (8.07 ± 1.51 mg/l versus 6.20 ± 1.18 mg/l, p<0.05) than in the control group. In addition, serum-FN levels in the group with epilepsy and in the control group were 236.96 ± 65.7 mg/l and 181.43 ± 72.82 mg/l, respectively, indicating a statistically significant difference (p=0.01). Interestingly, serum- and CSF-FN levels in individuals with epilepsy were not affected by antiepileptic drug and duration of epilepsy. Of note, the increase of CSF- and serum-FN levels was more pronounced in subjects with intractable epilepsy than in patients with nonintractable epilepsy.']
['Increased adipose thermogenesis is being considered as a strategy aimed at preventing or reversing obesity. Thus, regulation of the uncoupling protein 1 (UCP1) gene in human adipocytes is of significant interest. Retinoic acid (RA), the carboxylic acid form of vitamin A, displays agonist activity toward several nuclear hormone receptors, including RA receptors (RARs) and peroxisome proliferator-activated receptor δ (PPARδ). Moreover, RA is a potent positive regulator of UCP1 expression in mouse adipocytes.', 'The effects of all-trans RA (ATRA) on UCP1 gene expression in models of mouse and human adipocyte differentiation were investigated. ATRA induced UCP1 expression in all mouse white and brown adipocytes, but inhibited or had no effect on UCP1 expression in human adipocyte cell lines and primary human white adipocytes. Experiments with various RAR agonists and a RAR antagonist in mouse cells demonstrated that the stimulatory effect of ATRA on UCP1 gene expression was indeed mediated by RARs. Consistently, a PPARδ agonist was without effect. Moreover, the ATRA-mediated induction of UCP1 expression in mouse adipocytes was independent of PPARγ coactivator-1α.']
['Although it is known that the chemokines CXCL12 and CCL20 are expressed in the intestine, their contribution to lymphocyte homing has not been investigated in detail. The authors investigated whether the CXCL12-CXCR4 and CCL20-CCR6 systems are involved in T lymphocyte-endothelial interaction in microvessels of the small and large intestines.', 'Labeled lamina proprial lymphocytes (LPLs) were administered to mice, and their adhesion to microvessels of normal and TNF-alpha -induced inflamed intestinal mucosa was observed under an intravital microscope. Antibodies against CXCL12, CCL-20, or CCL-25 were administered prior to lymphocyte administration, and in some experiments CXCR4 or CCR6 on LPLs was desensitized with an excess amount of chemokine.', 'LPLs adhered to microvessels of the ileum and colon, and TNF-alpha induced a significant accumulation at both sites. Blocking of the CXCL12-CXCR4 system significantly inhibited the LPL adhesion in the ileum and colon under both normal and TNF-alpha -treated conditions. However, blocking of the CCL20-CCR6 system significantly attenuated LPL adhesion only under a TNF-alpha -treated condition. There was an additive inhibitory effect on LPL adherence by CXCL12 and CCL20 blocking in TNF-alpha -induced inflamed intestines. There was also an additive function of the CCL25-CCR9 system in LPL accumulation in the small intestine.']
["It is known that different autoimmune diseases often share the same susceptibility genes. In this study we aimed to investigate if loci found associated with common autoimmune diseases in recent genome-wide association studies also could be susceptibility loci for autoimmune Addison's disease (primary adrenal insufficiency).", "A total of 139 tagging single nucleotide polymorphisms (SNPs) in 11 candidate genes (IL2, IL21, IL2RA, CLEC2D, CD69, ERBB3, PTPN11, SH2B3, CLEC16A, CIITA, and PTPN2) were genotyped in a case/control study design consisting of Norwegian Addison's disease patients (n = 332) and Norwegian healthy control individuals (n = 1029). Five SNPs were subsequently selected for analysis in a United Kingdom sample set consisting of Addison's disease patients (n = 210) and controls (n = 191).", "Polymorphisms in CLEC16A and CIITA remained significantly associated with Addison's disease in the Norwegian sample set at the 0.05 level, even after correction for multiple testing. CLEC16A and CIITA are both located at 16p13, but linkage disequilibrium patterns and logistical regression analyses suggest that SNPs in these two genes are independently associated with Addison's disease. We were not able to confirm these associations in the United Kingdom material, however, this may well be due to the limited sample size and lack of statistical power."]
['To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes.', 'A cohort of 2250 women, 34-54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status.', 'Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status.']
['Traumatic injury of the optic nerve leads to retrograde cell death of retinal ganglion cells (RGCs) but usually a certain percentage of neurons survive. It has been suggested that recovery of axonal transport is beneficial for survival. The present study was therefore performed to provide a synopsis of the temporal pattern of axonal transport decline/recovery and the viability of RGCs after optic nerve crush (ONC).', 'Fluorescent dyes were injected into the superior colliculus to retrogradely label RGCs. Axonal transport kinetics into the RGCs was visualized with in vivo confocal neuroimaging (ICON) in uninjured rats and in rats which had mild or moderate ONC. Red fluorescent beads were injected on day 2 post-ONC and green beads on day 7.', 'At 2 to 4 days post-ONC significant axonal transport was detected, but within 1 week the transport of the fluorescent beads was decreased. Interestingly, during post-ONC week 3 the axon transport slowly recovered. However, despite this recovery, retrograde cell death rate continued and was even increased in a "second wave" of cell death in those neurons that displayed axon transport recovery.']
['Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing.', 'We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were determined at baseline and after 5 years. Pulmonary vein flow pattern assessment and septal myocardial Doppler imaging were additionally performed at follow-up.', 'At follow-up, BP was not significantly different between the two groups (128 +/- 11/84 +/- 10 v 123 +/- 11/81 +/- 5 mm Hg, OHyp v ONorm) but five OHyp had developed mild hypertension. LV mass index remained unchanged and was not different between the two groups at follow-up (92 +/- 17 v 92 +/- 14 g/m2). Diastolic echocardiographic properties were similar at baseline, but, at follow-up, the following differences were found: mitral E deceleration time (209 +/- 32 v 185 +/- 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 +/- 15 v 107 +/- 12 msec, P < .05) were prolonged in the OHyp as compared to the ONorm. Compared to the normotensive subjects, the five OHyp who developed hypertension had more pronounced alterations of LV diastolic function, that is, significantly higher mitral A (54 +/- 7 v 44 +/- 9 cm/sec, hypertensives v normotensives, P < .05), lower E/A ratio (1.31 +/- 0.14 v 1.82 +/- 0.48, P < .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 +/- 0.3 v 0.81 +/- 0.16, P < .005), longer myocardial isovolumic relaxation time (57 +/- 7 v 46 +/- 12 msec, P < .05) as well as smaller myocardial E (10 +/- 1 v 13 +/- 2 cm/sec, P < .05) and E/A ratio (1.29 +/- 0.25 v 1.78 +/- 0.43, P < .05), despite similar LV mass (91 +/- 16 v 93 +/- 18 g/m2).']
['To investigate the association between the level of serum brain-derived neurotrophic factor (sBDNF) and the therapeutic efficacy of modified electroconvulsive therapy (MECT) in Chinese patients with depressive disorder.', 'Twenty-eight patients with depressive episode and 28 healthy subjects were recruited in the current study. The sBDNF level was examined in all subjects before treatment and after a 2-week treatment with MECT in patients with depression. The severity of depression was measured according to the 17-item Hamilton Rating Scale for Depression in patients with depression.', 'The severity of depression reduced significantly in patients with depression after a 2-week treatment with MECT (31.39 [SD, 4.65] vs 8.14 [5.52], P < 0.001). Serum BDNF level in patients with depression was significantly lower than that of the control group before treatment (5.66 [SD, 2.07] vs 9.17 [SD, 1.26] ng/mL, P < 0.001), then increased remarkably to the level of control subjects 2 weeks after MECT (7.90 [SD, 3.42] ng/mL). The increasing rate of sBDNF in patients with depression was significantly correlated with the decreasing rate of the total 17-item Hamilton Rating Scale for Depression score (r = 0.532, P = 0.004) and cluster scores of cognitive dysfunction (P = 0.018) and retardation (P = 0.048).']
['To evalueate hepatoprotective effects Feronia elephantum (F. elephantum) correa against thioacetamide (TA) induced liver necrosis in diabetic rats.', 'Male wistar rats were made diabetic with alloxan (160 mg/kg) on day 0 of the study. They were intoxicated with hepatotoxicant (thioacetamide, 300 mg/kg, ip) on day 9 of study to produce liver necrosis. Effects of 7 day daily once administration (day 2 to day 9) of EF (400 and 800 mg/kg, po) were evaluated on necorosis of liver in terms of mortality, liver volume, liver weight, serum aspartate aminotransferase (AST) and serum alanine transaminase (ALT), and histopathology of liver sections (for signs of necorosis and inflammation) on day-9 of the study. Separate groups of rats with treated only with alloxan (DA control), thioacetamide (TA control) and both (TA+DA control) were maintained.', 'FE significantly lowered the mortality rate and showed improvement in liver function parameters in TA-induced diabetic rats without change in liver weight, volume and serum glucose levels.']
['Treatment with angiotensin-converting enzyme (ACE) inhibitors affects the autoregulation of renal blood flow and glomerular filtration and provides renal protective effects. The purpose of this case-control study was to investigate the effects of chronic ACE inhibition on perioperative renal hemodynamics and function.', 'We prospectively studied renal function in two groups of patients, chronically treated or not, with ACE inhibitors (ACEI and control; n = 16, in each group) who underwent elective cardiac surgery under hypothermic cardiopulmonary bypass. Glomerular filtration rate, effective renal plasma flow, osmolar clearance and fractional excretion of sodium and potassium were determined before, during and after CPB. Additional measurements included plasma atrial natriuretic factor (ANF) as well as plasma and urinary cyclic GMP (cGMP), thromboxane B2 (TxB2) and 6-keto-PGF1.', 'Renal functional and hemodynamic variables did not differ between the two groups, at any period. Cardiopulmonary bypass induced increases in urinary flow, osmolar clearance and fractional excretion of sodium and potassium in both groups. Plasma and urinary ratio of 6-keto-PGF to TxB2 increased markedly and reflected a predominant systemic and renal release of vasodilatory prostaglandins. Intraoperatively, ANF was higher in ACEIs than in control patients.']
['Collagen-containing leukocytes (CD45+Col-I+) accumulate in diseased and fibrotic tissues. However, the precise identity of these cells and whether injury is required for their recruitment remain unknown. Using a murine model of pulmonary fibrosis in which an inducible, bioactive form of the human transforming growth factor (TGF)-β1 gene is targeted to the lung, we characterized the cell surface phenotype of collagen-containing CD45+ cells in the lung and tested the hypothesis that apoptotic cell death responses are essential to the accumulation of CD45+Col-I+ cells.', 'Our studies demonstrate that CD45+Col-I+ cells appearing in the TGF-β1-exposed murine lung express markers of the monocyte lineage. Inhibition of apoptosis via pharmacological caspase blockade led to a significant reduction in CD45+Col-I+ cells, which appear to accumulate independently of alternatively activated macrophages. There are also increased levels of apoptosis and greater numbers of CD45+Col-I+ in the lung tissue of patients with two distinct forms of fibrotic lung disease, idiopathic pulmonary fibrosis and connective tissue disease-related interstitial lung disease, when compared to lung from healthy normal controls. These findings are accompanied by an increase in collagen production in cultured monocytes obtained from subjects with fibrotic lung disease. Treatment of these cultured cells with the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD/fmk) reduces both apoptosis and collagen production in all subjects.']
['Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation.', 'Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification.', 'Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks.']
['Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET), is able to predict the long-term clinical outcome of aSAH.', 'The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and 1 week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI 1 year after SAH.', 'High RD2 (OR 1.96; 95% CI 1.18-3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78-24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1-4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome 1 year after aSAH.']
