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['Heterozygous ATP-binding-cassette subfamily A member 3 (ABCA3) mutations are associated with neonatal respiratory complications. In an adult murine model, we investigated whether Abca3 haploinsufficiency is a predisposing factor for lung injury induced by hyperoxia or mechanical ventilation.', 'Abca3 haploinsufficient (Abca3(+/-)) and wild-type (WT) mice were prospectively randomized to 25 min of ventilation or 72 h of hyperoxia or left unchallenged in air.', 'As compared with WT mice, unchallenged Abca3(+/-) mice had significantly decreased lung phosphatidylcholine (PC) and phosphatidylglycerol (PG) levels (P < 0.02) and decreased lung compliance (P < 0.05). When ventilated for 25 min, Abca3(+/-) mice demonstrated a significantly greater increase in bronchoalveolar lavage (BAL) interleukins (P ≤ 0.01) and lung wet to dry ratio (P < 0.005). Hyperoxia resulted in increased compliance (P < 0.05) and total lung capacity (TLC) (P = 0.01) only in the Abca3(+/-) mice, consistent with enlarged alveolar spaces. The ratio of PC to PG in BAL-relevant for surfactant dysfunction-was significantly elevated by oxygen exposure, with the greatest increase in Abca3(+/-) mice.']
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['The T-cell antigen receptor (TCR) has been reported to be down-regulated on T-cells in the decidualized endometrium in early pregnancy.', 'The expression of CD3zeta, a component of the TCR complex, has been investigated in human first-trimester decidual T-cells using flow cytometric analysis of permeabilized cells.', 'Levels of CD3zeta expression were significantly lower in decidual than in peripheral T-cells from non-pregnant women, as assessed by mean fluorescence intensity (4.2 vs. 5.5, logarithmic scale, P < 0.05). However, when decidual and peripheral T-cells from the same subjects were analyzed (n = 10), mean levels of CD3zeta were slightly, but not significantly, lower in decidual than in peripheral T-cells (P > 0.1). CD3zeta was not substantially down-regulated systemically as mean cytoplasmic CD3zeta levels did not differ significantly between peripheral blood T-cells from pregnant women and non-pregnant controls (P > 0.2). CD8+ cells outnumber CD4+ cells in decidua, but neither the proportions of these two T-cell subsets positive for cytoplasmic CD3zeta nor the mean levels of CD3zeta were significantly different.']
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['Measurement of motor cortex excitability with single and paired pulse transcranial magnetic stimulation has become an established method for in vivo characterization of the effects of central-acting drugs. The comparison of drug-free and medicated patients with schizophrenia suggests an association of neuroleptics intake and prolongation of the cortical silent period (CSP). However all available data come from cross-sectional non-randomized studies. Thus it is not clear whether the observed difference is an effect of medication or reflects differences in disease severity or both.', 'We aimed to investigate whether the CSP or other parameters of cortical excitability change, when cortical excitability is measured in drug-free patients with acute psychosis before and after 3week intake of the atypical neuroleptic quetiapine.', 'Different parameters of cortical excitability were studied in 24 drug-free patients with acute psychosis before and after 3weeks of treatment with a mean dose of 352±199mg quetiapine.', 'We observed a significant prolongation of the cortical silent period (CSP) after three week treatment with quetiapine. Other parameters of cortical excitability such as motor threshold (MT), short intracortical inhibition (SICI) and intracortical facilitation (ICF) remained unaffected. There was a significant improvement in clinical parameters (PANS, GAF) but no significant correlation between clinical improvement and changes in cortical excitability.']
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['LKB1 loss is common in lung cancer, but no assay exists to efficiently evaluate the presence or absence of LKB1. We validated an IHC assay for LKB1 loss and determined the impact of LKB1 loss in KRAS-mutant non-small cell lung cancer (NSCLC).', 'We optimized and validated an IHC assay for LKB1 (clone Ley37D/G6) using a panel of lung cancer cell lines and tumors with known LKB1 mutations, including 2 patients with Peutz-Jeghers syndrome (PJS) who developed lung adenocarcinoma. We retrospectively analyzed tumors for LKB1 using IHC from 154 KRAS-mutant NSCLC patients, including 123 smokers and 31 never-smokers, and correlated the findings with patient and tumor characteristics and clinical outcome.', 'LKB1 expression was lost by IHC in 30% of KRAS-mutant NSCLC (smokers 35% vs. never-smokers 13%, P = 0.017). LKB1 loss did not correlate with a specific KRAS mutation but was more frequent in tumors with KRAS transversion mutations (P = 0.029). KRAS-mutant NSCLC patients with concurrent LKB1 loss had a higher number of metastatic sites at the time of diagnosis (median 2.5 vs. 2, P = 0.01), higher incidence of extrathoracic metastases (P = 0.01), and developed brain metastasis more frequently (48% vs. 25%, P = 0.02). There was a nonsignificant trend to worse survival in stage IV KRAS-mutant NSCLC patients with LKB1 loss.']
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['The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified.', 'To examine the association between self-reported family history of skin cancer and SCC risk.', 'Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors.', 'Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6).']
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['Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion.', 'The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamide v placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent.', 'Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTPD (20.2 (0.5)/16.3 (0.5) and in CTLD (16.0 (0.5)/12.3 (0.5)) was highly significantly (p < 0.001) reduced and was significantly (p < 0.03) reduced in vehicle (V) treated eyes (HTPv: 20.3 (0.4)/19.0 (0.4)) and CTLv: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTPD (2.1 (0.1)/2.5 (0.1)) and CTLD (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p < 0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged.']
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['Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC) significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects.', 'In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 +/- 3.6 years) participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL), in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP) and mean values (MP) of sprint power output and percent decrement of power (DEC) were determined per bout and standardized relative to body masss. Heart rate (HR) and blood lactate (LAC) were measured prior to, during and following the five sprint bouts.', 'Significant main effects (p < 0.001) were observed for sprint bout order in values of PP, MP, DEC, and HR. There were significant main effects detected for condition in PP and MP (p < 0.05), with values across the five sprint bouts 2.6 - 15% greater with GPLC. Significant statistical interactions were detected between bout order and condition for both PP and MP (p < 0.05). There was a significant main effect of condition for LAC, LAC values 15.7% lower 4 min post-exercise with GPLC (p = 0.09) and with GPLC resulting in 16.2% less LAC at 14 min post-exercise (p < 0.05).']
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['Beckwith-Wiedemann syndrome (BWS) is a loss-of-imprinting pediatric overgrowth syndrome. The primary features of BWS include macrosomia, macroglossia, and abdominal wall defects. Secondary features that are frequently observed in BWS patients are hypoglycemia, nevus flammeus, polyhydramnios, visceromegaly, hemihyperplasia, cardiac malformations, and difficulty breathing. BWS is speculated to occur primarily as the result of the misregulation of imprinted genes associated with two clusters on chromosome 11p15.5, namely the KvDMR1 and H19/IGF2. A similar overgrowth phenotype is observed in bovine and ovine as a result of embryo culture. In ruminants this syndrome is known as large offspring syndrome (LOS). The phenotypes associated with LOS are increased birth weight, visceromegaly, skeletal defects, hypoglycemia, polyhydramnios, and breathing difficulties. Even though phenotypic similarities exist between the two syndromes, whether the two syndromes are epigenetically similar is unknown. In this study we use control Bos taurus indicus X Bos taurus taurus F1 hybrid bovine concepti to characterize baseline imprinted gene expression and DNA methylation status of imprinted domains known to be misregulated in BWS. This work is intended to be the first step in a series of experiments aimed at determining if LOS will serve as an appropriate animal model to study BWS.', 'The use of F1 B. t. indicus x B. t. taurus tissues provided us with a tool to unequivocally determine imprinted status of the regions of interest in our study. We found that imprinting is conserved between the bovine and human in imprinted genes known to be associated with BWS. KCNQ1OT1 and PLAGL1 were paternally-expressed while CDKN1C and H19 were maternally-expressed in B. t. indicus x B. t. taurus F1 concepti. We also show that in bovids, differential methylation exists at the KvDMR1 and H19/IGF2 ICRs.']
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['The involvement of nephrin in controlling renal function is unclear with the literature only emphasizing its role in albuminuria. We therefore investigated the potential association between nephrinuria as evidenced by the appearance of urinary immunopositive nephrin fragments, with multiple renal traits.', 'Western blot analysis of the urine samples from a cross-sectional study of 381 Chinese type 2 diabetic patients revealed four distinct protein fragments, indicative of nephrinuria. Albuminuria was measured in random spot urine samples using the albumin/creatinine ratio (ACR), while estimated glomerular filtration rate (eGFR) was calculated using the creatinine-based Modification of Diet in Renal Disease formula.', 'Each nephrin fragment was associated with a decline in eGFR (smallest P = 0.001). Even with the inclusion of logarithmic form of ACR (ln ACR) in the multivariate model, nephrinuria still remained significantly associated with lower eGFR (smallest P < 0.05). Nephrinuria was also strongly associated with lnACR and this finding was independent of eGFR (smallest P < 0.001). Thus, nephrinuria was independently associated with both renal traits in the form of lnACR and eGFR. Furthermore, nephrinuria was significantly associated with lower eGFR even among normoalbuminuric patients (ACR ≤ 30 mg/g) (smallest P = 0.002), potentially implicating nephrinuria in the development of normoalbuminuric renal insufficiency. Apart from the renal traits under investigation, the presence of nephrinuria did not associate with other patient clinical characteristics.']
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['Our objective was to investigate whether pro-oxidant properties of ascorbic acid (AA) and tetrahydrobiopterin (BH(4)) modulate endothelium-dependent, electrotonically mediated arterial relaxation.', 'In studies with rabbit iliac artery (RIA) rings, NO-independent, endothelium-derived hyperpolarizing factor (EDHF)-type relaxations evoked by the sarcoplasmic endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid and the G protein-coupled agonist acetylcholine (ACh) were enhanced by AA (1 mM) and BH(4) (200 microM), which generated buffer concentrations of H(2)O(2) in the range of 40-80 microM. Exogenous H(2)O(2) potentiated cyclopiazonic acid (CPA)- and ACh-evoked relaxations with a threshold of 10-30 microM, and potentiation by AA and BH(4) was abolished by catalase, which destroyed H(2)O(2) generated by oxidation of these agents in the organ chamber. Adventitial application of H(2)O(2) also enhanced EDHF-type dilator responses evoked by CPA and ACh in RIA segments perfused intraluminally with H(2)O(2)-free buffer, albeit with reduced efficacy. In RIA rings, both control relaxations and their potentiation by H(2)O(2) were overcome by blockade of gap junctions by connexin-mimetic peptides (YDKSFPISHVR and SRPTEK) targeted to the first and second extracellular loops of the dominant vascular connexins expressed in the RIA. Superoxide dismutase attenuated the potentiation of EDHF-type relaxations by BH(4), but not AA, consistent with findings demonstrating a differential role for superoxide anions in the generation of H(2)O(2) by the two agents.']