['Elevated expression levels of S100A6, a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies. Moreover, increased serum levels of S100A6 were suggested as a novel biomarker for various inflammatory and malignant diseases including lung and gastric cancer. However, up to now, serum concentrations of S100A6 have not been analyzed in patients with cholangiocarcinoma (CCA).', 'S100A6 mRNA expression levels were analyzed in human and murine CCA tumor samples, using semi-quantitative reverse transcriptase PCR. S100A6 serum concentrations were measured using an enzyme-linked immunosorbent assay in 112 patients with CCA referred to surgery for curative resection and were compared to those of 42 healthy controls. Results were correlated with clinical data.', 'S100A6 mRNA expression levels were significantly up-regulated in tumor samples of CCA patients and in tumor tissue of a CCA mouse model. In contrast, serum levels of S100A6 were not significantly altered in patients with CCA compared to healthy controls. Whereas no differences became apparent within the different clinical subgroups of CCA, patients with primary sclerosing cholangitis (PSC)-based CCA displayed higher levels of S100A6 compared to the other patients. Nevertheless, patients with higher S100A6 serum concentrations showed a trend towards an impaired prognosis compared to patients with lower levels. Finally, within our cohort of patients both the diagnostic and prognostic potentials of S100A6 were similar to those of the clinically established biomarkers CEA and CA19-9.']
['To determine whether lowering oxygen saturation alarm limits for infants at risk for retinopathy of prematurity (ROP) reduces its incidence and/or severity.', "Oximetry alarm limits were lowered to 85% and 93% for all infants with a birth weight 1250 g or less and/or gestational age 28 weeks or less, and maintained until 32 weeks' postmenstrual age or until oxygen saturations were consistently greater than 93% in room air. The new policy was effective for infants born on or after June 1, 2003. ROP data were prospectively collected, and we compared the rate and severity of ROP in the year after the oximeter alarm policy change to the rates in the immediately preceding 3 years.", 'In the year after the oximeter alarm limit policy change, 4 of 72 infants developed prethreshold ROP compared with 44 of 251 infants in the previous 3-year epoch (17.5% vs 5.6%, p=0.01). Similarly, only 6 of 144 eyes developed prethreshold ROP in the year after the policy change, compared with 84 of 502 in the previous 3 years (16.7% vs 4.2%, p=0.001).']
['Repetitive transcranial magnetic stimulation can be used to explore functional connectivity between cortical areas.', 'To determine the effects of two theta burst stimulation (TBS) patterns (intermittent, iTBS; and continuous, cTBS) of left dorsal premotor cortex (PMd).', 'Left PMd was identified in 11 participants using functional magnetic resonance imaging (fMRI), during performance of complex sequential finger movements. Each participant received iTBS, cTBS, or sham TBS of left PMd in three separate sessions within a randomized, single-blind design. The speed and accuracy of simple and complex sequential reaction time (RT) task performance was measured before and after TBS. The excitability of primary motor cortex (M1) bilaterally, and interhemispheric facilitation from left PMd to right M1, were also measured before and after TBS.', 'iTBS sped up the preparation of complex sequences performed with the right hand, with no detectable changes in M1 excitability. RT performance was maintained after cTBS, in the presence of increased left M1 excitability and suppressed right M1 excitability.']
['The distinction between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) is not always easy, so much so that the WHO 2008 Blue Book has incorporated a provisional category of "B-cell lymphoma, unclassifiable with features intermediate between DLBCL and BL." One of the immunohistochemical (IHC) markers used at times to differentiate between the two is IHC expression of BCL2, which was initially believed to be consistently negative in BL. Later it was recognized that weak BCL2 expression is still compatible with the diagnosis of BL. To verify or otherwise this current view this study was undertaken.', 'We retrieved 39 confirmed cases of BL, in both children and adults. All these cases had typical morphology, IHC profile, and Mib-1 index that are typical of BL. All these cases were then stained with a monoclonal antibody against BCL2 oncoprotein, using 2-step Envision system.', 'Out of 39 cases, 31 cases (79.4%) were completely negative for BCL2, whereas 5 (12.8%) were weak focal positive. However, another 4 (10.2%) cases did show strong diffuse cytoplasmic staining for BCL2. Fluorescent in-Situ hybridization (FISH) for t(14:18) was optimally done on 6 out of 9 cases. All these 4 cases were from adults with 3 out of 4 arising in the parotid region. Two out of 4 cases also showed t(8:14) on FISH.']
['An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking.', 'We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152).', 'MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development.']
['To achieve tunable pH-dependent drug release in tumor tissues.', 'Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h.', 'A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths.']
['To investigate the effect of angiotensin II (Ang II) in the hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion (IR) injury and to assay the role of renal sympathetic nerve activity (RSNA).', 'A cannula was inserted into the right side PVN in Sprague-Dawley rats for microinjection of Ang II (3, 30, and 300\xa0ng); Ang II AT1 receptor antagonist, losartan (0.3\xa0μg); and the superoxide dismutase (SOD) mimetic, tempol (20\xa0nmol) before right side nephrectomy. After 1\xa0wk, renal IR injury was induced by clamping the left renal artery for 45\xa0min, and then reperfusion for 3 or 24\xa0h. The extent of renal damage was determined by evaluation of renal functional indices. RSNA was recorded in all groups. Oxidative stress indices (SOD activity and malondialdehyde levels) were assayed in the PVN.', 'Microinjection of pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3\xa0ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished by pretreatment with tempol.']
['There is growing international concern that food insecurity may negatively impact antiretroviral (ARV) treatment outcomes, but no studies have directly evaluated the effect of food insecurity on viral load suppression and antiretroviral adherence. We hypothesized that food insecurity would be associated with poor virologic response among homeless and marginally housed HIV-positive ARV-treated patients.', 'This is a cross-sectional study.', 'Participants were ARV-treated homeless and marginally housed persons receiving adherence monitoring with unannounced pill counts in the Research on Access to Care in the Homeless (REACH) Cohort.', 'Food insecurity was measured by the Household Food Insecurity Access Scale (HFIAS). The primary outcome was suppression of HIV viral RNA to <50 copies/ml. We used multivariate logistic regression to assess whether food insecurity was associated with viral suppression.', 'Among 104 participants, 51% were food secure, 24% were mildly or moderately food insecure and 25% were severely food insecure. Severely food insecure participants were less likely to have adherence > or =80%. In adjusted analyses, severe food insecurity was associated with a 77% lower odds of viral suppression (95% CI = 0.06-0.82) when controlling for all covariates. In analyses stratified by adherence level, severe food insecurity was associated with an 85% lower odds of viral suppression (95% CI = 0.02-0.99) among those with < or =80% adherence and a 66% lower odds among those with >80% adherence (95% CI = 0.06-1.81).']
['PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.', 'A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.', 'No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25).']
['Retinoic acid is necessary for the growth and differentiation of organisms and exerts its molecular actions by binding to specific nuclear receptors that belong to the thyroid-steroid hormone receptor superfamily. Steroids and retinoids control the differentiation of the female reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia.', 'Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival.', 'We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 microg retinoic acid/g diet. Mice were either ovariectomized or intact. Squamous cells arising in the normally simple columnar epithelium of the endocervix and uterine cavity were monitored by keratin 5 expression with immunohistochemistry.', 'Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%.']
['The first derivative of left ventricular (LV) pressure over time (dP/dt max) is a marker of LV systolic function that can be assessed during cardiac catheterization and echocardiography. Radial artery dP/dt max has been proposed as a possible marker of LV systolic function and we sought to test this hypothesis.', 'We compared simultaneously recorded radial dP/dt max (by high-fidelity tonometry) with LV dP/dt max (by high-fidelity catheter and echocardiography parameters analogous to LV dP/dt max). In study 1, beat-to-beat radial dP/dt max and LV dP/dt max were recorded at rest and during supine exercise in 12 males (aged 61 +/- 12 years) undergoing cardiac catheterization. In study 2, 2D-echocardiography and radial dP/dt max were recorded in 54 patients (separate to study 1; 39 men; aged 64 +/- 10 years) at baseline and peak dobutamine-induced stress. Three basal septum measures were taken as being analogous to LV dP/dt max: 1. Peak systolic strain rate; 2. Strain rate (SR-dP/dt max) during isovolumic contraction (IVCT) and; 3. Tissue velocity during IVCT.', 'In study 1 there was a significant difference between resting LV dP/dt max (1461 +/- 383 mmHg s(-1)) and radial dP/dt max (1182 +/- 319 mmHg s(-1); P < 0.001), and a poor, but statistically significant, correlation between the variables (R(2) = 0.006; P < 0.05). Similar results were observed during exercise. In study 2 there were weak (R(2) = -0.12; P = 0.01) to non-significant associations between radial dP/dt max and all echocardiographic measures analogous to LV dP/dt max at rest or peak stress.']
['The predictive role of hemoglobin A1c (HbA1c) on long-term outcomes after coronary artery bypass surgery has not been evaluated.', 'Preoperative HbA1c levels were obtained in 3,201 patients undergoing primary, elective coronary artery bypass surgery at Emory Healthcare Hospitals from January 2002 to December 2006 and entered prospectively into a computerized database. Long-term survival status was determined by cross-referencing patient records with the Social Security Death Index. Log-rank (unadjusted) and Cox proportional hazards regression models (adjusted) were employed to determine whether HbA1c and diabetes mellitus were independent risk factors for reduced long-term survival, adjusted for 29 covariates. Hazard ratios for each unit increase in continuous HbA1c were calculated.', 'Patients with HbA1c of 7% or greater had lower unadjusted 5-year survival compared with patients with HbA1c less than 7% (p = 0.001). Similarly, patients with diabetes mellitus had lower unadjusted 5-year survival compared with patients without diabetes (p < 0.001). After multivariable adjustment, higher HbA1c (measured as a continuous variable) was associated with reduced long-term survival for each unit increase in HbA1c (hazard ratio 1.15, p < 0.001), but preoperative diagnosis of diabetes was not associated with reduced long-term survival after coronary artery bypass surgery (p = 0.41). Other multivariable predictors of reduced long-term survival included age, cerebrovascular disease, elevated serum creatinine, renal insufficiency, congestive heart failure, previous myocardial infarction, chronic lung disease, and peripheral vascular disease.']
['Highlighted text in the Internet (i.e., hypertext) is predominantly blue and underlined. The perceptibility of these hypertext characteristics was heavily questioned by applied research and empirical tests resulted in inconclusive results. The ability to recognize blue text in foveal and parafoveal vision was identified as potentially constrained by the low number of foveally centered blue light sensitive retinal cells. The present study investigates if foveal and parafoveal perceptibility of blue hypertext is reduced in comparison to normal black text during reading.', 'A silent-sentence reading study with simultaneous eye movement recordings and the invisible boundary paradigm, which allows the investigation of foveal and parafoveal perceptibility, separately, was realized (comparing fixation times after degraded vs. un-degraded parafoveal previews). Target words in sentences were presented in either black or blue and either underlined or normal.', 'No effect of color and underlining, but a preview benefit could be detected for first pass reading measures. Fixation time measures that included re-reading, e.g., total viewing times, showed, in addition to a preview effect, a reduced fixation time for not highlighted (black not underlined) in contrast to highlighted target words (either blue or underlined or both).']
['To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients.', 'A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined.', 'We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T.']
['Ghrelin is a hormone that protects against hypoxic injury of cardiac cells by inducing autophagy, but the role of autophagy in sepsis remains unclear. This study aimed to evaluate whether ghrelin could enhance autophagy in rats with intestinal sepsis.', 'The cecal ligation and perforation (CLP) method was used to induce sepsis in Sprague-Dawley rats. The rats were assigned to four groups: normal group, sham-operated group, sepsis group, and Ghrelin-treated group. Sera and small intestinal tissues were collected from all groups. The sepsis was evaluated by histological analysis, and autophagy of small intestinal epithelial cells was assessed by electron microscopy, immunofluorescence, and biochemical methods.', 'The expression of autophagy-associated proteins such as LC3, Atg 7 and Beclin 1 increased by 8h post-CLP and declined to basal levels by 12h post-CLP. The expression of LC3, Atg 7 and Beclin 1 in Ghrelin-treated rats was higher than that in rats with sepsis. Furthermore, compared to rats with sepsis, Ghrelin-treated rats showed significantly reduced intestinal mucosa injury at 20h post-CLP.']