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['Torcetrapib, a prototype cholesteryl ester transfer protein (CETP) inhibitor with potential for decreasing atherosclerotic disease, increased cardiovascular events in clinical trials. The identified hypertensive and aldosterone-elevating actions of torcetrapib may not fully account for this elevated cardiovascular risk. Therefore, we evaluated the effects of torcetrapib on endothelial mediated vasodilation in vivo.', "In vivo endothelial mediated vasodilation was assessed using ultrasound imaging of acetylcholine-induced changes in rabbit central ear artery diameter. Torcetrapib, in addition to producing hypertension and baseline vasoconstriction, markedly inhibited acetylcholine-induced vasodilation. A structurally distinct CETP inhibitor, JNJ-28545595, did not affect endothelial function despite producing similar degrees of CETP inhibition and high-density lipoprotein elevation. Nitroprusside normalized torcetrapib's basal vasoconstriction and elicited dose-dependent vasodilation of norepinephrine preconstricted arteries in torcetrapib-treated animals, indicating torcetrapib did not impair smooth muscle function."]
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['Abstract Aims: To investigate the effect of chloride intracellular channel 1 (CLIC1) on the proliferation, migration, and apoptosis of prostate cancer cell lines PC-3 and DU145 and the possible molecular mechanisms.', 'Using the technique of RNA interference, the expression of CLIC1 was downregulated in the PC-3 and DU145 cell lines. MTT assay, Transwell chamber, and flow cytometry were used to determine the effect of CLIC1 on the proliferation, migration, and apoptosis ability of PC-3 and DU145 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, matrix metalloproteinase (MMP)-2, and MMP-9 were examined by western blotting.', 'The results showed that the knockdown of CLIC1 exerts inhibitory effects on the proliferation and migration of PC-3 and DU145 cells. At the same time, the authors found that the knockdown of CLIC1 has no effect on the apoptosis in PC-3 and DU145 cells. Meanwhile, the levels of p-ERK1/2, MMP-2, and MMP-9 were decreased in the CLIC1 small interfering RNA (siRNA) group compared with the control and vector groups.']
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['Abdominal pain and discomfort are common symptoms in functional disorders and are attributed to visceral hypersensitivity. These symptoms fluctuate over time but the basis for this is unknown. Here we examine the impact of changes in gut flora and gut inflammatory cell activity on visceral sensitivity.', 'Visceral sensitivity to colorectal distension (CRD) was assessed at intervals in healthy mice for up to 12 weeks, and in mice before and after administration of dexamethasone or non-absorbable antibiotics with or without supplementation with Lactobacillus paracasei (NCC2461). Tissue was obtained for measurement of myeloperoxidase activity (MPO), histology, microbiota analysis, and substance P (SP) immunolabelling.', 'Visceral hypersensitivity developed over time in healthy mice maintained without sterile precautions. This was accompanied by a small increase in MPO activity. Dexamethasone treatment normalised MPO and CRD responses. Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity. Administration of Lactobacillus paracasei in spent culture medium normalised visceral sensitivity and SP immunolabelling, but not intestinal microbiota counts.']
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['Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs). CYP2C9-derived EETs elicit endothelial cell proliferation and angiogenesis, but the signaling pathways involved are incompletely understood. Because cyclooxygenase-2 (COX-2) is involved in angiogenesis, we determined whether a link exists between CYP2C9 and COX-2 expression.', 'Human umbilical vein endothelial cells were infected with CYP2C9 sense or antisense adenoviral constructs. Overexpression of CYP2C9 increased COX-2 promoter activity, an effect accompanied by a significant increase in COX-2 protein expression and elevated prostacyclin production. The CYP2C9-induced expression of COX-2 was inhibited by the CYP2C9 inhibitor, sulfaphenazole, whereas 11,12-EET increased COX-2 expression. Overexpression of CYP2C9 and stimulation with 11,12-EET increased intracellular cAMP levels and stimulated DNA-binding of the cAMP-response element-binding protein. The protein kinase A inhibitor, KT5720, attenuated the CYP2C9-induced increase in COX-2 promoter activity and protein expression. Overexpression of CYP2C9 stimulated endothelial tube formation, an effect that was attenuated by the COX-2 inhibitor celecoxib. Identical responses were observed in cells preconditioned by cyclic strain to increase CYP2C expression.']
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['To evaluate the adequacy of gestational weight gain and to determine its association with maternal socioeconomic, demographic and nutritional factors and health care, to estimate the prevalence of low birth weight, macrosomia, preterm birth and cesarean delivery and to identify the association of these outcomes with the adequacy of weight gain.', 'A cross-sectional study was performed in 2009/2010 to obtain socioeconomic, demographic, nutritional, dietary and physical activity data of pregnant women assisted by primary health care in a municipality of the state of São Paulo. Subsequently, data were collected from the medical records to evaluate gestational weight gain. Type of delivery, birth weight and gestational age at delivery were obtained from the Livebirths Information System. Gestational weight gain was evaluated according to the recommendations of the Institute of Medicine (2009). Associations were investigated by comparing the frequencies and by logistic regression, with excessive weight gain (yes, no) and insufficient gain (yes, no) being the dependent variables.', 'A total of 212 pregnant women were studied: 50.5% had excessive gain and 19.8% insufficient weight gain. Only prepregnancy nutritional status was associated with adequacy of weight gain: compared with normal weight, prepregnancy overweight women had a four-fold higher chance to gain excessive weight (OR 4.66, 95%CI 2.19-9.4). Nearly a third of babies were born by caesarian section, 5.7% were premature, 7.1% were underweight and 4.7% were macrosomic. There was no association between adequacy of gestational weight gain and these outcomes.']
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['Food addiction is a debated topic in neuroscience. Evidence suggests diabetes is related to reduced basal dopamine levels in the nucleus accumbens, similar to persons with drug addiction. It is unknown whether insulin sensitivity is related to endogenous dopamine levels in the ventral striatum of humans. We examined this using the agonist dopamine D2/3 receptor radiotracer [(11)C]-(+)-PHNO and an acute dopamine depletion challenge. In a separate sample of healthy persons, we examined whether dopamine depletion could alter insulin sensitivity.', 'Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. Eleven healthy nonobese and nondiabetic persons (3 female) provided a baseline [(11)C]-(+)-PHNO scan, 9 of which provided a scan under dopamine depletion, allowing estimates of endogenous dopamine at dopamine D2/3 receptor. Dopamine depletion was achieved via alpha-methyl-para-tyrosine (64mg/kg, P.O.). In 25 healthy persons (9 female), fasting plasma and glucose was acquired before and after dopamine depletion.', 'Endogenous dopamine at ventral striatum dopamine D2/3 receptor was positively correlated with insulin sensitivity (r(7)=.84, P=.005) and negatively correlated with insulin levels (r(7)=-.85, P=.004). Glucose levels were not correlated with endogenous dopamine at ventral striatum dopamine D2/3 receptor (r(7)=-.49, P=.18). Consistently, acute dopamine depletion in healthy persons significantly decreased insulin sensitivity (t(24)=2.82, P=.01), increased insulin levels (t(24)=-2.62, P=.01), and did not change glucose levels (t(24)=-0.93, P=.36).']
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['The cellular and molecular mechanisms that regulate the organization of bladder urothelium into basal, intermediate and superficial cell layers remain poorly understood. We tested the hypothesis that fibroblast growth factor (FGF)-7 is essential for generating a multilayered stratified bladder epithelium.', 'The morphological and molecular characteristics of bladder urothelium in age and sex matched FGF-7 +/+ wild-type and -/- null mice were evaluated. In addition, the effect of exogenous FGF-7 on the growth and differentiation of primary murine urothelial cells was assessed.', 'Morphometric analyses demonstrate that FGF-7 null urothelium is markedly thinned compared with wild-type urothelium. Electron microscopy revealed that null urothelium lacks the intermediate cell layers and molecular marker analyses confirmed this observation. In vitro cell culture experiments indicated that FGF-7 regulates urothelial cell growth, differentiation and stratification. Primary urothelial cultures maintained without FGF-7 ceased to divide and expressed proteins characteristic of terminally differentiated umbrella cells. In contrast, cultures maintained with exogenous FGF-7 contained proliferating epithelial cells with protein expression patterns consistent with those of intermediate cells in addition to terminally differentiated, post-mitotic umbrella cells. Importantly, isolated urothelial cells maintained with exogenous FGF-7 formed a multilayered epithelium in vitro.']
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['Conflicting results have been reported regarding the acute effects of triiodothyronine (T3) on myocardial contractile performance. The present study analyzes the role of T3 in reversing the depressant effect of excessive catecholamine stimulation in isolated porcine left ventricular myocardium.', 'Thirty-six left ventricular trabeculae (0.4 x 6.0 mm) obtained from 6 pigs were used for measurements of isometric force development, isotonic shortening, and intracellular calcium in three experimental series (measurement conditions: 37 degrees C; optimal length; supramaximal electrical stimulation, 1 Hz; calcium measurement, fura-2 ratio method; frequency, 225 Hz). In series 1, isometric force development was measured before and after a 60-minute incubation with 10(-7) mol/L epinephrine in preparations with (n = 6) and without (n = 6) preceding fura-2 loading for calcium measurements. In series 2, the acute effects of a 30-minute administration of T3 (10(-9) mol/L) on isometric force and intracellular calcium were analyzed (n = 6). In series 3, after simultaneous fura-2 loading and a 6-hour 10(-7) mol/L epinephrine exposure the effects of T3 (10(-9) mol/L, 30 minutes) on force development, shortening, and intracellular calcium transient were analyzed.', 'Long-term and high-dose epinephrine exposure induced a severe contractile depression with a significant reduction of isometric force development (p < 0.05) and increased diastolic (p < 0.001) and systolic calcium (p < 0.001). In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium. Triiodothyronine increased the shortening amplitude and the force amplitude (p < 0.01).']
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['The tumour necrosis factor (TNF)-2 promoter allele, which elicits elevated expression of TNF-alpha, is in linkage disequilibrium with the extended haplotype HLA-A1-B8-DR3-DQ2. TNF-2 and HLA-DR3 have been implicated in renal and cardiac graft rejection and loss. Cytomegalovirus (CMV) infection has been associated with chronic allograft rejection. We examined the relationship between HLA-DR3, promoter allele TNF-2 and cytomegalovirus in relation to chronic rejection following liver transplantation.', '(i) Retrospective analysis of HLA-DR3 was performed in 307 liver transplant recipients and 283 donors. (ii) Prospective analysis of TNF-alpha promoter allele status, HLA-DR3 status and cytomegalovirus infection was assessed in 123 recipients.', '(i) Retrospective analysis. Recipient HLA-DR3 (relative risk 1.9; 95% C.I. 1.01-3.58) was a risk factor for chronic rejection. (ii) Prospective analysis. Recipient HLA-DR3 was a risk factor for chronic rejection (relative risk 3.41; 95% C.I. 1.66-7.03) which was elevated further by superimposed CMV infection (relative risk 5.01; 95% C.I. 2-12.55). Recipient TNF-2 was associated with chronic rejection (relative risk 2.29; 95% C.I. 0.9-5.83) through linkage to HLA-DR3.']
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['We addressed the question whether the response of osteoporotic patients to bisphosphonate treatment is reduced with time. Bisphosphonate-treated women with postmenopausal or glucocorticoid-induced osteoporosis showed adequate and consistent changes of bone markers to subsequently administered intravenous pamidronate. Response of osteoporotic patients to bisphosphonates is not impaired during their long-term administration.', "Inadequate response to bisphosphonate treatment has been described in patients with Paget's disease of bone but has not been addressed in osteoporosis although treatment failure is a clinically relevant problem.", 'Twenty one women with postmenopausal osteoporosis (PMO) aged 68\u2009±\u20098.2 years and 14 women with glucocorticoid-induced osteoporosis (GIOP) aged 65\u2009±\u200910 years were treated with tri-monthly intravenous infusions of 45 mg of pamidronate for 1 year. All patients had been previously treated with bisphosphonates (alendronate, risedronate, pamidronate) for a mean period of 6.2 years (range, 1.3-14 years). Blood samples were taken for measurement of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) on days\u20091 and 4 and of the bone formation marker procollagen type I N propeptide, (P1NP) on day\u20091 of every tri-monthly treatment course.', 'With each treatment course there was a significant decrease in serum CTX-I on day\u20094 and an increase to baseline values 3 months after each infusion in both PMO (mean values, day\u20091: 291.33\u2009±\u2009160.78 pg/ml vs. day\u20094: 131\u2009±\u200991.7 pg/ml, p\u2009<\u20090.001) and GIOP (day\u20091: 219.3\u2009±\u2009114.8 pg/ml vs. day\u20094: 98.8\u2009±\u200951.6 pg/ml, p\u2009<\u20090.001). Serum P1NP remained stable during the whole year of treatment.']
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['To determine the validity of the diagnostic algorithms for osteoporosis and fractures in administrative data.', 'A systematic search was conducted to identify studies that reported the validity of a diagnostic algorithm for osteoporosis and/or fractures using administrative data.', 'Twelve studies were reviewed. The validity of the diagnosis of osteoporosis in administrative data was fair when at least 3 years of data from hospital and physician visit claims were used (area under the receiver operating characteristic [ROC] curve [AUC]=0.70) or when pharmacy data were used (with or without the use of hospital and physician visit claims data, AUC>0.70). Nonetheless, the positive predictive values (PPVs) were low (<0.60). There was good evidence to support the use of hospital data to identify hip fractures (sensitivity: 69-97%; PPV: 63-96%) and the addition of physician claims diagnostic and procedural codes to hospitalization diagnostic codes improved these characteristics (sensitivity: 83-97%; PPV: 86-98%). Vertebral fractures were difficult to identify using administrative data. There was some evidence to support the use of administrative data to define other fractures that do not require hospitalization.']
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['Elevated maternal serum levels of interleukin-2 soluble receptor-alpha (IL-2 sRalpha), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been associated with pregnancy loss. The aim of our study was to evaluate the predictive value of these cytokines in the outcome of early IVF pregnancies.', 'One hundred and fifty-nine consecutive IVF patients who were subsequently diagnosed to have a biochemical pregnancy (n = 23), a first-trimester miscarriage (n = 19) or a normal term delivery (n = 117) were included in this study. Serum was collected from the initial pregnancy test, 11 days after a day 3 embryo transfer, and all samples were analysed for IL-2 sRalpha, TNF-alpha and IFN-gamma by commercially available enzyme-linked immunosorbent assay (ELISA) kits.', "IL-2 sRalpha levels were significantly higher in patients with an early pregnancy loss compared with patients with a normal term delivery (849.5 +/- 69.6 versus 693.5 +/- 31.2 pg/ml, P = 0.02), and a cut-off point of IL-2 sRalpha >1000 pg/ml predicted a poor pregnancy outcome (44.4 versus 22.7% pregnancy loss, IL-2 sRalpha >or=1000 versus IL-2 sRalpha <1000 pg/ml; P = 0.02). IFN-gamma-positive patients had twice the risk for poor IVF pregnancy outcome compared with IFN-gamma-negative subjects (40.8 versus 20.0%, respectively; P < 0.02), including a significantly lower implantation rate (37.6 +/- 0.05 versus 50.0 +/- 0.03%, respectively; P = 0.02). There was no difference in pregnancy outcome based upon serum levels, or the ability to detect the presence of TNF-alpha. No differences in levels of these cytokines were found based on the aetiology of the patients' infertility."]
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['The aim of this study was to determine whether expression of the CD86 costimulatory molecule in acute myeloid leukemia (AML) can identify blast cells committed to the monocytic/dendritic lineage.', 'One hundred ten consecutive AML patients observed at diagnosis were studied by flow cytometry. In selected experiments, in vitro cultures with CD34(+)CD86(+) or CD34(-)CD86(+) blasts were performed in the presence of granulocyte-macrophage colony-stimulating actor (GM-CSF) with or without tumor necrosis factor-alpha (TNF-alpha) or GM-CSF + interleukin-4 (IL-4), respectively, to induce a dendritic differentiation, documented by morphologic and immunophenotypic assays. T-cell alloreactivity to CD86(+) AML cells and leukemic dendritic cells (AML-DC) was tested in mixed leukocyte cultures and anti-leukemic cytotoxic assays.', 'CD86 was expressed in 54% AML, whereas CD80 and CD1a were only occasionally positive. CD86(+) AML samples included M5 and M4, but also 47% M0-M1 FAB types, and were more frequently CD14(+) (p < 0.00001) and CD34(-) (p = 0.00005) than CD86(-)AML. Six different patterns of CD86(+) AML were identified, according to CD34 or CD14 total or partial coexpression. Four samples enriched in CD34(+)CD86(+) AML cells differentiated into AML-DC CD86(+), CD80(+), CD40(+), CD11c(+), HLA-DR(++), CD14(+/-) that also were CD1a(+) or CD83(+), after 6 days of in vitro culture with GM-CSF +/- TNF-alpha. CD34(-)CD86(+) AML cells differentiated into AML-DC after 3 to 5 days (n = 5 experiments), and trisomy 8 was found in two AML and AML-DC samples by fluorescence in situ hybridization analysis. Finally, AML-DC induced more potent allo-T-cell proliferation, cytokine release, and anti-leukemic cytotoxicity than CD86(+) blasts.']
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['To ascertain the incidence and to review the obstetric and neonatal correlates of placental haemosiderosis. Secondly, to determine if placental haemosiderosis is due to blood contamination during placental handling.', 'One hundred consecutive singleton placentas with and 113 consecutive singleton placentas from uncomplicated pregnancies without an indication for pathological examination were stained for iron to detect haemosiderosis in the membranes, chorionic plate and/or basal plate. The obstetric and neonatal data were analysed. In the second part, maternal retroplacental blood was placed on the chorionic plates of 15 placentas for 1, 3, 4 and 5 days prior to sampling and examination for iron deposition.', 'Haemosiderosis was observed in 110 of 213 (51.6%) placentas. Early decelerations during fetal heart rate monitoring (p = 0.0498) and, negatively, maternal thrombophilia (p = 0.0496) were related to haemosiderosis in the placenta. Preterm delivery, chronic separation of the placenta or procedures performed during pregnancy or delivery were not significantly related to haemosiderosis. Different patterns of iron staining were observed but these were not correlated with any maternal or neonatal factors. In the experimental study, haemosiderin was not found in sections taken at various time intervals from both blood contaminated and blood contamination-free parts of the placentas.']
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['To determine the roles of transforming growth factor-beta( 1) (TGF-beta(1)), epidermal growth factor (EGF), and cell density on the regulation of the TGFBI gene transcript in a human corneal epithelial cell line (HCE-T).', 'HCE-T cells (40-50% confluent), which possess the biochemical and morphological phenotype of human corneal epithelial cells, were treated with either TGF-beta(1) (20 ng/ml) or EGF (20 ng/ml) for 0, 24, 48, and 72 h. Total RNA was isolated at each time point from the treated cells and the placebo-treated controls. The TGFBI mRNA transcript level was quantitated using Northern blot analysis.', 'TGF-beta(1) upregulates TGFBI gene transcript in this human corneal epithelial cell line, reaching a peak of 2.5-fold of upregulation at 48 h after TGF-beta(1) treatment and a 1.5-fold at 72 h. In contrast, EGF treatment showed no effect on the TGFBI mRNA level. In addition, the TGFBI gene transcript appears to be cell density-dependent because the transcript level shows a trend of reduction as the cell density increases from 40-50% to full confluency.']
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['Acute ischemic diseases of the small bowel are lethal emergencies with no reliable diagnostic biochemical tests available. Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel.', 'Enzyme immunoassay was applied to determine I-FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized patients with acute abdominal pain.', 'Serum I-FABP levels were < 65 ng/mL in healthy subjects. In patients with acute abdominal pain, levels ranged from < 20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in healthy subjects. However, patients with ischemic bowel disease showed significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8 ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL.']
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['To address the question of whether the high levels of oxidative modified low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum of healthy women throughout gestation.', 'Blood was taken from 33 patients at four different time points from early to late gestation and post-partum. OxLDL and anti-oxLDL concentrations were measured by enzyme-linked immunosorbent assays. ANOVA was used for statistical evaluations followed by post hoc test with Bonferoni adjustment.', 'Oxidized Low Density Lipoprotein concentrations increased while anti-oxLDL levels decreased significantly from early to late gestation. OxLDL was strongly positively correlated with LDL concentration and mildly negatively associated with anti-oxLDL levels. Estimating the status of oxidation by calculating oxLDL/LDL ratio revealed decreasing values with ongoing pregnancy. Multivariate analysis showed that anti-oxLDL levels were dependent on gestational age but neither on oxLDL levels nor on the oxLDL/LDL ratio.']
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['Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery.', "Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients' medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography.", 'Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (α) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751.']
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["Arterial stiffness is an independent determinant of cardiovascular risk, and there is evidence that it has a strong genetic component. Fibrillin-1 (FBN-1) is the disease gene for Marfan's syndrome and an FBN-1 polymorphism has been associated with large artery stiffening and elevated pulse pressure (PP) in patients with cardiovascular disease. The aim of this study was to investigate the possible influence of the common FBN-1 genotypes on arterial stiffness in a large cohort of healthy individuals.", 'A total of 742 individuals free from cardiovascular disease or risk factors were studied. Aortic pulse wave velocity (PWV) and augmentation index (AIx), blood pressure, lipids and glucose were assessed. Genomic DNA was extracted, and genotyping for the FBN-1 variable nucleotide tandem repeat (VNTR) was performed using a CEQ 8000 sequencer.', 'The mean age (+/- SEM) of the cohort was 49 +/- 1 years. The three common VNTR genotypes accounted for 87.1% of the population frequency. Their frequencies were: 52.3%, 2-2; 16.3%, 2-3; 18.5% 2-4. There were no significant differences in the blood pressure, AIx, PWV, lipids or body mass index among the common genotypes. Moreover, the FBN-1 genotype was not associated with either aortic PWV or other measures of stiffness after correction for other confounding factors.']
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['Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin.', "We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL."]
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['The study aim was to demonstrate that a new database tool for assessment of surgical resident operative skills discerns predictable progression in those skills over successive residency years for specific index case types.', "A Web-based interactive database (OpRate) was used to assess selected aspects of resident operative performance as determined by supervising attending surgeons in a medium-sized residency (5-6 residents per postgraduate year [PGY]). This assessment consisted of (1) 3 questions pertaining to patient information, technical, and disease-specific preparedness; (2) 4 laparoscopic technical skills questions pertaining to tissue handling, dexterity, planning, and ability to function independently; and (3) similar open technical skills questions, with the addition of 2 questions defining knot tying ability. Two years of assessment data were examined for cholecystectomy (CH), appendectomy (AP), colon resection (CR), ventral hernia repair (VH), and inguinal hernia repair (IH). Mean scores for total, technical, and preparedness responses, as well as each response area were compared for successive training years for each case type. Mean performance data between postgraduate years were compared by ANOVA, and interitem reliability was assessed by Cronbach's alpha determinations.", "OpRate data for 579 cases (142 CH, 67 AP, 73 CR, 202 IH, and 95 VH) were examined. Significant incremental increases in open and laparoscopic technical skills scores by training year were observed for all case types (ANOVA, p < 0.0001). Individual technical skills as well as technical and disease-specific preparedness response areas also demonstrated significant improvement by successive training year. Cronbach's alpha determinations were 0.80-0.94 for the preparedness test items and the skills performance scores for all assessed procedures."]