['A randomized trial was conducted to evaluate the impact of a telephone counseling intervention to improve patient adherence to colposcopic examination for suspected cervical intraepithelial neoplasia (CIN).', 'Subjects were lower-income, minority women who missed a scheduled initial appointment for colposcopy at an urban medical clinic. Patients were randomly assigned to either a control condition (n = 42) or a telephone counseling condition (n = 48). The 15-minute, structured telephone counseling intervention protocol addressed educational, psychosocial, and practical barriers to colposcopy adherence.', 'The most common patient-reported barriers to colposcopy adherence included a lack of understanding of the purpose of colposcopy (50%), worry about or fear of cancer (25%), and forgetting (23%). Telephone counseling was found to be highly effective in addressing these barriers and improving adherence to diagnostic follow-up and treatment. Of patients in the control condition, 43% complied with a rescheduled colposcopy appointment, compared with 67% in the telephone counseling condition. Logistic regression analysis indicated that the effect of telephone counseling was independent of sociodemographic confounder variables (odds ratio = 2.6; P less than .003). Additionally, 74% of patients who received the initial telephone counseling adhered to recommended treatment, compared with 53% of patients in the control condition.']
['Early detection and treatment of amblyogenic conditions such as high refractive errors and anisometropia can help prevent the development of amblyopia. The traditional gold standard for the determination of refractive error in pre-school children is retinoscopy. Difficulties with retinoscopy in pre-school children have led to the development of autorefractors that can be free of operator bias and can be used by lay individuals. The Nikon Retinomax Plus handheld autorefractor has proven to be reliable for quick and accurate assessments of refractive errors in children. The Welch Allyn SureSight Vision Screener is a relatively new handheld autorefractor. The present study compares the results of measurements with the Retinomax Plus and the SureSight to the results of cycloplegic retinoscopy in pre-school children.', 'Thirty-five children ranging in age from 3 to 5 years old were subjects. Any subjects with strabismus, amblyopia, nystagmus, or ocular disease were excluded. Refractive error was assessed 30 min after the application of a cycloplegic spray.', 'Both autorefractors showed moderate agreement with cycloplegic retinoscopy results for measurement of spherical equivalent and cylinder power. In addition, the SureSight and the Retinomax Plus sphere and cylinder results showed moderate agreement with each other. Although the mean differences of the spherical equivalents determined were minimal, the 95% confidence intervals were large, which limits the value of the data obtained from each instrument.']
['Silent myocardial ischemia is common in asymptomatic subjects without a prior history of coronary artery disease (CAD) and is associated with increased morbidity and mortality. Our objective was to determine whether endothelial dysfunction is associated with silent myocardial ischemia and whether the association is independent of genetic and familial factors.', 'We examined 416 male monozygotic and dizygotic twins aged 47 to 63 years, free of symptomatic CAD. Subclinical ischemia was diagnosed by [13N] ammonia positron emission tomography at rest and after adenosine stress. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. Generalized estimating equations were used for analysis.', 'Fixed perfusion defects were found in 24 (6%) twins and reversible perfusion defects in 90 (22%) twins, indicating subclinical ischemia. There was an inverse correlation between FMD and the reversible perfusion defect score (r = - 0.14, p=0.01) but not the fixed defect score (r= -0.017, p=0.73). From the lowest to the highest quartile of FMD, the prevalence of reversible defects decreased 28% to 14%, p=0.008. In multivariable analysis, reversible defects were significantly associated with each quartile of decreasing FMD (OR =1.3; 95% 1.1, 2.5). In 54 twin pairs discordant for endothelial dysfunction (FMD ≤ 7% dilation from baseline), twins with endothelial dysfunction had 9% higher likelihood of having perfusion defects than their co-twins without endothelial dysfunction (p=0.041).']
['Hepatitis E virus (HEV) infection is a significant public health concern and has been identified as a zoonotic infection.', 'Since no reports have characterized the epidemiological and genotypic features of HEV infections in Macaca mulatta (rhesus macaques) from Yunnan, China, where swine HEV infections are endemic, we aimed to investigate these characteristics.', 'Seroepidemiological and molecular characterization of HEV in both Macaca mulatta and pigs from the Yunnan province of China were conducted using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-nested PCR (RT-nPCR). Four hundred and eighty-two stool samples (320 from Macaca mulatta and 162 from pigs) and 92 serum samples (all from Macaca mulatta) were collected for the detection of HEV RNA and anti-HEV antibodies (IgG/IgM).', 'Thirty-three rhesus macaques (35.87%) were positive for HEV IgG. Of these, 3 were also positive for HEV IgM. Four different strains of swine HEV RNA were detected in pigs; however, we failed to detect any in Macaca mulatta.']
["Environmental enrichment (EE) in laboratory animals improves neurological function and motor/cognitive performance, and is proposed as a strategy for treating neurodegenerative diseases. EE has been investigated in the R6/2 mouse model of Huntington's disease (HD), where increased social interaction, sensory stimulation, exploration, and physical activity improved survival. We have also shown previously that HD patients and R6/2 mice have disrupted circadian rhythms, treatment of which may improve cognition, general health, and survival.", 'We examined the effects of EE on the behavioral phenotype and circadian activity of R6/2 mice. Our mice are typically housed in an "enriched" environment, so the EE that the mice received was in addition to these enhanced housing conditions. Mice were either kept in their home cages or exposed daily to the EE (a large playground box containing running wheels and other toys). The "home cage" and "playground" groups were subdivided into "handling" (stimulated throughout the experimental period) and "no-handling" groups. All mice were assessed for survival, body weight, and cognitive performance in the Morris water maze (MWM). Mice in the playground groups were more active throughout the enrichment period than home cage mice. Furthermore, R6/2 mice in the EE/no-handling groups had better survival than those in the home cage/no-handling groups. Sex differences were seen in response to EE. Handling was detrimental to R6/2 female mice, but EE increased the body weight of male R6/2 and WT mice in the handling group. EE combined with handling significantly improved MWM performance in female, but not male, R6/2 mice.']
['U.S. Navy policy requires Chlamydia trachomatis screening of all women upon entry to recruit training in conjunction with an educational session, and yearly screening thereafter until age 25. Army policy directs only annual screening of asymptomatic women aged <25. Hence, screening of Army recruits may not occur for up to 12 months following accession. Using routinely collected surveillance data, the rates of outpatient pelvic inflammatory disease (PID) following accession into the Army or Navy were compared to assess the potential implications of these policies.', 'The population at risk comprised active-component women aged <25 who accessioned to either the U.S. Army or Navy between January 1, 2001, and December 31, 2005. Subjects were followed up to 60 months from accession, either until a first outpatient PID diagnosis occurred or they departed from military service. Data were collected from 2001 to 2006 and analyzed in 2007. Multiple Poisson regression was used to assess the effects of potentially important covariates. Time-to-event analysis was employed to characterize risk over time.', 'There were 1276 and 546 incident outpatient diagnoses of PID among 58,088 Army and 33,046 Navy accessions during 93,918 and 65,863 person-years of follow-up, respectively. The crude incident rate was 64% higher in the Army (13.6/1000 person-years) than the Navy (8.3/1000 person-years). Risk for the Army increased soon after accession, followed by a decline, while risk for the Navy remained comparatively uniform.']
['Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS.', 'To determine if certain polymorphisms in the tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) cytokines are overrepresented in a cohort of patients with MDSs.', 'DNA was isolated from the peripheral blood or bone marrow aspirate of 21 patients with MDS. The genotypes for 4 different polymorphisms, 2 in TNFalpha and 2 in TGFbeta1, were determined using single-specific-primer polymerase chain reaction. The allele and genotype frequencies were compared with similar populations in the National Cancer Institute SNP500 database.', 'In our MDS population, the -308A/A genotype of the TNFalpha gene and the TGFbeta1 allele +29T and genotype +29T/T, each associated with higher levels of expression, were overrepresented in our MDS population.']
['Aberrant signalling along the p21ras/MAP kinase pathway has been demonstrated in systemic lupus erythematosus (SLE).', 'To determine whether expression and activity of the MAP kinases ERK and JNK reflect disease activity in patients with SLE.', 'Blood samples of 42 outpatients with SLE were prospectively collected during four consecutive visits. The control group included 20 healthy subjects. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Expression of total ERK and JNK kinases and their active forms (pERK and pJNK) was determined in whole protein lysates of peripheral blood mononuclear cells.', 'The mean levels of the active kinases pERK and pJNK were significantly increased in patients with active disease (SLEDAI 4-20) as compared with patients with inactive disease (SLEDAI 0-3), p = 0.04, as well as with healthy controls, p = 0.03 and p = 0.003 for pERK and pJNK, respectively. The percentage of activated forms of ERK and JNK of the total expression of these MAP kinases was also gradually increased, reaching 50% for pERK and >40% for pJNK in patients with SLE with moderate-to-severe disease (SLEDAI 7-20), p = 0.005, p = 0.005 and p = 0.02, p = 0.05 as compared with controls and inactive patients, respectively. A decrease of more than three SLEDAI points was associated with a significant reduction in the expression of both total and activated forms of ERK and JNK, p = 0.03, p = 0.01, respectively.']
['High levels of cardiopulmonary fitness (VO2max) are associated with reduced risk of cardiovascular morbidity and mortality, but little is known to what extent this is related to the effects of cardiopulmonary fitness on atherosclerosis and arterial stiffness. Moreover, the time course of these relationships needs to be elucidated. We sought to investigate (i) the cross-sectional relationship between VO2max and carotid atherosclerosis and carotid and femoral arterial stiffness at age 36, as well as (ii) the relationship between VO2max during adolescence (13-16 years) and the same arterial properties at age 36 (prospective analyses).', 'Cross-sectional analyses consisted of 351 subjects (183 women) and the prospective analyses of a subpopulation of 154 subjects (79 girls). Arterial properties were assessed noninvasively by ultrasound imaging; VO2max was measured with a maximal running text on a treadmill with direct measurements of oxygen uptake.', 'After adjustment for confounding by other known risk factors, current and adolescent levels of VO2max were independently associated with carotid intima-media thickness (beta = -0.288, P = 0.004 and beta = -0.381, P = 0.012) in men, and with the diameter of the femoral artery (beta = 0.375, P < 0.001 and beta = 0.252, P = 0.026, respectively) in both sexes. Current levels of VO2max were positively associated with the compliance of the carotid and the femoral arteries (beta = 0.186, P = 0.023 and beta = 0.183, P = 0.033, respectively), and with the distensibility of the carotid (beta = 0.162, P = 0.047) but not the femoral artery.']
['To investigate whether coffee consumption is associated with 10-year cognitive decline in elderly men, as results of previous studies obtained hitherto have been controversial and prospective information on this association has been lacking.', 'Six hundred and seventy six healthy men born between 1900 and 1920 from Finland, Italy and the Netherlands participated in a 10-year prospective cohort study. Cognitive functioning was assessed using the Mini-Mental State Examination (0-30 points, with a higher score indicating better cognitive performance). Coffee consumption was estimated in cups per day. A mixed longitudinal model was used to investigate the association between baseline coffee consumption and 10-year cognitive decline. Multiple adjustments were made.', 'Men who consumed coffee had a 10-year cognitive decline of 1.2 points (4%). Non-consumers had an additional decline of 1.4 points (P<0.001). An inverse and J-shaped association was observed between the number of cups of coffee consumed and cognitive decline, with the least cognitive decline for three cups of coffee per day (0.6 points). This decline was 4.3 times smaller than the decline of non-consumers (P<0.001).']
['Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported.', 'Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting.', 'EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise.']