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['Metabolic abnormalities are more associated with central obesity than peripheral obesity, but the underlying mechanisms are largely unknown. The present study was to identify serum metabolic biomarkers which distinguish metabolically unhealthy centrally obese (MUCO) from metabolically healthy peripherally obese (MHPO) individuals.', 'A two-stage case-control study design was employed. In the discovery stage, 20 individuals (10 MHPO and 10 MUCO) were included and in the following validation stage, 79 individuals (20 normal weight (NW), 30 MHPO, 29 MUCO) were utilized. Study groups were matched for age, sex, physical activity and total dietary calorie intake with MHPO and MUCO additionally matched for BMI. Metabolic abnormality was defined as: 1) HOMA-IR\u2009>\u20094.27 (90(th) percentile), 2) high-density lipoprotein cholesterol\u2009<\u20091.03\xa0mmol/L in men and\u2009<\u20091.30\xa0mmol/L in women, 3) fasting blood glucose\u2009≥\u20095.6\xa0mmol/L, and 4) waist circumference\u2009>\u2009102\xa0cm in men and\u2009>\u200988\xa0cm in women. MUCO individuals had all of these abnormalities whereas MHPO and NW individuals had none of them. A targeted metabolomics approach was performed on fasting serum samples, which can simultaneously identify and quantify 186 metabolites.', 'In the discovery stage, serum leucine, isoleucine, tyrosine, valine, phenylalanine, alpha-aminoadipic acid, methioninesulfoxide and propionylcarnitine were found to be significantly higher in MUCO, compared with MHPO group after multiple testing adjustment. Significant changes of five metabolites (leucine, isoleucine, valine, alpha-aminoadipic acid, propionylcarnitine) were confirmed in the validation stage.']
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['CTDP1 catalyzes serine phosphorylation and dephosphorylation of the mobile carboxy-terminal domain of the RNA polymerase II. It is conserved among eukarya and is essential for cell growth for its ability in regulation of transcription machinery. However, its function in the process of tumorigenesis is unclear. In the present study, we aim to explore the roles of CTDP1 in the progression of human lung cancer. To our knowledge, this is the first study that reports the functions of CTDP1 in human lung cancer.', 'We first detected the expression level of CTDP1 in four human lung cancer cell lines: H-125, H1299, LTEP-A-2 and NCI-H446 by semiquantitative RT-PCR. We compared the expression level of CTDP1 in lung cancer tissues and paired adjacent normal tissues on 29 pathologically confirmed patients by real-time quantitative PCR. To further explore the effect of CTDP1 on cell proliferation, a lentiviral vector expressing CTDP1 short hairpin RNA (shRNA) was constructed and infected into human lung cell lines H1299. Interference efficiency was determined by western blot analysis and real-time quantitative PCR. The effects of knockdown of CTDP1 on cell growth, cell cycle and apoptosis and cell colony formation were explored by Cellomics, fluorescence-activated cells sorting and fluorescence microscopy, respectively.', 'CTDP1 was expressed in all four human lung cancer cell lines. The expression of CTDP1 in tumor tissues was significantly higher than paired adjacent normal tissues in 29 patients with lung cancer. The expression of CTDP1 was markedly reduced in cells infected with lentivirus delivering shRNA against CTDP1. Inhibition of CTDP1 expression significantly suppressed cell growth, induced G0/G1 phase arrest and repressed cell colony formation.']
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['We investigated whether tacrolimus (FK506) can inhibit neointimal formation in arterialised vein grafts in rats.', 'Lewis iliolumbar veins were implanted into the abdominal aorta of isogeneic rats. Animals in the treatment groups had daily intramuscular injections of tacrolimus at 0.2 mg/kg (group B) and 0.1 mg/kg (Group C), respectively. The control group A had no treatment. Light microscope evaluations of arterialised vein grafts were performed 30 days after operation. We determined the presence of endothelial cells, the thickness of intima and media, and the degree of infiltration by MHC class II positive, CD4 positive, and CD8 positive cells into the adventitia.', 'The intimal thickness in group B (5.0±1.0 µm) was statistically lower (P < 0.05) when compared to group C (7.0±3.0 µm). The intimal thickness in untreated group A (12.7±7.0 µm) was statistically higher (P < 0.01) when compared to both treated groups B and C, respectively. The medial thickness and degree of adventitial infiltration by MHC class II positive, CD8 positive, and CD4 positive cells did not differ between groups.']
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['Previous studies have demonstrated that neonatal suppression of rapid eye movement (REM) sleep by pharmacologic agents, particularly clomipramine, produces adult depressive behavior. These findings suggest the hypothesis that REM sleep deprivation (RSD) mediates the depressogenic behaviors of neonatally administered antidepressant drugs. Drug suppression of RSD, however, was thought to be confounded by the other effects of the drugs. The current study was aimed to show the adult effect of neonatal RSD in rats by instrumental means, ie, a computer-controlled shaking method.', 'Three treatment groups were studied: an instrumental RSD group, a yoked control group, and a nonshaken, maternally separated, control group. All treatments began at the age of 14 days and lasted for 7 days. Adult behavior measurements including tests of sexual activity, locomotor activity, shock-induced fighting, and sleep recording were subsequently performed.', 'The major findings of our investigation were that rats subjected to neonatal instrumental RSD demonstrated diminished sexual activity, decreased aggressive behavior, increased percentage of REM sleep, and decreased wake-REM sleep ratio compared with yoked control rats. These data are compatible with the findings from adult rats subjected to neonatal treatment with the REM-sleep suppressant, clomipramine, and supports the hypothesis that neonatal RSD results in adult depressive abnormalities.']
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['Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).', 'To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT.', 'Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard.', 'Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P\u2009<\u20090.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%).']
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['In women with anorexia nervosa, elevated fasting peptide YY (PYY) is associated with decreased bone mineral density (BMD). Prior research from our lab has demonstrated that fasting total PYY concentrations are elevated in exercising women with amenorrhea compared to ovulatory exercising women.', 'The purpose of this study was to assess the association between fasting total PYY, average monthly estrogen exposure and BMD in non-obese premenopausal exercising women.', 'Daily urine samples were collected and assessed for metabolites of estrone 1-glucuronide (E1G) and pregnandiol glucuronide (PdG) for at least one menstrual cycle if ovulatory or a 28-day monitoring period if amenorrheic. Fasting serum samples were pooled over the measurement period and analyzed for total PYY and leptin. BMD and body composition were assessed by dual-energy X-ray absorptiometry. Multiple regression analyses were performed to determine whether measures of body composition, estrogen status, exercise minutes, leptin and PYY explained a significant amount of the variance in BMD at multiple sites.', 'Premenopausal exercising women aged 23.8±0.9years with a mean BMI of 21.2±0.4kg/m(2) exercised 346±48min/week and had a peak oxygen uptake of 49.1±1.8mL/kg/min. Thirty-nine percent (17/44) of the women had amenorrhea. Fasting total PYY concentrations were negatively associated with total body BMD (p=0.033) and total hip BMD (p=0.043). Mean E1G concentrations were positively associated with total body BMD (p=0.033) and lumbar spine (L2-L4) BMD (p=0.047). The proportion of variance in lumbar spine (L2-L4) BMD explained by body weight and E1G cycle mean was 16.4% (R(2)=0.204, p=0.012). The proportion of variance in hip BMD explained by PYY cycle mean was 8.6% (R(2)=0.109, p=0.033). The proportion of variance in total body BMD explained by body weight and E1G cycle mean was 21.9% (R(2)=0.257, p=0.003).']
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['Pro-inflammatory cytokines play an important role in osteoarthritis (OA). In osteoarthritic cartilage, chondrocytes exhibit an alteration in mitochondrial activity. This study analyzes the effect of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) on the mitochondrial activity of normal human chondrocytes.', "Mitochondrial function was evaluated by analyzing the activities of respiratory chain enzyme complexes and citrate synthase, as well as by mitochondrial membrane potential (Deltapsim) and adenosine triphosphate (ATP) synthesis. Bcl-2 family mRNA expression and protein synthesis were analyzed by RNase protection assay (RPA) and Western-blot, respectively. Cell viability was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and apoptosis by 4', 6-diamidino-2-phenylindole dihydrochloride (DAPI) stain. Glycosaminoglycans were quantified in supernatant by a dimethyl-methylene blue binding assay.", 'Compared to basal cells, stimulation with TNFalpha (10 ng/ml) and IL-1beta (5 ng/ml) for 48 h significantly decreased the activity of complex I (TNFalpha=35% and IL-1beta=35%) and the production of ATP (TNFalpha=18% and IL-1beta=19%). Both TNFalpha and IL-1beta caused a definitive time-dependent decrease in the red/green fluorescence ratio in chondrocytes, indicating depolarization of the mitochondria. Both cytokines induced mRNA expression and protein synthesis of the Bcl-2 family. Rotenone, an inhibitor of complex I, caused a significant reduction of the red/green ratio, but it did not reduce the viability of the chondrocytes. Rotenone also increased Bcl-2 mRNA expression and protein synthesis. Finally, rotenone as well as TNFalpha and IL-1beta, reduced the content of proteoglycans in the extracellular matrix of normal cartilage.']
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["To examine the Chinese tobacco industry's claim that herbal cigarettes are less harmful than regular cigarettes.", "The study design was a cross-sectional survey. One hundred thirty-five herbal cigarette smokers and 143 regular smokers from one city in China completed a questionnaire on smoking behavior and provided a urine sample. The main outcome measures were cotinine and trans-3'-hydroxycotinine in all samples, and polycyclic aromatic hydrocarbon metabolites (PAH; 1-hydroxypyrene, naphthols, hydroxyfluorenes, and hydroxyphnanthrenes) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and NNAL-glucuronide in randomly selected 98 samples (47 from the herbal smokers' group and 51 from the regular smokers' group). Values were normalized by creatinine to correct for possible variability introduced by dilution or concentration of the urine.", "Health concern was among the main reasons that smokers switched to herbal cigarettes from regular cigarettes. Smokers reported increased consumption after switching to herbal cigarettes from regular cigarettes. For all the four markers analyzed (cotinine, trans-3'-hydroxycotinine, total NNAL, and total PAHs), we observed no significant difference in the levels (P = 0.169, P = 0.146, P = 0.171, and P = 0.554, respectively) between smokers of herbal cigarettes and smokers of regular cigarettes. Both total NNAL and total PAHs were significantly correlated with cotinine and trans-3'-hydroxycotinine (P < 0.001 for all four correlations)."]
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['To investigate the effects of the rate of increase in airway pressure and duration of lung recruitment maneuvers in experimental pulmonary and extrapulmonary acute lung injury.', 'Prospective, randomized, controlled experimental study.', 'University research laboratory.', 'Fifty adult male Wistar rats.', 'Acute lung injury was induced by Escherichia coli lipopolysaccharide either intratracheally (pulmonary acute lung injury) or intraperitoneally (extrapulmonary acute lung injury). After 24 hours, animals were assigned to one of three different recruitment maneuvers, targeted to maximal airway pressure of 30\u2009cm H2O: 1) continuous positive airway pressure for 30 seconds (CPAP-30); 2) stepwise airway pressure increase (5\u2009cm H2O/step, 8.5 s at each step) over 51 seconds (STEP-51) to achieve a pressure-time product similar to that of CPAP-30; and 3) stepwise airway pressure increase (5\u2009cm H2O/step, 5 s at each step) over 30 seconds with maximum pressure sustained for a further 30 seconds (STEP-30/30).', 'All recruitment maneuvers reduced static lung elastance independent of acute lung injury etiology. In pulmonary acute lung injury, CPAP-30 yielded lower surfactant protein-B and higher type III procollagen expressions compared with STEP-30/30. In extrapulmonary acute lung injury, CPAP-30 and STEP-30/30 increased vascular cell adhesion molecule-1 expression, but the type of recruitment maneuver did not influence messenger ribonucleic acid expression of receptor for advanced glycation end products, surfactant protein-B, type III procollagen, and pro-caspase 3.']
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['The purpose of this study was to investigate the association of telomere length in peripheral blood leukocytes with the severity of biliary atresia (BA).', 'One hundred and fourteen BA patients and 114 age-matched healthy controls were enrolled. Relative telomere length (RTL) was assessed using a quantitative real-time polymerase chain reaction. Multivariate regression analysis was used to estimate RTL as an independent risk factor of BA. Receiver operating characteristic curve analysis was used to calculate the accuracy of biomarkers in the prediction of liver cirrhosis.', 'BA patients had significantly shorter telomeres than healthy controls (p < 0.0001). The RTL in BA patients with jaundice was considerably lower than that of patients without jaundice (p = 0.005). Moreover, RTL was markedly shorter in patients with cirrhosis (F4), as compared to patients with mild fibrosis (F2) and non-fibrosis (F0-F1, p < 0.0001). Logistic regression analysis indicated that short RTL was associated with a higher risk of liver cirrhosis in BA. Tertile analysis showed a dose-response effect for this association (p trend < 0.0001). Additionally, RTL in BA children revealed a negative correlation with age (r = -0.50, p < 0.001). We noted an association between reduction of RTL and liver stiffness scores, adjusted for age and gender (b = -0.01, p < 0.0001). Short RTL can be employed to distinguish cirrhosis patients from non-cirrhosis patients (AUC = 0.78). Further analysis showed a linear correlation between leukocyte RTL and liver RTL in BA patients (r = 0.83, p < 0.001).']
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['Metastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC.', 'HMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion.', 'TSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC.']
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['The burden of inflammatory bowel disease [IBD] in health care is high. We conducted research on the temporal changes in the incidence of paediatric IBD [PIBD] using nationwide registry-based data in Finland.', "All PIBD cases diagnosed at less than 20 years of age during 1987-2014 [in total, 5415 patients] were retrieved from a database documenting reimbursements for drug costs. Incidence rates were calculated by dividing the number of annual new PIBD cases by the size of the paediatric population at risk during each calendar year. Temporal trends in the incidences of PIBD and its subtypes, ulcerative colitis [UC] and Crohn's disease [CD], were estimated using Poisson regression analyses.", 'The mean annual incidence of PIBD increased from 7/100000 for the years 1987-1990 to 23/100000 for the years 2011-2014. The average rate of increase was 4.1% (95% confidence interval [CI]: 3.6-4.5) per annum. In the period 2000-2014, the increase rate in the annual incidence of UC [3.8%; 95% CI: 2.7-5.0], was steeper than for CD [2.5%; 95% CI: 1.0-3.8]. The most pronounced increase occurred in UC among adolescents aged 16-19 years [4.8%; 95% CI: 2.9-6.7]. For children less than 10 years of age, the rate of change remained low. Approximately 0.17% of the birth cohort for the years 1999-2000 was diagnosed with PIBD by the age of 14 years.']
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['The aims of the following experiments were to characterize antidiabetic in\xa0vitro and in\xa0vivo activity of the polyphenol-rich aqueous extract of Rutgers Scarlet Lettuce (RSL).', 'RSL extract (RSLE) and isolated compounds were evaluated for inhibitory effects on glucose production as well as tumor necrosis factor alpha-dependent inhibition of insulin activity in H4IIE rat hepatoma cells. Additionally, high-fat diet-induced obese mice were treated with RSLE (100 or 300 mg/kg), metformin (250 mg/kg), or vehicle (water) for 28 d by oral administration and insulin and oral glucose tolerance tests were conducted. Tissues were harvested at the end of the study and evaluated for biochemical and physiological improvements in metabolic syndrome conditions.', 'A polyphenol-rich RSLE, containing chlorogenic acid, cyanidin malonyl-glucoside, and quercetin malonyl-glucoside, was produced by simple boiling water extraction at pH 2.0. In\xa0vitro, RSLE and chlorogenic acid demonstrated dose-dependent inhibition of glucose production. In\xa0vivo, RSLE treatment improved glucose metabolism measured by oral glucose tolerance tests, but not insulin tolerance tests. RSLE treated groups had a lower ratio of liver weight to body weight as well as decreased total liver lipids compared with the control group after 28 d of treatment. No significant differences in plasma glucose, insulin, cholesterol, and triglycerides were observed with RSLE-treated groups compared with vehicle control.']
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['We investigated the actions of isoflurane and propofol on neuronal windup in the spinal cord of intact rats. We hypothesized that propofol would depress windup more than isoflurane.', 'In a cross-over design, rats received 0.8 and 1.2 minimum alveolar concentration (MAC) isoflurane and 0.8 and 1.2 ED50 (effective dose(50%)) of propofol, as recordings were made from single units in the lumbar cord (n = 13). Electrical stimuli were applied (20 stimuli at 0.1, 1, and 3 Hz). Neuronal responses were analyzed for those occurring in the C-fiber range (100-400 ms after each stimulus), combined C-fiber and afterdischarge range (100-1000 ms) and the 100-333 ms range for the 3 Hz stimuli. Absolute windup was also calculated (the sum of action potentials for 20 stimuli - 20 x response to the first stimulus).', 'At 1 Hz, total action potentials (mean, standard error) summed across the 20 stimuli (100-1000 ms range) were 571 +/- 106 and 742 +/- 214 for isoflurane (at 0.8 and 1.2 MAC) and 586 +/- 148 and 641 +/- 143 for propofol (at 0.8 and 1.2 ED50), respectively (P = NS); corresponding values for the 0.1 Hz stimuli were 345 +/- 104, 370 +/- 108, 430 +/- 86, and 403 +/- 106 (P = NS), and for the 3 Hz stimuli (100-333 ms range) were 266 +/- 66, 333 +/- 76, 343 +/- 85, and 252 +/- 72 (P = NS). Absolute windup in the 100-1000 ms range was greater for 1.2 MAC isoflurane at 1 Hz (445 +/- 82, P < 0.01), when compared with absolute windup at 0.8 MAC isoflurane and 0.8 and 1.2 ED50 propofol (232 +/- 31, 88 +/- 65, and 210 +/- 41, respectively).']
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['Coexistent respiratory failure and metabolic alkalosis is a common finding. Acidotic diuretics cause a fall in pH that may stimulate respiration.', 'The purpose of the study was to evaluate the effectiveness of short-term treatment with acetazolamide for combined respiratory failure and metabolic alkalosis.', 'A randomised, placebo-controlled and double-blind parallel group trial where oral acetazolamide 250 mg three times a day for 5 days were administered to patients hospitalised for respiratory failure because of a pulmonary disease (Pa O2 ≤ 8 kPa and/or Pa CO2 ≥ 7 kPa) who had concurrent metabolic alkalosis [base excess (BE) ≥ 8 mmol/L]. Pa O2 after 5 days was the primary effect variable. Secondary effect variables were Pa CO2 , BE and pH on day 5, and the total number of days in hospital.', 'Of 70 patients enrolled (35 in each group), data from 54 were analysed per protocol, while last observation carried forward was used for the remaining 16. During the 5-day treatment, Pa O2 increased on average 0.81 kPa in the placebo group and 1.41 kPa in the acetazolamide group. After adjustment for baseline skewness, the difference was statistically significant (adjusted mean difference 0.55 kPa, 95% confidence interval 0.03-1.06). Pa CO2 decreased in both groups, but the difference was not statistically significant. As expected, pH and BE decreased markedly in the acetazolamide group.']
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['Previously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.', 'Neonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.', 'Re-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).']
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['To compare the effect of staffing with general surgeons vs trauma specialists on patient outcome at a trauma center.', 'The care of injured patients at a level I urban trauma center serving a population of 2.5 million was the responsibility of 12 surgeons (10 general surgeons and 2 trauma specialists) between January 1 and June 30, 1996 (group 1). Between July 1 and December 31, 1996 (group 2), trauma was the responsibility solely of 4 trauma specialists. An additional comparison was made with those patients in group 1 who were admitted to the general surgeons (group 1A). The outcomes and quality of care for these periods, as determined by the quality assurance screens, were retrospectively analyzed and compared.', 'Urban, tertiary care, level I trauma center.', "Each trauma and burn patient admitted during the study periods is included in this study. Upon the patient's discharge from the hospital, specially trained nurses completed a review of the patient's stay and entered it into the TraumaOne database (Lancet Technology Inc, Cambridge, Mass). There were 693 trauma patients in group 1 (472 in group 1A) and 734 patients in group 2.", 'Mortality, length of stay, and 16 quality assurance screens were quantified and compared using chi(2) analyses and t tests.', 'The age and sex of the 2 groups were similar. The mortality rate was 6.2% (43/693) in group 1, 6.1% (29/472) in group 1A, and 6.5% (48/734) in group 2 (P = .80 and P = .78, respectively). When stratified by injury severity score (ISS), lengths of stay were statistically similar, except for patients with an ISS of 0 to 7. Patients with an ISS of 0 to 7 in groups 1 and 1A stayed a mean of 2.6 days, compared with 3.2 days for group 2 (P = .01 and P = .02, respectively). The results of quality assurance screens (missed injury, wound infection, readmission, and 13 others) were similar in the 2 groups.']
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['The aim of the study is to assess radiology resident training experience in cardiac magnetic resonance imaging (MRI), positron emission tomography (PET), obstetrical (OB) ultrasound (US), carotid US, and barium esophagram.', 'One hundred eighteen radiology residents completed surveys. Surveys assessed resident year of residency training, hospital size, program affiliation with an academic institution, state, performance of the examinations listed, number of examinations performed per week, and number of weeks spent on rotations for each modality. The study was approved by the institutional review board and was Health Insurance Portability and Accountability Act (HIPAA) compliant. t-Test and chi-square test were performed, and results were analyzed for statistical significance.', 'Most (94 respondents; 80%) respondents were third-year residents, 101 residents (86%) stated their program was affiliated with an academic institution, 92 residents (78%) performed cardiac MRI, 104 (88%) performed PET, 84 (71%) performed OB US, 71 (60%) performed carotid US (one did not respond), and all performed esophagrams (although one did not respond). Only performance of cardiac MRI and PET correlated positively with a larger average hospital size (P < .01). Residents at an academically affiliated program were significantly more likely to perform cardiac MRI (P < .05). Geographic region significantly affected likelihood of performance of cardiac MRI only.']