["To evaluate the effect of early 'aggressive' drug treatment on radiographic progression in patients with recent-onset rheumatoid arthritis (RA), compared to conventional stepwise increasing intensity of treatment.", "Prospective follow-up study with an experimental group and a historical control group both divided into a high-risk subgroup and a low-risk subgroup, based on prognostic factors. The effect of the 'aggressive' and the conventional treatment strategy was compared between both high-risk groups; the low-risk groups, both treated according to the conventional treatment strategy, were used to ensure internal consistency between the experimental and the historical groups.", 'A total of 228 consecutive patients with recent-onset RA (complaints < 1 yr at study entry).', "The 'aggressive' drug treatment consisted of institution of relatively fast-acting disease-modifying anti-rheumatic drugs (DMARDs) (sulphasalazine, methotrexate) immediately after diagnosis, and rapid adjustment of dosage and/or drug in the case of insufficient response as measured by a change in C-reactive protein (CRP) level. Radiographic damage was assessed according to a modified version of Sharp's method and cumulative disease activity expressed as CRP-area under the curve (CRP-AUC). The occurrence of side-effects was also evaluated.", "After 2 yr of follow-up, comparison of the two high-risk subgroups showed the radiographic progression in the 'aggressively' treated subgroup to be significantly lower than that in the control group [Sharp score: median (range) 26 (0-100) vs 35 (1-188); P = 0.03]. Cumulative CRP values were also significantly lower than in the control high-risk subgroup [CRP-AUC: median (range) 1963 (212-8515) vs 3025 (46-15 632) mg.week/1; P = 0.002). This was achieved without an increase in the occurrence of side-effects. There was no difference between the two low-risk subgroups with regard to entry characteristics, CRP-AUC values or radiological progression, indicating comparability between the two groups."]
['Down-regulation of E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT). EMT progression in cancer cells is associated with the loss of certain epithelial markers and the acquisition of a mesenchymal phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis in colon cancer. This study investigated the relationship between E-cadherin and COX-2 in colon cancer cells and human colon tumors.', 'Colon cancer cell lines and immunohistochemistry were used.', "E-cadherin expression was inversely related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic expression of COX-2 or Snail reduced E-cadherin and induced a scattered, flattened phenotype with few intercellular contacts in colon cancer cells. Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase expression, and increased the cells' motility. In addition, exposure to prostaglandin E(2) increased Snail expression and cell motility, and decreased E-cadherin expression. Membranous E-cadherin expression was lower in adenomas and cancers than in the adjacent, non-neoplastic epithelium. In contrast, the expressions of Snail and COX-2 were higher in cancers than in normal tissues and adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E-cadherin expression. Moreover, COX-2 expression was related to higher tumor stages and was significantly higher in nodal metastatic lesions than primary cancers."]
['Ghrelin is a potent gastric-derived GH-releasing peptide. How ghrelin interacts with sex steroids, GHRH, and somatostatin (SS) is not known.', "Our objective was to test the hypotheses that ghrelin's interactions with GHRH (synergistic) and SS (disinhibitory) are ghrelin dose-dependent and amplified by estrogen. SUBJECTS, SETTING, AND DESIGN: Healthy postmenopausal women were treated with placebo (n=12) or 17β-estradiol (E2) (n=12) at the Center for Translational Science Activities in a randomized double-blind prospective study.", 'Ghrelin dose-dependence was assessed by nonlinear curve fitting of the relationship between deconvolved GH secretory-burst mass and 5 randomly ordered ghrelin doses (0, 0.03, 0.135, 0.6, and 2.7 μg/kg bolus iv) during saline, GHRH, and SS infusion.', 'Under placebo, neither GHRH nor SS altered the ED50 of ghrelin (range 0.64-0.67 μg/kg). Under E2 (median E2 88 pg/mL), the ED50 of ghrelin declined in the presence of GHRH to 0.52 μg/kg. In contrast, the efficacy of ghrelin rose markedly during GHRH vs saline exposure with and without E2: placebo and saline 52±1.0 vs GHRH 173±3.8 μg/L; and E2 and saline 56±0.90 vs GHRH 174±3.7 μg/L. Sensitivity to ghrelin was similar under all conditions.']
['Recent studies suggest the role of liver enzymes, such as serum gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) as the predictor for future development of metabolic syndrome (MetS), diabetes and cardiovascular disease in epidemiologic studies. We hypothesized that serum concentrations of GGT and ALT are associated with the development of MetS, according to newly recommended criteria from International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition in Koreans.', 'A total of 15,250 males (mean 38 y) and 6280 females (mean 41 y) who visited the Health Promotion Center at Kangbuk Samsung Hospital for medical check-up in 2002, were followed-up after 4 y. We analyzed the development of MetS in their follow-up data in 2006.', 'When the subjects were divided into quartiles by the baseline GGT levels, the odds ratio for the MetS defined by both criteria across the quartile groups increased as the quartile groups increased in both gender groups. This association remained significant even after adjustment for confounding factors, such as, age, alcohol intake, smoking status, physical activity, ALT, fasting insulin and HOMA-IR. Serum ALT concentration also showed significantly positive correlation with development of MetS defined by the two criteria even after adjustment for age and GGT in both gender groups. In addition, risk for the individual MetS components increased as the baseline GGT concentrations increased, except low high-density lipoprotein cholesterol (HDL-C) in female group. In receiver operating characteristic (ROC) curves, the area under the curves (AUC) of GGT and ALT to predict future MetS by both criteria was larger than the AUCs of blood pressure, fasting glucose and HDL-C.']
['Ischemic mitral regurgitation (IMR) limits life expectancy and can lead to postinfarction global left ventricular (LV) dilatation and remodeling, the pathogenesis of which is not completely known. We tested the hypothesis that IMR perturbs adjacent myocardial LV systolic strains.', 'Thirteen sheep had three columns of miniature beads inserted across the lateral LV wall, with additional epicardial markers silhouetting the ventricle. One week later posterolateral infarction was created. Seven weeks thereafter, the animals were divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative histology were used to calculate ventricular volumes, transmural myocardial systolic strains, and systolic fiber shortening.', 'Seven weeks after infarction, end-diastolic (ED) volume increased similarly in both groups, end-systolic (ES) E13 (circumferential-radial) shear increased in both groups, but more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12 (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs -0.01, p < 0.005). There were no significant differences in ED or ES remodeling strains or systolic fiber shortening between IMR(-) and IMR(+).']
['Drug-coated balloons (DCB) are being increasingly used in interventional cardiology. The effect of DCB on acute changes of coronary flow reserve (CFR) has never been reported.', 'Patients with in-stent restenosis or with contraindication for use of clopidogrel were included in this study. The FloWire was used to assess CFR before and immediately after conventional balloon angioplasty and after the use of In.Pact, a paclitaxel-coated balloon. In a sub-selection of patients, CFR was measured immediately and then 2, 5, and 10 min post-DCB.', 'Thirty patients (18 males, 60%) with a total of 32 lesions were studied. Comparison of CFR pre- and post-conventional balloon angioplasty was not statistically significant (P = 0.95). CFR dropped significantly after the use of In.Pact (n = 32, 1.59 ± 0.49 vs. 1.22 ± 0.28, P < 0.0001) and showed a statistically significant improvement over 10 min in a subset of patients (n = 6, P = 0.01). Implantation of a coronary stent after the use of In.Pact rapidly improved CFR (n = 10, P = 0.0004).']
['The brief incubation of opossum kidney (OK) cells with low P(i) results in Na+/P(i) cotransport up-regulation and in substantial, but transient, cytoskeletal reorganization. In this study, we examined signaling events involved in the depolymerization of microfilaments.', "Confocal laser scanning microscopy, immunoblot and immunoprecipitation experiments revealed villin co-localization with mainly actin short filaments and monomers, indicating that under the conditions used, villin acted as an actin-severing protein. Further analysis revealed that low concentrations of extracellular phosphate resulted in phospholipase Cgammal (PLC-gammal) translocation to the actin cytoskeleton, without increases in its tyrosine phosphorylation. Additionally, tyrosine phosphorylation of a portion of insoluble villin was increased; whereas, only tyrosine phosphorylated villin associated with PLC-gammal. Although, tyrosine phosphorylation of PLC-gammal was not observed during Na+/P(i) cotransport up-regulation, genistein treatment abolished the enzyme's translocation to the actin cytoskeleton, as well as its association with villin. In addition, villin was found to associate with the 85-KDa subunit (p85) of phosphatidylinositol (PI)-3 kinase, concomitant with PLC-gammal, in the cytoskeletal fraction of Na+/P(i) cotransport up-regulated cells."]
['The aim of this study was to investigate the role of\xa0matrix metalloproteinase-9 (MMP-9) C-1562T and 279R/Q (836G>A) polymorphisms in the development of chronic obstructive pulmonary disease (COPD) in Tunisians and to determine their impact on disease progression and airflow obstruction.', 'Pulmonary functional tests were evaluated by body plethysmography. MMP-9 genotypes were determined in patients with\xa0COPD\xa0(n\xa0=\xa0138) and healthy controls (n\xa0=\xa0216) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum MMP-9 and interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assays (ELISA) and activity of MMP-9 was evaluated by gelatin zymography.', 'No significant association was found between genetic variations in MMP-9 C-1562T and 279R/Q polymorphisms and the risk of development of COPD. However, a significant correlation was retrieved between the 279\xa0R/Q polymorphism and disease severity (P\xa0=\xa00.02). In addition, homozygous Q (A) genotype was associated with a poorer lung function with a fall in forced expiratory volume in 1\xa0s (FEV1) (%) and forced vital capacity (FVC%) among COPD patients compared with both AG and GG individuals (52.06\xa0±\xa019.6 vs. 59.08\xa0±\xa017.19, P\xa0=\xa00.03 and 72.41\xa0±\xa021.42 vs. 82.98\xa0±\xa016.48, P\xa0=\xa00.002, respectively). Using ELISA, a higher level of MMP-9 was found in patients with the CT genotype (P\xa0=\xa00.03), while no significant impact of the 279R/Q polymorphism was observed (P\xa0=\xa00.48). In contrast, by using zymography gel analysis, MMP-9 activity was enhanced in individuals carrying the R(G) allele in comparison with those homozygous for the Q(A) variant (P\xa0=\xa00.02).']
["Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify 'druggable' pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus.", "We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in 'hot spot' regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA).", 'Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice.']
['The aim of this study was to investigate the relationship between dietary insulin load (DIL) and insulin index (DII) and the risk of insulin resistance in Tehranian adults.', 'In this study, 927 men and women, aged 22-80 years, participated in Tehran Lipid and Glucose Study were included. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up. Usual dietary intakes were measured using a validated 168 item semi-quantitative food frequency questionnaire and DIL and DII were calculated. Logistic regression models were used to estimate the occurrence of the IR across tertile categories of DIL and DII with adjustment for potential confounding variables.', 'Mean age of participants was 40.71\u2009±\u200912.14 y, and mean body mass index (BMI) was 27.23\u2009±\u20094.9\xa0kg/m(2), at baseline. Mean of DIL and DII was 937\u2009±\u2009254 and 84.0\u2009±\u20096.3. Participants with higher DIL had higher weight and waist circumference at baseline (P\u2009<\u20090.05). A borderline positive association was observed between DII and the risk of insulin resistance in fully adjusted model (odds ratio\u2009=\u20091.66, 95\xa0% confidence interval\u2009=\u20090.96-2.86, P for trend\u2009=\u20090.06). After adjustment of potential confounders, highest compared to the lowest tertile of DIL was also significantly associated with increased risk of insulin resistance (odds ratio\u2009=\u20091.69, 95\xa0% confidence interval\u2009=\u20091.01-2.89, P for trend\u2009=\u20090.06).']
["The authors' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder (PTSD) and substance abuse (seeking safety) with a manualized cognitive behavior therapy that addresses only substance abuse (relapse prevention) and with standard community care for the treatment of comorbid posttraumatic stress disorder (PTSD) and substance use disorder.", 'One hundred seven women from an urban, low-income population who had comorbid PTSD and substance use disorder were randomly assigned to receive the two kinds of cognitive behavior therapy or received standard community treatment. Participants were recruited from both community and clinical populations and evaluated with structured clinical instruments. Forty-one women received seeking safety therapy, 34 received relapse prevention therapy, and 32 received standard community care.', 'At the end of 3 months of treatment, participants in both cognitive behavior therapy conditions had significant reductions in substance use, PTSD, and psychiatric symptoms, but community care participants worsened over time. Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group.']