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['Maximum intensity projection (MIP) images might be useful in helping to differentiate small pulmonary nodules from adjacent vessels on thoracic multidetector CT (MDCT).', 'The aim was to evaluate the benefits of axial MIP images over axial source images for the paediatric chest in an interobserver variability study.', 'We included 46 children with extra-pulmonary solid organ malignancy who had undergone thoracic MDCT. Three radiologists independently read 2-mm axial and 10-mm MIP image datasets, recording the number of nodules, size and location, overall time taken and confidence.', 'There were 83 nodules (249 total reads among three readers) in 46 children (mean age 10.4\u2009±\u20094.98 years, range 0.3-15.9 years; 24 boys). Consensus read was used as the reference standard. Overall, three readers recorded significantly more nodules on MIP images (228 vs. 174; P < 0.05), improving sensitivity from 67% to 77.5% (P < 0.05) but with lower positive predictive value (96% vs. 85%, P < 0.005). MIP images took significantly less time to read (71.6\u2009±\u200943.7 s vs. 92.9\u2009±\u200948.7 s; P < 0.005) but did not improve confidence levels.']
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['Recent evidence suggests that the prostate cancer (PCa)-specific up-regulation of certain genes such as AMACR, EZH2, PSGR, PSMA and TRPM8 could be associated with an aberrant expression of non-coding microRNAs (miRNA).', 'In silico analyses were used to search for miRNAs being putative regulators of PCa-associated genes. The expression of nine selected miRNAs (hsa-miR-101, -138, -186, -224, -26a, -26b, -374a, -410, -660) as well as of the aforementioned PCa-associated genes was analyzed by quantitative PCR using 50 malignant (Tu) and matched non-malignant (Tf) tissue samples from prostatectomy specimens as well as 30 samples from patients with benign prostatic hyperplasia (BPH). Then, correlations between paired miRNA and target gene expression levels were analyzed. Furthermore, the effect of exogenously administered miR-26a on selected target genes was determined by quantitative PCR and Western Blot in various PCa cell lines. A luciferase reporter assay was used for target validation.', 'The expression of all selected miRNAs was decreased in PCa tissue samples compared to either control group (Tu vs Tf: -1.35 to -5.61-fold; Tu vs BPH: -1.17 to -5.49-fold). The down-regulation of most miRNAs inversely correlated with an up-regulation of their putative target genes with Spearman correlation coefficients ranging from -0.107 to -0.551. MiR-186 showed a significantly diminished expression in patients with non-organ confined PCa and initial metastases. Furthermore, over-expression of miR-26a reduced the mRNA and protein expression of its potential target gene AMACR in vitro. Using the luciferase reporter assay AMACR was validated as new target for miR-26a.']
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['Growth differentiation factor-15 (GDF-15) is an inflammatory molecule that reacts to cell stress. Since major depression is associated with inflammation, we examined whether GDF-15 levels are elevated in patients with late-life depression.', 'Plasma GDF-15 levels were analyzed in 350 patients diagnosed with major depressive disorder in the last six months and 128 non-depressed controls from the Netherlands Study of Depression in Older persons (age ≥ 60 years). Major depressive disorder and age of onset were assessed with the Composite International Diagnostic Interview. Severity of depressive symptoms was measured with the Inventory of Depressive Symptoms (IDS-30). Multiple linear regression models were applied to study depression (diagnosis, onset age, severity, antidepressant drug use) as determinant of GDF-15 level, adjusted for demographic and clinical variables.', 'Plasma GDF-15 levels were 22% higher in patients with major depression compared to controls. Within the depressed group, levels were higher in patients with older age of onset. GDF-15 levels showed a small, positive correlation to the levels of the inflammatory mediators IL-6 and C-reactive protein (r=0.23, and 0.24, p<0.05). This increase was independent from comorbidities, such as cardiovascular disease, rheumatism and diabetes, and anti-inflammatory drugs. However, this increase was dependent on lifestyle factors as smoking, physical activity and alcohol use. Within the depressed subgroup, neither depression severity or antidepressant drug use was associated with GDF-15 levels in the fully adjusted models.']
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['To investigate if child development has a role in unintentional poisoning, by describing the pattern of hospitalization due to unintentional poisoning in children aged 0-4 years in New South Wales by single year of age and then assessing the stability of the age-specific pattern found when analyzed by sex, remoteness of residence, and socioeconomic status.', 'Retrospective descriptive study.', 'New South Wales hospitals from 1994 to 2005.', 'Children aged 0-4 years in the New South Wales Department of Health Inpatient Statistics Collection.', 'Hospitalization due to unintentional poisoning.', 'Hospitalization rates by single year of age and single year of age by three covariates: sex, remoteness of residence, and socioeconomic status.', 'Children aged 1-3 years had the highest rates of hospitalization due to unintentional poisoning, and this pattern persisted over time. The same age-specific pattern was seen for both boys and girls, but rates were significantly higher for boys than girls at age 3 years (RR = 1.46, 95% CI 1.31 to 1.62). The age-specific pattern persisted when the covariates remoteness of residence and socioeconomic status were controlled for.']
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['Plant-derived phytochemicals consisting of phenols and flavonoids possess antioxidant properties, eventually rendering a lucrative tool to scavenge reactive oxygen species. This study was carried out to evaluate in vitro antioxidant and cytotoxic potential of methanolic extract and petroleum ether extracts of Smilax zeylanica L. stems.', 'Phytochemical screening was done following standard procedures. Antioxidant activity was tested using several in vitro assays, viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, NO assay, H2O2 assay, CUPRAC assay, FRAP assay and total antioxidant capacity assay. Total phenol and flavonoid contents were determined by colorimetric method. Brine shrimp lethality and MTT cell viability assays were used for cytotoxic potential.', 'Preliminary phytochemical study revealed the presence of flavonoids and glycosides in both extracts. Methanolic extract was found to possess stronger antioxidant potential than petroleum ether extracts in all assays. The IC50 value of methanolic extract was 29.14±0.39 μg/mL, 120.30±3.32 μg/mL and 78.41±5.53 μg/mL in DPPH assay, NO assay and H2O2 assay, respectively. Likewise, total phenol [56.78 mg/g gallic acid (GAE)] and flovonoid [125.69 mg/g quercetin equivalents (QE)] were higher in methanolic extract. In cytotoxicity assays, petroleum ether extract showed stronger activity in both brine shrimp lethality (LC50 2.85±0.13 μg/mL) and MTT cell viability assay (IC50 15.49±1.18 μg/mL).']
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['Administration of preoperative radiotherapy for extremity soft tissue sarcoma improves local control, while allowing for a more conservative surgical resection. During radiation treatment tumor size typically decreases or remains constant. In a subset of patients, however, a size increase in the tumor occurs. Our goal was to investigate the prognosis of patients who had a size increase of at least 20% over the course of preoperative radiotherapy versus those who did not.', 'This retrospective study evaluated 70 patients treated for localized primary STS of the extremities between January 2000 and December 2008. Kaplan-Meier curves for disease-specific and metastasis-free survival were calculated for both groups.', "Sixty-one patients had stable or decrease local tumor size following preoperative radiotherapy and nine patients had an increase of at least 20% in tumor size. There were no statistically significant differences found in disease-specific survival and metastasis-free survival (Gray's test, P = 0.93 and P = 0.68, respectively) among the two groups."]
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['Androgen effects on hepatocellular carcinoma (HCC) remain controversial and androgen ablation therapy to treat HCC also leads to inconsistent results. Here we examine androgen receptor (AR) roles in hepatocarcinogenesis using mice lacking AR in hepatocytes.', 'By using the Cre-Lox conditional knockout mice model injected with carcinogen, we examined the AR roles in hepatocarcinogenesis. We also tested the possible roles of AR in cellular oxidative stress and DNA damage sensing/repairing systems. By using AR degrading compound, ASC-J9, or AR-small interference RNA, we also examined the therapeutic potentials of targeting AR in HCC.', 'We found AR expression was increased in human HCC compared with normal livers. We also found mice lacking hepatic AR developed later and less HCC than their wild-type littermates with comparable serum testosterone in both male and female mice. Addition of functional AR in human HCC cells also resulted in the promotion of cell growth in the absence or presence of 5alpha-dihydrotestosterone. Mechanistic dissection suggests that AR may promote hepatocarcinogenesis via increased cellular oxidative stress and DNA damage, as well as suppression of p53-mediated DNA damage sensing/repairing system and cell apoptosis. Targeting AR directly via either AR-small interference RNA or ASC-J9 resulted in suppression of HCC in both ex vivo cell lines and in vivo mice models.']
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['To investigate the signal pathway of honokiol-induced apoptosis on human colorectal carcinoma RKO cells and to evaluate whether p53 and p53-related genes were involved in honokiol-treated RKO cells.', 'Cell cycle distribution and subdiploid peak were analyzed with a flow cytometer and DNA fragment with electrophoresis on agarose gels. Transcriptional level of Bax, Bcl-2, Bid and Bcl-xl was accessed by RT-PCR. Western blotting was used to measure p53 protein expression and other factors related to apoptosis. Proliferation inhibition of two cell lines (RKO, SW480) with high expression of p53 and one cell line with p53 negative expression (LS180) was monitored by MTT assay.', 'Honokiol induced RKO cell apoptosis in a dose-dependent manner. The mRNA expression level and protein level of Bid were up-regulated while that of Bcl-xl was down-regulated, but no changes in Bax and Bcl-2 were observed. Western blotting showed p53 expression had no remarkable changes in honokiol-induced RKO cell apoptosis. LS180 cells treated with honokiol exhibited apparent growth inhibition like RKO cells and Sw480 cells.']
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['Physiotherapy is integral to modern trauma care. Early physiotherapy and mobility have been shown to improve outcomes in patients with isolated injuries; however, the optimal intensity of physiotherapy in the multitrauma patient population has not yet been examined. The primary aim of this study was to determine whether an intensive physiotherapy program resulted in improved inpatient mobility.', 'We conducted a single-center prospective randomized controlled study of 90 consecutive patients admitted to the Alfred Hospital (a Level 1 trauma center) in Australia between October 2011 and June 2012 who could participate in ward-based physiotherapy. Participants were allocated to either usual care (daily physiotherapy treatment, approximately 30 minutes) or intensive physiotherapy (usual care plus two additional 30-minute treatments each day). The primary outcome measure was the modified Iowa Level of Assistance (mILOA) score, collected by a blinded assessor at Days 3 and 5 (or earlier if discharged). Secondary measures included physical readiness for discharge, hospital and rehabilitation length of stay, a patient confidence and satisfaction scale, and quality of life at 6 months.', 'Groups were comparable at baseline. Participants in the intensive physiotherapy group achieved significantly improved mILOA scores on Day 3 (median, 7 points compared with 10 points; p = 0.02) and Day 5 (median, 7.5 points compared with 16 points; p = 0.04) and were more satisfied with their care (p = 0.01). There was no difference between groups in time to physical readiness, discharge destination, length of stay, or quality-of-life measures.']
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['Steatosis is a defining feature of nonalcoholic fatty liver disease (NAFLD). However, evidence that severity of steatosis can predict adverse outcomes in NAFLD or nonalcoholic steatohepatitis (NASH) is lacking. The aim of this study was to determine whether steatosis assessed by computed tomography (CT) imaging predicts adverse outcomes in diabetic patients at risk for NAFLD/NASH.', 'We studied deaths, liver-related and cardiovascular adverse outcomes in a 5-year retrospective observational cohort of 2343 type 2 diabetic patients in a large care network who had noncontrast CT imaging for clinical indications. We measured steatosis by subtraction of spleen from liver attenuation, a method that showed low sensitivity (0.417) and high specificity (0.882) compared with histopathological scoring. We evaluated outcomes prediction using multivariate Cox proportional hazards modelling of steatosis both as a categorical (≥ 30%) and continuous variable.', 'Steatosis ≥ 30% was present in 233 (9.9%) of the cohort at baseline. Over 5 years, there were 372 total deaths, 18 liver-related and 99 cardiovascular deaths, 48 liver transplants, 51 occurrences of hepatic encephalopathy, 41 hepatocellular carcinomas, 653 myocardial infarctions, 66 strokes, 180 occurrences of angina, 735 occurrences of arrhythmia and 772 occurrences of congestive heart failure. Steatosis had no predictive value for any adverse outcome. Patients with steatosis averaged 8 years younger than those without it. Age had a strong covariate influence on occurrence of total deaths, cardiovascular deaths, myocardial infarctions, arrhythmias and congestive heart failure.']
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['To compare the microRNA (miRNA) profiles of uterine endometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS), and to compare the miRNA signatures of primary and metastatic uterine LMS.', 'Eight primary LMS, 9 primary ESS and 8 metastatic LMS were analyzed for miRNA profiles using TaqMan Human miRNA Array Cards. Findings for 20 differentially expressed miRNAs were validated in a series of 44 uterine sarcomas (9 primary uterine ESS, 17 primary uterine LMS, 18 metastatic LMS) using qPCR. Frizzled-6 protein expression was analyzed in 30 LMS (15 primary, 15 metastases). Frizzled-6 was silenced in SK-LMS-1 uterine LMS cells using siRNA and the effect on invasion, wound healing and matrix metalloproteinase-2 (MMP2) activity was assessed.', 'Ninety-four miRNAs were significantly differentially expressed in ESS and LMS, of which 76 were overexpressed in ESS and 18 overexpressed in LMS. Forty-nine miRNAs were differentially expressed in primary and metastatic LMS, of which 45 were overexpressed in primary LMS and 4 in metastases. Differential expression was confirmed for 10/20 miRNA analyzed using qPCR. Frizzled-6 silencing in SK-LMS-1 cells significantly inhibited cellular invasion, wound healing and MMP-2 activity.']
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['Although mitochondrion-derived markers such as ornithine carbamyltransferase (OCT) and glutamate dehydrogenase (GLDH) have been reported to be good markers for alcohol-induced hepatic injury, their use has been limited due to the notion that mitochondrial markers are less sensitive than cytosol-derived markers. We determined the clinical importance of mitochondrion-derived markers in the evaluation of alcohol-induced hepatotoxicity.', 'Rats were administered alcohol chronically (5-30% ethanol in drinking water with or without high fat diet feeding for 15 weeks) and hepatic damages were evaluated by serum OCT and GLDH, together with other liver enzymes such as alanine aminotransferase and aspartate aminotransferase. Hepatic content of the enzymes was also evaluated in the chronic ethanol feeding model to confirm whether induction of the enzyme in the liver reflects the serum activity.', 'The serum activities of OCT and GLDH increased significantly by chronic ethanol feeding while other markers did not. Although the hepatic content of OCT and GLDH also increased, the serum activities did not correlate with the hepatic activities and the extent of increase in the liver was much less than in serum.']
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['The objective was to identify prognostic factors of disease-free and overall survival in stage I endometrial carcinoma, thereby potentially facilitating the selection of patients who are on high risk for recurrence and who may benefit from transection of a vaginal cuff.', 'In a retrospective review between 1994 and 2004, 340 patients with stage I endometrial carcinoma were managed surgically at two different hospitals in Rostock. The median follow-up was 79 (range 12-161) months. Clinical and histological parameters were compared using the SPSS software package.', 'In the univariate analysis the factors associated with poor disease-free survival in stage I carcinoma were higher tumor grade (P=0.013), and no removed vaginal cuff (P=0.025). The corresponding factor for impaired overall survival was no removed vaginal cuff (P=0.003). All parameters with a P-value<0.25 in the univariate setting were entered into a multivariate analysis. The factors that maintained associated with poor disease-free and overall survival were higher tumor grade and lack of vaginal cuff.']
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['Resident psychiatrists in the Netherlands, unlike their counterparts in other countries, are obliged to undergo 50 hours of personal psychotherapy. In 1994 Trijsburg et al. published the results of a questionnaire that had been completed by psychiatrists, psychologists and other persons training to become psychotherapists.', 'To fnd out how resident psychiatrists in Amsterdam in 2003 characterised and rated the therapy module in their course.', 'Resident psychiatrists in Amsterdam were asked to complete a shortened version of the 1994 questionnaire. The Utrecht Burn-out Scale was added.', 'Personal therapy was greatly appreciated, but the psychotherapists were more convinced of the positive effects than were the residents. Hardly anyone referred to any negative aspects. The residents did not consider personal therapy to be an essential element in their course. Two-thirds of the residents in Amsterdam were female, a large increase compared to the male-female ratio in 1994. The workload of the residents was in accordance with that of other workers in the health care sector.']
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['Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging.', 'Young (4\xa0months) and old (18\xa0months) male C57Bl/6 mice were fed either an ethanol-containing Lieber-DeCarli liquid diet or an isocaloric control diet for 5\xa0weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA.', 'Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5\xa0kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p\xa0=\xa00.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1\xa0kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p\xa0=\xa00.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment.']
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['Surrogate indicators have often been used to estimate intravascular volume to guide fluid management. Brain-type natriuretic peptide (BNP) has been used as a noninvasive adjunct in the diagnosis of fluid overload and as a marker of response to therapy, especially in individuals with congestive heart failure. Similarly, right ventricular end-diastolic volume index (RVEDVI) measurements represent another parameter used to guide fluid resuscitation. The aim of this study was to evaluate whether BNP and RVEDVI are clinically valuable parameters that can distinguish among hypovolemia, euvolemia, and hypervolemia, as measured by blood volume (BV) analysis in critically ill surgical subjects.', "This observational study was part of a prospective, randomized controlled trial. Subjects with pulmonary artery catheters for the treatment of traumatic injuries, severe sepsis/septic shock, cardiovascular collapse, adult respiratory distress syndrome, and postsurgical care were studied. Circulating BV was measured by a radioisotope dilution technique using the BVA-100 Analyzer (Daxor Corporation, New York, NY) within the first 24 hours of acute resuscitation. BV results were reported as percent deviation from the patient's ideal BV based on height and percent deviation from optimum weight. Hypovolemia was defined as less than 0%, euvolemia was defined as 0% to +16%, and hypervolemia was defined as greater than +16% deviation from ideal BV. RVEDVI was measured by continuous cardiac output pulmonary artery catheters (Edwards Lifesciences, Irvine, CA). BNP and RVEDVI measurements obtained with BV analysis were evaluated with Fisher's exact test and regression analysis.", 'In 81 subjects, there was no difference in BV status between those with BNP of 500 pg/mL or greater and BNP of less than 500 pg/mL (p = 0.82) or in those with RVEDVI of 140 mL/m or greater and RVEDVI of less than 140 mL/m (p = 0.43). No linear relationship existed between BV and these parameters.']
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['To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo.', 'A synthetic peptide derived from aa 603-622 of SIVmac251 gp41 was synthesized and tested for immunogenicity in rabbits and SIV-infected rhesus macaques. Next, SIV-naive animals were immunized with either a recombinant vaccinia virus expressing the SIV gp160 envelope glycoprotein (VVrgp160) and boosted three times with aa 603-622 (group 1, four animals), wild-type vaccinia virus and boosted with aa 603-622 (group 2, two animals), or VVrgp160 followed by three doses of an irrelevant peptide (group 3, two animals). Animals were challenged with SIVmac251.', 'Peptide aa 603-622 was immunogenic in rabbits. SIV-infected rhesus monkeys immunized with the peptide developed two-three log increases in antibodies to this peptide and antibodies that could enhance SIV infection in vitro. SIV-naive rhesus macaques in group 1 had higher levels of antibody to the peptide by enzyme-linked immunosorbent assay and higher levels of enhancing antibodies at the time of SIV challenge than the animals in groups 2 or 3. Following challenge with SIVmac251 the group 1 animals had detectable p27 antigen longer than animals in group 2 and 3 and died of simian AIDS before the respective animals in the two control groups (P < 0.05 by log-rank test).']
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['Angiotensin II (Ang II) is a vasoconstrictor but also a growth factor. However, the Ang II type 1 receptor does not have a tyrosine kinase domain that mediates the cellular signals for mitosis. We have shown that Ang II acts via "trans"-activation of the epidermal growth factor receptor (EGFR) to induce activation of tyrosine kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) in vascular smooth muscle cells (VSMCs). To examine whether EGFR is involved in the development of left ventricular hypertrophy (LVH), we inhibited EGFR with a specific antisense oligodeoxynucleotide to attenuate the Ang II-induced cardiovascular hypertrophic effects.', 'The antisense oligodeoxynucleotide to EGFR (EGFR-AS) was designed and tested on Ang II-induced ERK activation in cultured VSMCs. We also investigated the effects of EGFR-AS on LVH and blood pressure (BP) in Ang II-infused hypertensive rats. In VSMCs, EGFR-AS (2.5 micromol/L) reduced EGFR expression and inhibited the Ang II-induced phosphorylation of ERK. In rats, Ang II (150 ng/h for 14 days) increased BP compared with controls (184+/-6 mm Hg versus 122+/-3 mm Hg; n=7; P<0.01). Continuous intravenous infusion of EGFR-AS (2 mg/kg) decreased BP (169+/-8 mm Hg; n=8; P<0.05). Ang II infusion increased the left ventricular/body weight (LV/BW) ratio compared with control rats (2.75+/-0.08 versus 2.33+/-0.07; P<0.01). EGFR-AS, but not EGFR-sense, normalized the LV/BW in Ang II-infused rats (2.32+/-0.06; P<0.01) and attenuated Ang II-enhanced EGFR expression and ERK phosphorylation.']
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['Therapeutic hypothermia (TH) is an acknowledged strategy for neuroprotection for patients suffering from hypoxic-anoxic brain injury (HAI). Albeit similar pathomechanisms of HAI for both brain and heart, moderate TH (32-34°C) has not been established as a heart-protective measure. Therefore, we investigated the cardioprotective effects of moderate TH on oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced injury in HL-1 cardiomyocytes.', 'Cardiac OGD/R injury was induced by exposing HL-1 cardiomyocytes to 0.2% oxygen in serum/glucose-free medium for 6h. OGD injured cells were subsequently re-oxygenated with 21% oxygen in complete medium. Two hypothermic protocols were investigated: Post-OGD cooling to 33.5°C for 24 h initiated at the start of re-oxygenation and intra-OGD cooling to 33.5°C for 24 h initiated after 3 h of OGD and maintained throughout the re-oxygenation phase. Cell viability was determined by LDH and cTnT releases. Mitochondria dysfunction was evaluated by intracellular ATP content and cellular metabolic activity was accessed by MTT reduction. Activation of caspase 3 was analyzed by Western blot.', 'OGD/R-induced injury resulted in increased cell death (higher LDH and cTnT releases), mitochondrial impairment (decreased ATP content), and decreased cellular metabolic activity (decreased MTT reduction). Only intra-OGD cooling attenuated both OGD and OGD-R-induced injuries (significantly decreased LDH and cTnT releases and increased ATP contents and MTT reduction). Furthermore, caspase 3 activation was abated by intra-OGD cooling. No protective effects were observed by post-OGD cooling.']