['the transurethral resection of prostate TURP is the elective treatment for the small and medium adenomas. In this study they analyse the effectiveness, the results and the postoperative morbidity in the resection of the great adenomas.', 'We study 340 patients with great adenomas and symptomatic infravesical obstruction that were operated with the low hydraulic pressure RTUP between August of 1999 and June of 2006.', 'Average Age of the patients 69 years (range 51-89). Prostate volume by TRUS, 107 ml (70-204). PSA 7,94 ng/ml (0,71-26,4). Weight of the resected fragments: 74,5gr. (50-160), time of the intervention 65 min. (35-155), postoperative urethral catheterisation 1.7 days (1-8), suprapubic derivation 6.5 days (5-15), the duration of hospital stay after surgery were 8 days (7-16), peak flow pre-op. 11.2 ml/sec. (5-15,7), post-operative 19.7 ml/sec. (7-41,3). There were no cases of TURP syndrome in this group. Operative complications: Urinary infection without fever (bacteria >100.000) 95 patients (27.9%), bladder derivation by preoperative urinary retention 53 patients (15,6%). 18 patients (5,3%) with postoperative urinary retention. 11 patients (3,2%), with infection and fever >38 degrees C. 7 patients (2%) with postoperative bladder bleeding, 2 patients (0,6%) with urethral lesion. 1 patient (0.3%), with massive scrotal hematoma (after vasectomy). Control of the pre and post operative hemoglobin: Hemoglobin pre-op 15 g/dl (12-19,3), hemoglobin post-op 11,5 g/dl (7,6-16,4), difference of (- 3,5g/dl) 23,3%. In only 29 patients (8.5%) it was necessary to carry out a sanguineous transfusions (heterolog) of 2 to 4 EC (500 ml), the TRUS was 125 ml, weight of the fragments 90 gr. (52-140), the hemoglobin pre-op was 14,72g/dl and post-op of 8,8g/dl with a difference of (- 5,92g/dl) 40.2%.']
['Diabetic patients also show hypercoagulability and platelet hyperaggregability, with increased levels of platelet activation-markers such as P-selectin (CD62P) and platelet-derived microparticles. We investigated the effects of losartan and simvastatin on circulating levels of platelet activation markers, microparticles, soluble selectins, and soluble cell adhesion molecules in hypertensive and hyperlipidemic patients with or without Type 2 diabetes.', 'The subjects included 25 normotensive healthy controls and 41 hypertensive patients. The 41 hypertensive patients were divided into three groups: group A had hypertension and hyperlipidemia (n = 11), group B had hypertension and Type 2 diabetes (n = 14), and group C had hypertension, hyperlipidemia, and diabetes (n = 16). Losartan was administered to all of the patients at a dose of 50 mg/day for 24 weeks. In addition, simvastatin was administered to the hyperlipidemic patients at a dose of 10 mg/day for 24 weeks.', 'There were significant differences in the levels of CD62P, CD63, PAC-1, platelet microparticles, endothelial microparticles, sE-selectin, and sVCAM-1 between the hypertensive patients and healthy controls. These markers were all significantly increased in hypertensive and hyperlipidemic patients with Type 2 diabetes. In hypertensive patients with diabetes, CD62P, CD63, PAC-1, platelet and endothelial microparticles, and soluble adhesion markers were all decreased by losartan monotherapy. The decrease of each marker in hypertensive and hyperlipidemic patients given combined therapy with losartan plus simvastatin was greater among those with than without Type 2 diabetes. Low-density lipoprotein was decreased significantly by simvastatin and was correlated with CD62P or platelet microparticles in all of the patients.']
['The Lewis rat among highly inbred strains exhibits significant airway hyperresponsiveness (AHR) following intravenous administration of Sephadex G-200 (Sephadex). The aim of this study was to investigate the association of Sephadex-induced AHR with changes in airway inflammation in Lewis rats.', 'A suspension (0.5 mg/ml/rat) of Sephadex was intravenously administered to male Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin, bronchoalveolar lavage (BAL) and histological study were performed on day 2-11.', 'Significant AHR induced by Sephadex was recognized on day2 (p < 0.05), and AHR reached a maximum on day 7 (p < 0.001). In the BAL study, eosinophils increased on day2 (p < 0.01) with a peak on day 5 (p < 0.05). In the histological study, we found Sephadex beads trapped in small arteries of the lung and granulomatous arteritis on day 2 or later. Pulmonary granulomas, horseshoe-shaped multinuclear giant cells, eosinophils and goblet cell hyperplasia were observed on day 2, and the degree became intense on day 5-7. GCC-AP0341 (10 mg/kg, i.p. x 3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but it did not inhibit AHR. The compound also inhibited pulmonary granulomas and goblet cell hyperplasia.']
['The prognostic impact of reduced glomerular filtration rate (GFR) in chronic heart failure (CHF) is increasingly recognised, but little is known about tubular damage in these patients.', 'To investigate the prevalence of tubular damage, and its association with GFR, and prognosis in patients with CHF.', 'In 90 patients with CHF, GFR and effective renal plasma flow (ERPF) were measured ([(125)I]iothalamate and [(131)I]hippuran clearances). The tubular markers neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as well as urinary albumin excretion were determined in 24 h urine collections. Mean GFR was 78+/-26 ml/min/1.73 m(2). Urinary NGAL (175 (70-346) microg/g creatinine (gCr)), NAG (12 (6-17) U/gCr) and KIM-1 (277 (188-537) ng/gCr) levels were increased compared with 20 healthy controls (all p<0.001). Urinary NAG, but not NGAL or KIM-1 correlated with GFR (r=-0.34, p=0.001) and ERPF (r=-0.29, p=0.006). Both NAG (r=0.21, p=0.048) and KIM-1 (r=0.23, p=0.033) correlated with plasma N-terminal pro-brain natriuretic peptide levels. Both urinary KIM-1 (HR=1.15 (95% CI 1.02 to 1.30) per 100 ng/gCr increase, p=0.025) and NAG (HR=1.42 (95% CI 1.02 to 1.94) per 5 U/gCr increase, p=0.039), were associated with an increased risk of death or heart failure hospitalisations, independent of GFR.']
['Painless myocardial ischemia (PMI) is associated with poor outcomes in the general population. We hypothesized that the presence of PMI is inversely related to the level of kidney function and is associated with impaired survival in chronic kidney disease (CKD).', 'A total of 356 patients who underwent percutaneous coronary intervention were assessed for PMI, which was defined as the absence of chest pain in response to balloon dilation of the affected vessel. Cox proportional hazards analysis was used to calculate 10-year all-cause mortality.', 'There was an increase in PMI occurrence by strata of estimated glomerular filtration rate (eGFR), whereby PMI was present in only 20.6% of individuals with eGFR ≥ 90 ml/min/1.73 m(2), but was found in 50.0% of individuals with eGFR <30 ml/min/1.73 m(2) (p = 0.004 for trend). Classification of individuals as having either CKD or PMI showed significant differences in adjusted mortality between groups (p < 0.001 for trend), with individuals having both CKD and PMI demonstrating the highest 10-year mortality. Compared to individuals with neither CKD nor PMI, individuals with CKD and no PMI had a hazard ratio (HR) for mortality of 1.64 (95% CI: 1.03-2.63, p = 0.038), while individuals with both PMI and CKD had an HR of 2.08 (1.30-3.33, p = 0.002).']
['Different factors such as impression techniques and materials can affect the passive fit between the superstructure and implant. The aim of this study was to determine the effect of different impression materials and techniques on the dimensional accuracy of implant definitive casts.', 'Four internal hex implants (Biohorizons Ø4 mm) were placed on a metal maxillary model perpendicular to the horizontal plane in maxillary lateral incisors, right canine and left first premolar areas. Three impression techniques including open tray, closed tray using ball top screw abutments and closed tray using short impression copings and two impression materials (polyether and polyvinyl siloxane) were evaluated (n = 60). The changes in distances between implant analogues in mediolateral (x) and anteroposterior (y) directions and analogue angles in x/z and y/z directions in the horizontal plane on the definitive casts were measured by coordinate measuring machine. The data were analyzed by multivariate two-way analysis of variance and one sample t-test (α = 0.05).', 'No statistical significant differences were observed between different impression techniques and materials. However, deviation and distortion of definitive casts had a significant difference with the master model when short impression copings and polyvinyl siloxane impression material were used (P < 0.05). In open tray technique, there was a significant difference in the rotation of analogs compared with the master model with both impression materials (P < 0.05).']
['The GlideScope videolaryngoscope allows equal or superior glottic visualization compared with direct laryngoscopy, but predictive features for difficult GlideScope intubation have not been identified. We undertook this prospective study to identify patient characteristics associated with difficult GlideScope intubation.', 'Demographic and morphometric factors were recorded preoperatively for 400 patients undergoing anesthesia with endotracheal intubation. After induction, direct laryngoscopy was performed in all patients to assess the Cormack and Lehane grade of glottic visualization followed by GlideScope intubation. The number of attempts and time needed for intubation were recorded. Univariate and multivariate analyses were performed to identify the characteristics associated with difficult GlideScope intubation.', 'Intubation required 1, 2, and 3 attempts in 342, 48, and 9 participants, respectively, with one failure. Mean time for intubation was 21 +/- 14 s. After univariate analysis, the following characteristics were significantly correlated (P < 0.05) with longer time to intubate and/or multiple attempts: older age, male sex, history of snoring, high Mallampati class, small mouth opening, short sternothyroid and manubriomental distances, large neck circumference, high upper lip bite test score, and high Cormack and Lehane grade during direct laryngoscopy. However, after introducing these variables in nominal logistic and proportional hazard multiple regression models, only high Cormack and Lehane grade during direct laryngoscopy, high upper lip bite test score, and short sternothyroid distance were significantly associated with multiple attempts or lengthier intubations.']
['Stem cell factor (SCF) has already been shown to participate in the regulation of erythro- and granulopoiesis. The aim of this study was to define the possible role of SCF in the regulation of megakaryocytopoiesis.', 'Stem cell factor activity has been assessed in an in vivo murine model, in which different doses of the factor were either given alone or in association with recombinant human erythropoietin (rhEpo). Mice were sacrificed after a six-day treatment to evaluate the effect of SCF on the number of bone marrow and spleen colony-forming units-megakaryocyte (CFU-Mk), and after a two-day treatment for evaluation of thrombopoietin-like activity.', 'We found that SCF induces a dose-related increase in the number of CFU-Mk in both the bone marrow and spleen of the treated mice, and that in the range of the doses used (from 25 to 200 mg/kg/day) the greatest activity was observed when a dose of 200 mg/kg/day was injected. The effect was enhanced by adding rhEpo to optimal SCF concentrations. SCF also stimulated megakaryocyte maturation as assessed by the megakaryocyte number, the size of acetylcholinesterase-positive cells, 35Sulphur (35S) incorporation into the newly formed platelets. All these parameters were only minimally affected by the addition of rhEpo.']
['We set out to define the characteristics of humoral autoimmunity against ZnT8 in children and adolescents with newly diagnosed T1D in relation to age and metabolic status at diagnosis, human leucocyte antigen (HLA) genotype and family history of T1D.', 'A total of 2115 subjects <15\u2009years of age were analysed for antibodies against zinc transporter 8, ICA, GADA, IAA, IA-2A, HLA DR-DQ genotype, blood pH, plasma glucose and β-hydroxybutyrate concentrations. Their family history of T1D was also recorded.', 'Zinc transporter 8 antibodies (ZnT8A) were detected in 63% of the cases. ZnT8A positivity was associated with older age at diagnosis (mean 8.2\u2009years versus 7.5\u2009years, p\u2009<\u20090.001). Seven subjects (0.3%) had ZnT8A as their single autoantibody. Diabetic ketoacidosis at diagnosis was less common among subjects with ZnT8A than among those without (16% versus 20%, p\u2009=\u20090.012). The prevalence of ZnT8A was decreased in DR3/DR4 heterozygotes when compared with those with other DR combinations (p\u2009<\u20090.001). Subjects with the neutral DR13-DQB1*0604 haplotype tested more frequently positive for ZnT8A than the rest of the population (p\u2009<\u20090.001). A positive family history of T1D showed no association with ZnT8A prevalence or levels.']
['To assess the risk for type 2 diabetes (T2D) and cardiovascular disease (CVD) among employees of a Finnish airline; to study the association of shift work with T2D and CVD risk; and to test the feasibility of risk screening in occupational health care setting.', 'Altogether 4169 employees were invited for a health check-up and 2312 participated in this study. The check-up included physical examinations, questionnaires on working hours, sleep, and lifestyle, diabetes risk score FINDRISC, and blood tests. Lifestyle counselling was offered for those with increased T2D risk.', 'Altogether 15% of participants had a high T2D risk (FINDRISC≥15 and/or elevated, but non-diabetic blood glucose), and a further 15% had a moderate T2D risk (FINDRISC 10-14 and normal blood glucose). Of those 60% agreed to attend lifestyle counselling. Metabolic syndrome was more common, lipid profile more unfavorable and hsCRP higher by increasing FINDRISC score category. Risk factor profiles linked to shift work status were not self-evident.']
['There is evidence that acutely elevated blood pressure (BP) after stroke is associated with increased cerebral hemorrhage and edema. Previous experiments in our laboratory have shown that candesartan 1 mg/kg administered after reperfusion in a model of hypertension after experimental ischemic stroke reduces neurovascular damage and improves outcome. These results could be either mediated by BP lowering or a BP-independent cerebrovascular protective effect.', 'To determine the contribution of BP lowering to the neurovascular protection previously reported with candesartan after stroke.', 'Male Wistar rats (280-305 g) underwent 3 h of middle cerebral artery occlusion (MCAO). At reperfusion, either hydralazine 1 mg/kg (n = 8), enalapril 5 mg/kg (n = 7) or enalapril 10 mg/kg (n = 8) were administered intravenously. BP was measured by telemetry for 2 days before and 24 h after MCAO. After neurological function was assessed, brain tissue was processed for infarct size and hemoglobin content analyses.', 'Mean arterial pressure (MAP) increased from 92 to 124 mmHg immediately upon MCAO and decreased to 112 mmHg after reperfusion, remaining elevated for 24 h (P < 0.0001) in the saline group. Hydralazine reduced MAP (P = 0.048) and infarct size (53 versus 30%, P = 0.0083), and there was a trend towards decreased hemoglobin content. Enalapril 5 mg/kg did not significantly change MAP or other outcomes. Enalapril 10 mg/kg reduced MAP (P < 0.0001) and infarct size (53 versus 29%, P = 0.003). There was an intermediate effect on both hemoglobin content and neurological function, neither one was significant. The time course of BP lowering varied with each treatment.']
['The human pathogen Mycobacterium tuberculosis (Mtb) has the originality of possessing a multifunctional mega-enzyme FAS-I (Fatty Acid Synthase-I), together with a multi-protein FAS-II system, to carry out the biosynthesis of common and of specific long chain fatty acids: the mycolic acids (MA). MA are the main constituents of the external mycomembrane that represents a tight permeability barrier involved in the pathogenicity of Mtb. The MA biosynthesis pathway is essential and contains targets for efficient antibiotics. We have demonstrated previously that proteins of FAS-II interact specifically to form specialized and interconnected complexes. This finding suggested that the organization of FAS-II resemble to the architecture of multifunctional mega-enzyme like the mammalian mFAS-I, which is devoted to the fatty acid biosynthesis.', 'Based on conventional and reliable studies using yeast-two hybrid, yeast-three-hybrid and in vitro Co-immunoprecipitation, we completed here the analysis of the composition and architecture of the interactome between the known components of the Mtb FAS-II complexes. We showed that the recently identified dehydratases HadAB and HadBC are part of the FAS-II elongation complexes and may represent a specific link between the core of FAS-II and the condensing enzymes of the system. By testing four additional methyltransferases involved in the biosynthesis of mycolic acids, we demonstrated that they display specific interactions with each type of complexes suggesting their coordinated action during MA elongation.']
['ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV(1)) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33.', 'To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene-environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort.', 'Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV(1) and BHR at age 8 years; asthma was based on questionnaire data at age 8.', 'In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV(1)% predicted.']
['Maspin is a 42 kDa protein known to act as a tumor suppressor. Although its function has not been fully elucidated, numerous reports have investigated the prognostic impact of maspin in patients with several types of cancer. However, there have been no reports on the association between maspin expression and the prognosis of patients with soft tissue sarcomas (STS). The aim of this study was thus to explore the association of maspin expression with the prognosis of patients with STS.', "One-hundred and eight paraffin-embedded STS tissue samples were immunohistochemically analyzed using antibodies for maspin and Ki-67 antigen. The patients were followed up for 1 to 300 months (median: 33 months) and the prognostic value was evaluated by log-rank test and Cox's regression hazard model.", "Cytoplasmic maspin expression was observed in 48.1% of specimens, and was significantly correlated with a higher FNCLCC grade (P = 0.002) and the presence of distant metastases (P = 0.001), and those with cytoplasmic maspin expression had both shorter disease-free survival (DFS) and overall survival (OS) by log-rank test (P <0.001, P = 0.001, respectively). By Cox's multivariate analysis, the presence of distant metastases was the only prognostic factor for DFS and OS."]
['Uninsured and underinsured patients are reported to be at an increased risk for impaired access to healthcare, delayed medical treatment, and the receipt of substandard care. These differences in care may result in disparities in surgical outcomes among patients with different types of insurance. In the current study, the authors examined associations between the insurance provider and short-term surgical outcomes after surgery for colorectal carcinoma and evaluated the extent to which two risk factors (comorbid disease and admission type) might explain any observed association.', 'The authors conducted a nationally representative retrospective cohort study of 13,415 adults ages 40-64 years who were admitted for surgery for colorectal carcinoma to hospitals that participated in the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project National Inpatient Sample, releases 6 and 7, in 1997 and 1998. Multivariate logistic regression models were developed to describe the correlations between insurance status and the risks of a postoperative complication or postoperative death after adjustment for socioeconomic factors, comorbid conditions, and admission type.', 'Uninsured and Medicaid patients were found to have more emergent admissions and more comorbid disease compared with patients with private health insurance. Patients without private health insurance had higher rates of postoperative complications and in-hospital death compared with those patients with private insurance. After adjusting for patient and hospital characteristics, patients with Medicaid were found to be 22% more likely to develop a complication during their hospital admission (odds ratio [OR] of 1.22; 95% confidence interval [95%CI], 1.06-1.40) and 57% more likely to die postoperatively (OR of 1.57; 95% CI, 1.01-2.42) compared with patients with private insurance.']
['Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS).', 'The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures.', 'Indications for surgery were recurrent incisional hernia in 33\xa0% of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348\xa0cm(2) (±214; range 113-1,036) was used. Mean operative time was 132\xa0min (±66.1; range 53-412). The mean LOS was 4.0\xa0days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5\xa0% and no mortality. There was one recurrence in 30\xa0days (1.1\xa0%). Patients who had a surgery >120\xa0min or a LOS >1\xa0day were statistically more likely to have multiple hernias, larger defect sizes (>40\xa0cm(2)), larger mesh sizes (>300\xa0cm(2)) or a history of recurrent hernia (P\xa0<\xa00.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS.']
['Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs.', 'Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up.', 'A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups.']
['Novel immunosuppressives neither prevent nor attenuate post-transplant glomerulonephritis, third common cause of late allograft loss. Data addressing influence of ACEI/ARA and statins on kidney transplants survival is contradictory. The aim of this study was to evaluate efficacy of therapeutic interventions undertaken in post-transplant glomerulonephritis.', 'In 75 individuals with biopsy-confirmed post-transplant glomerulonephritis, engrafted in Warsaw Transplantation Institute, graft survival from index biopsy to permanent dialysis need, in regard to numerous therapeutic interventions was analysed. Evaluation of graft survival was performed using Kaplan-Meier estimator, log-rank and Wilcoxon tests. Relations between introduced treatment and time to graft loss was expressed with hazard ratio (HR), results regarded significant at p<0.05.', 'Glomerulonephritis diagnosis was established 50.2+/-39.5 months after engraftment. Maintenance immunosuppression modifications included: methylprednisolone infusions (n=28), cyclofosfamide/ chlorambucil introduction (n=10), mycophenolate mofetil addition to maintenance treatment (n=23). Immunosuppression modifications did not result in graft survival prolongation. Statins (n=20) and renin-angiotensin-system blockers (n=49) substantially diminished the risk of graft loss (respectively: HR=0.37 (95% CI 0.15-0.88), p<0.02. and HR=0.39 (95% CI 0.16-0.98; p<0.05). The effect persisted after adjustment for presentation with nephrotic syndrome, graft dysfunction, mean arterial pressure, immunosuppression enhancement with mycophenoalte mofetil. Best result was obtained with combined RAASB and statin treatment (HR=0.24; 95% CI 0.69-0.09, p=0.008).']
['Anti-smoking PSAs are not always effective in reducing cigarette smoking, and there is a lack of research into mechanisms through which PSAs affect the attitudes and behaviors of viewers. The present research was designed to better understand how smokers and non-smokers process anti-smoking ads.', "In a repeated measures design, the accessibility of smokers' (N = 70) and non-smokers' (N = 96) attitudes toward and norms concerning smoking were assessed and then their reactions to four anti-smoking PSAs were measured.", "The accessibility of smokers' attitudes toward smoking-how quickly they bring their attitudes to mind-predicted their central processing of ad content, and smokers who counterargued in response to the ads were not persuaded by them. The accessibility of smokers' norms for smoking-how quickly they bring to mind social support for smoking-predicted their peripheral processing of the ads, and imbued resistance to persuasion. In contrast, non-smokers' attitude and norm accessibility were unrelated to ad processing."]
['Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears.', 'Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears.', 'By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement.']
['To investigate subclinical atherosclerosis and the effect of treatment in patients with early rheumatoid arthritis (RA).', 'Forty patients with early RA who met the revised American College of Rheumatology (ACR) criteria and disease duration of <1 year were included in the study. Smokers and patients with classical risk factors for atherosclerosis were excluded. The serum levels of total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were determined in all patients before and after 1 year of therapy. Carotid artery intima-media thickness (IMT) and carotid plaque were measured before and after treatment. RA disease activity was measured using the 28 joint indices score (DAS-28) and clinical improvement was determined by the ACR response criteria. Forty-five age- and sex-matched nonsmoking volunteers were used as controls. All patients were treated with methotrexate and prednisone.', 'RA patients had a baseline mild dyslipidemia characterized by a decrease in serum HDL-C levels and a high TC/HDL-C atherogenic ratio compared with controls. Both lipid parameters were significantly improved after treatment (P<0.01). Common carotid artery IMTs at baseline were higher in RA patients compared with controls (P<0.05). After 1 year of therapy there was a significant decrease in the IMTs (P<0.001). Thirty-five patients (88%) achieved the ACR 20%, while 30 (75%) reached the ACR 50% response criteria. A significant decrease of DAS-28 was observed after treatment (P<0.03).']
["Decision making regarding the choice of surgical procedure in rectal cancer is complex. It was hypothesized that, in addition to clinical factors, several aspects of patients' socioeconomic background influence this process.", 'Individually attained data on civil status, education and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (16 713 patients) and analysed by logistic regression.', "Anterior resection (AR) was performed in 7433 patients (44.5 per cent), abdominoperineal resection (APR) in 3808 (22.8 per cent) and Hartmann's procedure in 1704 (10.2 per cent). Unmarried patients were least likely (odds ratio (OR) 0.76, 95 per cent confidence interval (c.i.) 0.64 to 0.88) and university-educated men were most likely (OR 1.30, 1.04 to 1.62) to have an AR. Patients with the highest income were more likely to undergo AR (OR 0.80, 0.85 and 0.86 respectively for first, second and third income quartiles). Socioeconomic differences in the use of AR were smallest among the youngest patients. Unmarried patients were more likely (OR 1.21, 95 per cent c.i. 1.00 to 1.48) and university-educated patients less likely (OR 0.78, 95 per cent c.i. 0.63 to 0.98) to have an APR."]
['A fluorescent compound of lipofuscin, A2-E, has been shown to impair lysosomal function and to increase the intralysosomal pH of human retinal pigment epithelial (RPE) cells. This study addressed the phototoxic potential of A2-E on RPE cells.', 'A2-E accumulation was confirmed by fluorescence microscopy and fluorescence-activated cell sorter analysis. Acridine orange staining allowed assessment of lysosomal integrity and intralysosomal pH. Phototoxic properties of A2-E were determined by exposing A2-E-free and A2-E-fed RPE cell cultures to short-wavelength visible light and assessing cell viability and lysosomal integrity.', 'Intralysosomal accumulation of A2-E was confirmed. Acridine orange staining showed that the A2-E was located in the lysosomal compartment and induced an elevation of intralysosomal pH. Exposure of A2-E fed cells to light resulted in a significant loss of cell viability by 72 h which was not observed in either RPE cells maintained in the dark or A2-E-free cultures exposed to light. Toxicity was associated with a loss of lysosomal integrity.']
['The prognosis of small cell lung cancer (SCLC) is poor, and there has been very little progress in the medical treatment of SCLC in the past two decades. We investigated the potential of Janus-activated kinases (JAK) inhibitor, AZD1480, for treatment of SCLC in vitro and in vivo.', 'JAK1 and JAK2 were inhibited by AZD1480 or siRNAs, and the effect of inhibition of JAK gene family on SCLC cell viability was evaluated. The effect of AZD1480 on cell-cycle distribution and apoptosis induction was studied. Antitumor effects of AZD1480 in tumor xenografts were assessed.', 'AZD1480 significantly inhibited growth of six out of 13 SCLC cells with IC50s ranging from 0.73 to 3.08 μmol/L. Knocking down of JAK2 and JAK1 inhibited proliferation of Jak2-positive/Jak1-negative H82 cells and Jak1-positive/Jak2-negative GLC4 cells, respectively. Treatment of SCLC cells with AZD1480 for 24 hours resulted in an increase of 4N DNA content and histone 3 serine 10 phosphorylation, indicative of G2-M phase arrest. Moreover, SCLCs underwent apoptosis after AZD1480 treatment as exemplified by the downregulation of MCL1, the accumulation of cleaved caspase 3, cleaved PARP, and increase of annexin-V-positive cells. Finally, xenograft experiments showed that AZD1480 attenuated the growth of H82 and GLC4 tumors in mice, and we observed stronger apoptosis as well as decreased CD31-positive endothelial cells in H82 and GLC4 xenografts upon AZD1480 treatment.']
['To define the accuracy of multiparametric magnetic resonance imaging (MP-MRI) for identifying focal and established extracapsular extension (ECE) in various zones of the prostate.', 'Between 2010 and 2013, 342 patients underwent MP-MRI of the prostate (3T, no endorectal coil with axial perfusion and diffusion images). The findings of the images were reported as negative, suspicious, or positive for ECE by a single expert radiologist. Radical prostatectomy specimens were reviewed to confirm the size and the location of ECE and further defined as focal or established ECE. Established ECE included extension that was multifocal or involving more than 5 glands. The accuracy of MRI in localizing focal and established ECE to each zone of the prostate was determined. Regression analyses were performed to identify predictors of ECE.', 'We identified 112 patients who underwent prostate MP-MRI and radical prostatectomy. MRI findings considered suspicious or definite for ECE accurately predicted pathologic ECE (P<0.001). MP-MRI identified established ECE but not focal ECE. Sensitivity, specificity, positive predictive value, and negative predictive value of MP-MRI for established ECE were 70.7%, 90.6%, 57.1%, and 95.1%, respectively. MRI identified ECE to the left vs. right side as well as each zone of the prostate; however, sensitivity was lowest at the apex. On multivariate analysis, MRI was a significant predictor of ECE that was independent of prostate-specific antigen level, Gleason score, and clinical stage.']
['The tibial insertion of the posterior cruciate ligament (PCL) frequently becomes damaged when performing a tibial cut in a PCL-retaining total knee replacement (TKA). The aim of this study was to quantify the functional effect of this structural damage on the tensile strength and failure load.', 'Six paired knees from fresh-frozen cadaver specimens were used. All soft tissues but the PCL were removed. In the left-sided specimens, a classic tibial cut at a depth of 9 mm with 3° of posterior slope was made, while in the right-sided specimens, a bone block was left in front of the tibial PCL insertion. After cementing a tibial tray, the specimens were mounted in a loading frame in 60° of flexion. The femur was translated anteriorly at a constant velocity rate of 0.5 mm/s. Tensions in the PCL were measured continuously until failure occurred.', 'In one specimen, the tibial PCL insertion was completely removed by the tibial cut. In the other five paired specimens, the mean tensile strength of the PCL was 380.6 ± 154.7 N in the left-sided knees. In the right-sided knees, the mean tensile strength was 738.4 ± 166.7. The average right-to-left ratio was 2.2 ± 0.7 (p = 0.006).']
['Serum &amp; Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation.', 'Here, we report that treatment of endometrial epithelial cells with specific inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT activity pathway results in reciprocal activation of SGK1. Flushing of the uterine lumen of mice with a cell permeable, substrate competitive phosphatidylinositol analogue that inhibits AKT activation (AKT inhibitor III) resulted in Sgk1 phosphorylation, down-regulation of the E3 ubiquitin-protein ligase Nedd4-2, and increased expression of epithelial Na+ channels (ENaC). Furthermore, exposure of the uterine lumen to AKT inhibitor III prior to embryo transfer induced a spectrum of early pregnancy defects, ranging from implantation failure to aberrant spacing of implantation sites.']
['To analyze the immunohistochemical expression of the standard isoform of CD44 (CD44s) adhesion molecule in clear cell renal cell carcinoma (CCRCC) and its impact on clinical outcomes.', 'Ninety-nine consecutive patients treated surgically for RCC between 1992 and 2009 were selected. A single pathologist reviewed all cases to effect a uniform reclassification and determine the most representative tumor areas for construction of a tissue microarray. The same pathologist, who was blinded to the outcome of the cases, semi-quantitatively scored the staining intensity of CD44s in all specimens. The counting was done using the H-Score algorithm.', 'Of the 99 immunostained RCC specimens, 57(57.7 %) showed low expression, and 42(42.4 %) showed high expression levels of CD44s. The expression of CD44s was directly associated with tumor size (p = 0.03), clinical stage (p = 0.02) and Fuhrman grade (p = 0.02). Disease specifi c survival (DSS) rates for patients whose specimens expressed low and high levels of CD44s was 88.1 % and 67.5 %, respectively (p = 0.009). Progression free survival (PFS) rates in patients with low and high expression of CD44s were 78.8 % and 61.7 %, respectively (p = 0.05). Classical features such as the presence of metastasis and clinical stage remained isolated predictors of survival.']
['\u2002 Small-for-size liver transplantation (SFSLT) often results in hepatic graft failure and decreased survival. The present study was aimed to investigate the possible mechanism of hepatic graft failure in SFSLT in rats.', '\u2002 Rat models of full-size orthotopic liver transplantation, 50% partial liver transplantation and 30% partial liver transplantation were established. Proliferative responses of the hepatic graft were evaluated by immunohistochemical staining and western blotting. Apoptosis-, inflammatory-, anti-inflammatory- and growth factor-related genes were screened by quantitative reverse transcription polymerase chain reaction. Activities of transcription factors of AP-1 and nuclear factor (NF)-κB were analyzed by electrophoretic mobility shift assay.', '\u2002 A 30% partial liver transplant not only resulted in marked structural damages to the hepatic graft, but also showed the lowest 7-day survival rate. In addition, sup pressed expressions of proliferating cell nuclear antigen (PCNA) and cyclin D1 by immunohistochemical staining and decreased expressions of cyclin D1 and p-c-Jun by western blotting were detected. Downregulated expressions of Bcl-2, Bcl-XL, interleukin (IL)-6, IL-10, IP-10 and CXCR2, upregulated expression of tumor necrosis factor-α, and decreased levels of AP-1 and NF-κB were also found following 30% partial liver transplantation after reperfusion.']
['Cell proliferation and cell cycle control mechanisms are thought to play central roles in the pathogenesis of atherosclerosis. The transcription factor Zinc finger protein 148 (Zfp148) was shown recently to maintain cell proliferation under oxidative conditions by suppressing p53, a checkpoint protein that arrests proliferation in response to various stressors. It is established that inactivation of p53 accelerates atherosclerosis, but whether increased p53 activation confers protection against the disease remains to be determined.', 'We aimed to test the hypothesis that Zfp148 deficiency reduces atherosclerosis by unleashing p53 activity.', 'Mice harboring a gene-trap mutation in the Zfp148 locus (Zfp148(gt/+)) were bred onto the apolipoprotein E (Apoe)(-/-) genetic background and fed a high-fat or chow diet. Loss of 1 copy of Zfp148 markedly reduced atherosclerosis without affecting lipid metabolism. Bone marrow transplantation experiments revealed that the effector cell is of hematopoietic origin. Peritoneal macrophages and atherosclerotic lesions from Zfp148(gt/+)Apoe(-/-) mice showed increased levels of phosphorylated p53 compared with controls, and atherosclerotic lesions contained fewer proliferating macrophages. Zfp148(gt/+)Apoe(-/-) mice were further crossed with p53-null mice (Trp53(-/-) [the gene encoding p53]). There was no difference in atherosclerosis between Zfp148(gt/+)Apoe(-/-) mice and controls on a Trp53(+/-) genetic background, and there was no difference in levels of phosphorylated p53 or cell proliferation.']
['Identification of historic pathogens is challenging since false positives and negatives are a serious risk. Environmental non-pathogenic contaminants are ubiquitous. Furthermore, public genetic databases contain limited information regarding these species. High-throughput sequencing may help reliably detect and identify historic pathogens.', "We shotgun-sequenced 8 16th-century Mixtec individuals from the site of Teposcolula Yucundaa (Oaxaca, Mexico) who are reported to have died from the huey cocoliztli ('Great Pestilence' in Nahautl), an unknown disease that decimated native Mexican populations during the Spanish colonial period, in order to identify the pathogen. Comparison of these sequences with those deriving from the surrounding soil and from 4 precontact individuals from the site found a wide variety of contaminant organisms that confounded analyses. Without the comparative sequence data from the precontact individuals and soil, false positives for Yersinia pestis and rickettsiosis could have been reported."]
['The optimal management of cholelithiasis after heart transplant remains unclear. We use expectant management based on symptoms, without screening studies or prophylactic treatment. We hypothesized that expectant management for cholelithiasis after heart transplant does not result in significant mortality or morbidity from gallstone-associated disease.', 'Between November 1985 and August 2004, 409 heart transplants were performed in 402 recipients at the University of Washington. This is a non-concurrent cohort study of these recipients.', 'Among recipients, 24 underwent cholecystectomy before heart transplant. After transplant, in the remaining 378 patients, 34 were found to have gallstones during the observation period. There was no mortality from gallstone-associated disease. Thirty patients developed morbidity from gallstones, including 25 cases of biliary colic, 3 of acute cholecystitis and 2 of pancreatitis, and there was 1 abnormal liver function test. Acute cholecystitis and pancreatitis were treated with conservative management followed by cholecystectomy. Cholecystectomy was performed in 32 patients after transplant. Indications included symptomatic cholelithiasis in 31, and prophylactic cholecystectomy prior to kidney transplant in 1. The laparoscopic approach was performed in 25 of these 32 patients. There was no mortality from cholecystectomy, but there were 4 complications: surgical site infections (n = 2); wound dehiscence (n = 1); and bile duct injury (n = 1). Median hospital stay was 1 day.']
['Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy.', 'A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed.', 'Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (≤ 4) (P = 0.01). Age ≤ 65, NLR >4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012).']
['To compare the long-term prognostic value of troponins (Tn) vs. conventional cardiac biomarker creatine kinase (CK) and CK-MB across the spectrum of acute coronary syndromes (ACS).', 'In the prospective, observational Canadian ACS Registry, 4627 patients with ACS were enrolled from 51 centres. The CK, CK-MB, Tn samples were analysed in each hospital clinical laboratory and the results related to the reference levels of the individual laboratories. The study cohort comprised 3138 (67.8%) patients who had both CK (or CK-MB) and Tn measurements during the first 24 h of hospitalisation. Vital status at one-year was determined by standardized telephone interview. 61.2% and 59.0% of patients had abnormal Tn and CK (or CK-MB) levels, respectively. Vital status at one-year was ascertained for 2950 patients (6% lost to follow-up). Among patients with normal CK (or CK-MB) levels, elevated Tn was associated with increased one-year mortality (odds ratio [OR] 2.06; 95% CI 1.37-3.11; P=0.001). Similarly, among patients with abnormal CK (or CK-MB) levels, abnormal Tn predicted higher one-year mortality (OR 1.83; 95% CI 1.14-2.93; P=0.01). In contrast, abnormal CK (or CK-MB) was not predictive of mortality after stratification by Tn status. In multivariable analysis controlling for other known prognosticators including creatinine, abnormal Tn (adjusted OR 1.78; 95% CI 1.30-2.44; P<0.001) but not CK/CK-MB was independently associated with increased one-year mortality.']
['The effects of dietary l-arginine (Arg) on immunosuppression following infectious bursal disease virus (IBDV) inoculation in broiler chickens were evaluated. The design of this study was a 5 × 2 factorial arrangement (n = 5) with five Arg concentrations (starter: 9.9, 13.9, 17.6, 21.3 and 25.3 g kg(-1) ; grower-finisher: 9.5, 13.5, 17.1, 20.1 and 23.6 g kg(-1) ) with or without IBDV inoculation (IBDV or saline inoculation at 14 days). Chickens were sampled at 2, 4 and 6 days post-inoculation (DPI) and 42 days of age.', 'The IBDV inoculation decreased (P = 0.05) CD3(+) , CD4(+) , and CD8(+) T cell counts at 2 days post-inoculation (DPI) and monocyte counts at 6 DPI; and reduced (P < 0.05) bursal interleukin-1β (IL-1β) mRNA expression at 2 DPI and serum IL-6 concentration at 4 DPI. Increasing Arg concentration increased (P < 0.05) CD4(+) and CD8(+) T cell counts at 2 DPI, linearly increased (P = 0.05) CD3(+) T cell counts in IBDV-inoculated groups and monocyte counts in control groups at 4 DPI; increased (P < 0.05) serum IL-6 concentration in IBDV-inoculated groups at 2 DPI; and increased (P < 0.05) serum anti-IBDV antibody titres at 42 days of age.']
['Effective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs), which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII).', 'Female 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis.', "The histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer's patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells."]
['Meningococcal meningitis is a major health problem in the "African Meningitis Belt" where recurrent epidemics occur during the hot, dry season. In Niger, a central country belonging to the Meningitis Belt, reported meningitis cases varied between 1,000 and 13,000 from 2003 to 2009, with a case-fatality rate of 5-15%.', "In order to gain insight in the epidemiology of meningococcal meningitis in Niger and to improve control strategies, the emergence of the epidemics and their diffusion patterns at a fine spatial scale have been investigated. A statistical analysis of the spatio-temporal distribution of confirmed meningococcal meningitis cases was performed between 2002 and 2009, based on health centre catchment areas (HCCAs) as spatial units. Anselin's local Moran's I test for spatial autocorrelation and Kulldorff's spatial scan statistic were used to identify spatial and spatio-temporal clusters of cases. Spatial clusters were detected every year and most frequently occurred within nine southern districts. Clusters most often encompassed few HCCAs within a district, without expanding to the entire district. Besides, strong intra-district heterogeneity and inter-annual variability in the spatio-temporal epidemic patterns were observed. To further investigate the benefit of using a finer spatial scale for surveillance and disease control, we compared timeliness of epidemic detection at the HCCA level versus district level and showed that a decision based on threshold estimated at the HCCA level may lead to earlier detection of outbreaks."]
['Smooth muscle cells (SMC) of the bladder undergo hypertrophy and hyperplasia following exposure to sustained mechanical overload. Although superficial similarities in the response of the heart and bladder to hypertrophic stimuli suggest that similar molecular mechanisms may be involved, this remains to be demonstrated. In this study we compared signal transduction pathway activation in primary culture bladder SMC and cardiac myofibroblasts in response to cyclic stretch. The effects of growth factor stimulation on pathway activation in bladder SMC were also investigated.', 'Primary culture rodent bladder SMC or cardiac myofibroblasts were subjected to cyclic stretch-relaxation in the absence or presence of pharmacologic inhibitors of the phosphoinositide-3-kinase, (PI3K)/Akt, extracellular signal-regulated kinase-mitogen activated protein kinase (Erk-MAPK) or the p38 stress-activated protein kinase-2 (SAPK2) pathways. In parallel experiments human bladder SMC were treated with platelet-derived growth factor-BB (PDGF-BB), heparin-binding EGF-like growth factor (HB-EGF) or fibroblast growth factor-2 (FGF-2). In each case the extent of DNA synthesis was determined by uptake of tritiated thymidine, and activation of specific signaling intermediates was determined by immunoblot analysis using antibodies to the non-phosphorylated and phosphorylated (activated) forms of Akt, p38 and Erk1/2.', 'Akt and p38 were rapidly phosphorylated in stretched bladder SMC and cardiac myofibroblasts, and stretch-induced DNA synthesis in these cells was ablated with inhibitors of PI3K or p38 but not Erk-MAPK. Similarly, PDGF-BB up-regulated DNA synthesis in bladder SMC in a p38 and Akt-dependent manner.']
['Stage II rectal cancers comprise a heterogeneous group, and there is significant variability in practise with regards to adjuvant chemotherapy; the survival benefit of chemotherapy is perceived to be <4% in these patients. However, in recent years, the emergence of additional prognostic factors such as extramural venous invasion (EMVI) suggests that there may be sub-stratification of stage II tumours and, further, we may be under-estimating the benefit adjuvant chemotherapy provides in high-risk patients. This study examined the outcomes of patients with stage II and III rectal cancer to determine whether EMVI status influences disease-free survival (DFS).', 'An analysis of a prospectively maintained database was conducted of patients presenting with rectal cancer between 2006 and 2012. All patients underwent curative surgery and had no evidence of metastases at presentation. Clinicopathological factors were compared between stage II and III disease. The primary end point was 3-year DFS; univariate and multivariate analysis was carried out using Cox proportional hazards regression models; hazard ratios (HR) with 95% confidence intervals (CIs) were calculated.', 'Four hundred and seventy-eight patients were included: 233 stage II; 245 stage III. The prevalence of EMVI was 34.9%; 57 stage II patients (24.5%) and 110 stage III patients (44.9%). On multivariate analysis, only EMVI status was a significant factor for DFS. The adjusted HR for EMVI either alone or in combination with nodal involvement was 2.08 (95% CI 1.10-2.95) and 2.74 (95% CI 1.66-4.52), respectively.']
['Infection with Helicobacter pylori is the main risk factor for development of gastric cancer. CD44 overexpression, especially that of variant 9 (CD44v9), has also been implicated in the local inflammatory response and metaplasia-carcinoma sequence in human stomach. We recently identified miR-328 as one of the microRNAs targeting CD44 in gastric cancer. The aim of the current study was to determine the relationship between miR-328 and CD44v9 expression in H. pylori-infected gastric mucosa during the development of preneoplastic lesions.', 'Immunohistochemical staining of myeloperoxidase and CD44v9 was performed using paraffin-embedded tissue sections obtained from 54 patients who underwent gastric resection without preoperative treatment. The levels of miR-328 expression in the gastric mucosa were measured in the same patients using quantitative reverse transcription polymerase chain reaction.', 'Both infiltration of myeloperoxidase-positive inflammatory cells and expression of proinflammatory cytokines closely correlated with H. pylori infection in the cancer-afflicted gastric mucosa. High CD44v9 expression levels, identified in the gastric mucosa in 61 % of samples (33/54), correlated significantly with H. pylori infection in the gastric mucosa. Notably, high CD44v9 expression was significantly associated with low miR-328 expression, whereas low CD44v9 expression was significantly associated with high miR-328 expression.']
['It can be clinically difficult to distinguish depressed individuals with bipolar disorder (BD) and major depressive disorder (MDD). To examine potential biomarkers of difference between the two disorders, the current study examined differences in the functioning of emotion-processing neural regions during a dynamic emotional faces task.', 'During functional magnetic resonance imaging, healthy control adults (HC) (n\xa0=\xa029) and depressed adults with MDD (n\xa0=\xa030) and BD (n\xa0=\xa022) performed an implicit emotional-faces task in which they identified a color label superimposed on neutral faces that dynamically morphed into one of four emotional faces (angry, fearful, sad, happy). We compared neural activation between the groups in an amygdala region-of-interest and at the whole-brain level.', 'Adults with MDD showed significantly greater activity than adults with BD in the left amygdala to the anger condition (p\xa0=\xa00.01). Results of whole-brain analyses (at p\xa0<\xa00.005, k\xa0≥\xa020) revealed that adults with BD showed greater activity to sad faces in temporoparietal regions, primarily in the left hemisphere, whereas individuals with MDD demonstrated greater activity than those with BD to displays of anger, fear, and happiness. Many of the observed BD-MDD differences represented abnormalities in functioning compared to HC.']
["To develop a theoretically informed and empirically validated survey instrument for assessing prescribers' perception of computerized drug-drug interaction (DDI) alerts.", "The survey is grounded in the unified theory of acceptance and use of technology and an adapted accident causation model. Development of the instrument was also informed by a review of the extant literature on prescribers' attitude toward computerized medication safety alerts and common prescriber-provided reasons for overriding. To refine and validate the survey, we conducted a two-stage empirical validation study consisting of a pretest with a panel of domain experts followed by a field test among all eligible prescribers at our institution.", 'The resulting survey instrument contains 28 questionnaire items assessing six theoretical dimensions: performance expectancy, effort expectancy, social influence, facilitating conditions, perceived fatigue, and perceived use behavior. Satisfactory results were obtained from the field validation; however, a few potential issues were also identified. We analyzed these issues accordingly and the results led to the final survey instrument as well as usage recommendations.']
['It has been shown that the expression of the receptor for advanced glycation end products (RAGE) is closely associated with invasion and metastasis in gastric cancer. A Gly82Ser polymorphism in exon 3 of RAGE gene was identified and thought to have an effect on the functions of its protein. Therefore, the goal of the present study was to investigate whether the polymorphism is involved in the development or progression of gastric cancer.', 'In the hospital-based case-control study, the RAGE genotypes were determined using PCR-RFLP in 566 individuals (283 gastric cancer patients and 283 age- and sex-matched controls).', 'The distribution of genotype was significantly different between cases and controls (P = 0.038). Compared with the wild-type 82Gly/Gly carriers, subjects with the variant genotypes (82Gly/Ser and 82Ser/Ser) had a significantly higher risk of gastric cancer (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Moreover, the elevated gastric cancer risk was especially evident in younger individuals (ages < or =58 years), nonsmokers, and rural subjects. Further analyses revealed that the variant genotypes were associated with adjacent organ invasion in the subanalysis of gastric cancer patients.']