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['Ultraviolet B (UVB) radiation from sunlight is a known risk factor for human corneal injury. The aim of the present study was to investigate the protective effects of green tea polyphenol epigallocatechin gallate (EGCG) on UVB radiation-induced corneal oxidative damage in male imprinting control region (ICR) mice.', 'Corneal oxidative damage was induced by exposure to UVB radiation at 560 μW/cm(2). The animals received 0%, 0.1%, and 0.01% EGCG eye drops at a 5 mg/ml dose, twice daily for 8 days. Corneal surface damage was graded according to smoothness and the extent of lissamine green staining. Corneal glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), and protein carbonyl levels, as well as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rd) activity in the cornea, were measured to monitor corneal injury.', 'UVB radiation caused significant damage to the corneas, including apparent corneal ulceration and severe epithelial exfoliation, leading to a decrease in SOD, catalase, GSH-Px, GSH-Rd, and GSH activity in the cornea. However, the corneal TBARS and protein carbonyls increased compared with the control group. Treatment with EGCG eye drops significantly (p<0.05) ameliorated corneal damage, increased SOD, catalase, GSH-Px, GSH-Rd, and GSH activity, and decreased the TBARS and protein carbonyls in the corneas compared with the UVB-treated group.']
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['To determine if drip infusion should be discontinued after full recovery of the patient from anaesthesia after minilaparotomy cholecystectomy in uncomplicated cases.', 'A randomised controlled clinical trial on 60 patients, from the waiting list, of cholelithiasis/cholecystitis operated by minilaparotomy cholecystectomy between November 1995 to March 1996. 30 patients did not receive postoperative i.v. drip infusion and in 30 patients 12-24 hours of standard drip transfusion was continued according to the current practice.', 'Single Surgical Unit, SS Hospital, Banaras Hindu University, Varanasi, India.', 'Recognition of clinical indication for continuation of i.v. drip infusion after full recovery from anaesthesia.', 'In the cohorts of 30 patients each who were or were not given i.v. drip infusion after full recovery from anaesthesia following minilaparotomy cholecystectomy the observations on pulse rate, blood pressure, time to first voiding of urine and time to start first oral intake of fluids were identical. However postoperative urinary retention occurred in 6 (20%) patients in whom the IV drip infusion was given.']
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['Inhalation of nitric oxide (NO) selectively dilates the pulmonary circulation and improves arterial oxygenation in patients with adult respiratory distress syndrome (ARDS). In approximately 60% of patients with septic ARDS, minimal or no response to inhaled NO is observed. Because sepsis is associated with increased NO production by inducible NO synthase (NOS2), the authors investigated whether NOS inhibition alters NO responsiveness in rats exposed to gram-negative lipopolysaccharide (LPS).', 'Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli O111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured.', 'Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75+/-0.25, 1.25+/-0.25, 1.75+/-0.25 mmHg) than in lungs of control rats (3+/-0.5, 4.25+/-0.25, 4.5+/-0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75+/-0.25, 4.5+/-0.25, 4.5+/-0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0+/-1.0, 4.0+/-1.0, 4.0+/-0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75+/-0.25, 2.25+/-0.5, 2.75+/-0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness.']
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['C-reactive protein (CRP) and high-density lipoprotein (HDL) cholesterol are well-known cardiovascular predictors. However, the joint effect of these parameters on long-term mortality has not been established.', 'We studied a total of 92,500 subjects older than 20 years who underwent routine health examination at the three health care centers affiliated with Seoul National University. High-sensitivity CRP and the lipid profile were obtained at baseline. Subjects were followed for a median of 45.5 months. Mortality data were obtained from the National Statistics Office of Korea.', 'There were 649 deaths (0.7%) during the follow-up. The leading cause of death was cancer. The subjects who died were significantly older, had a male predominance, and had increased levels of inflammatory markers. A significant mortality difference was identified according to the CRP and HDL cholesterol levels. Considering both parameters jointly, subjects with a CRP ≥1.4 mg/L (highest quartile) and HDL cholesterol <45 mg/dL (lowest quartile) were at the highest risk for all-cause mortality, even after adjusting for covariates (hazard ratio 2.29, 95% confidence interval, 1.83~2.87). After matching on the propensity score, 6304 subjects with a high CRP and low HDL cholesterol were at high risk of death (hazard ratio 2.52, 95% confidence interval, 1.59~4.01). Interestingly, the joint effect of CRP and HDL cholesterol was observed for cardiovascular as well as cancer-related mortality prediction.']
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['To compare the contrast-to-noise ratio (CNR) of advanced liver fibrosis on nonenhanced (NE), gadolinium enhanced (Gd), superparamagnetic iron oxides enhanced (SPIO), and combined contrast-enhanced (CCE) spoiled gradient echoes (SGEs).', 'This retrospective study assessed 83 consecutive patients with cirrhosis and 10 consecutive patients without fibrosis. All patients had NE, Gd, SPIO, and CCE images at 1.5 T. A total of six breathhold SGE sequences with varying imaging parameters were assessed. MR images were evaluated qualitatively and, in 15 cirrhotics who underwent liver transplantation, compared to gross pathology. CNR of fibrosis to background liver was compared across sequences and contrast enhancement types.', 'In cirrhotic patients, CCE images on all sequences showed fibrosis as a meshwork of high-signal 1-mm to 3-mm thick reticulations surrounding 2-mm to 5-mm low-signal regenerative nodules. Fibrosis was less visible on Gd and SPIO images and was barely visible on NE images. CNR was significantly higher for CCE than for NE, Gd, or SPIO images in eight of nine comparisons (P < 0.0001-0.05). The liver had a homogeneous appearance in subjects without fibrosis.']
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['To determine the prevalence of antibodies directed against the equatorial segment of the spermatozoon in (a) serum in both sexes in relation to age and fertility status and (b) semen of infertile men with tail-to-tail sperm agglutination in relation to in vitro sperm penetration capacity.', 'Serum samples were obtained from 30 neonates, 11 prepubertal children, 30 adolescents, 60 adults aged 20-50 years, and 60 adults over the age of 70. Semen samples were obtained from 62 men with normal sperm counts and sperm morphology but with tail-to-tail agglutination.', 'Sperm antibodies were demonstrated with an immunoperoxidase assay. Sperm penetration capacity was measured with a modified Kremer capillary test.', 'Serum anti-sperm antibodies were absent in children but appeared in teen-age boy (10%) and in adult men (20%) and women (30%). Lower prevalence of serum anti-sperm antibodies was noted for old individuals of both sexes (6-10%). Among individuals with a history of infertility, a significantly higher frequency of anti-sperm antibody-positive men (P < .001) and (P < .05) was found as compared to fertile controls. Presence of IgA antibodies bound to the equatorial segment of spermatozoa was associated with impaired in vitro sperm penetration capacity. No IgG or IgM anti-sperm antibodies bound to the equatorial segment were demonstrable.']
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['Depletion of neutrophils (PMNs) and inhibition of PMN endothelial adhesion ameliorate post-ischemic lung reperfusion injury. Lidocaine reduces PMN adhesion to endothelial surfaces in vivo, and inhibits upregulation of PMN-CD11b/CD18 (Mac-1) in vitro. We evaluated the effect of lidocaine on reperfusion injury, PMN adhesion, and PMN migration in preserved lung allografts.', 'Donor lungs were flushed with modified Euro-Collins solution (4 degrees C) after prostaglandin E1 administration (250 micrograms), inflated with 550 mL (inspired oxygen fraction = 1.0), and stored for 24 hours at 1 degree C. Left lung allotransplantation was performed in 13 mongrel dogs. Immediately after reperfusion the recipient right pulmonary artery and bronchus were ligated to permit assessment of allograft function during a 6-hour postreperfusion period. Allograft gas exchange (every 15 minutes) and hemodynamics (every 60 minutes) were assessed. Peripheral blood PMN CD11b expression was determined by flow cytometry. After sacrifice allograft bronchoalveolar lavage fluid PMN count and allograft tissue myeloperoxidase activity were measured. Two groups were studied: In group I (n = 8) lidocaine hydrochloride was added to the donor flush (20 mg/L) solution. In addition lidocaine was given to the recipient at the time of thoracotomy (intravenous bolus of 4 mg/kg) followed by a continuous infusion of 4 mg/kg/h during implantation and the assessment period. Three dogs that did not reach effective lidocaine blood levels at the time of reperfusion (3 to 4 micrograms/mL) were excluded from analysis. Group II animals (n = 5) received no lidocaine.', 'Gas exchange in group I was superior throughout the assessment period (p < 0.05). Bronchoalveolar lavage fluid PMN count in group I was reduced (0.36 x 10(6)PMN/mL versus 6.2 x 10(6) PML/mL; p < 0.03). Group I allograft myeloperoxidase activity was 0.17 U/mg/min compared with 0.28 U/mg/min in group II (p < 0.01). In lidocaine-treated animals PMN CD11b expression was maintained at basal levels 2 hours after reperfusion, compared with group II, in which upregulation of CD11b was observed. Lower lobe wet/dry ratio was not different in the two groups.']
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['Children with developmental coordination disorder (DCD) struggle to learn new motor skills, demonstrating more variable performance than typically developing (TD) children. The purpose of this study was to determine whether patterns of brain activity differed between children with and without DCD while performing a motor task.', 'Using functional MRI, we measured brain activation patterns in 7 children with DCD and 7 age-matched peers (aged 8-12 years) during a fine-motor, trail-tracing task.', 'Despite similar levels of behavioral motor performance, different patterns of brain activity were noted between the 2 groups. The group with DCD showed significantly more activation than control subjects in left inferior parietal lobule, right middle frontal gyrus, right supramarginal gyrus, right lingual gyrus, right parahippocampal gyrus, right posterior cingulate gyrus, right precentral gyrus, right superior temporal gyrus, and right cerebellar lobule VI. These results suggest that the group with DCD relied on visuospatial processing to complete the task. The TD group demonstrated significantly more activation than the group with DCD in left precuneus, left superior frontal gyrus, right superior temporal gyrus/insula, left inferior frontal gyrus, and left postcentral gyrus; these regions have been associated with spatial processing, motor control and learning, and error processing.']
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['Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes.', 'We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women.', 'We identified 600 iron-deficient (serum ferritin ≤12 μg/L) pregnant women, aged 18-45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 μg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 μg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes.', 'There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 μg/L; 95% CI: 49.5, 58.8 μg/L), and serum hepcidin (14.0 μg/L; 95% CI: 12.4, 15.6 μg/L) and decreases in sTfR (-1.7 mg/L; 95% CI: -2.0, -1.3 mg/L) and ZPP (-17.8 mmol/L; 95% CI: -32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline - up to 12.1 g/L and 14.5 μg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76).']
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['Toll-like receptor (TLR) activity within gestation-associated tissues might have a role in normal pregnancy progression as well as adverse obstetric outcomes such as preterm birth (PTB).', 'The expression and activity of TLRs 1-9 in placentas collected following preterm vaginal delivery after infection-associated preterm labour (IA-PTL) at 25-36 weeks of gestation (preterm-svd, n\xa0=\xa010) were compared with those obtained after normal vaginal delivery at term (term-laboured; n\xa0=\xa017). Placental explants were cultured in the presence of agonists for TLR2, 3, 4, 5, 7, 8 and 9 and cytokine production after 24\xa0h examined. Expression of TLR transcripts was determined using real time quantitative PCR.', 'Reactivity to all agonists except CpG oligonucleotides was observed indicating that other than TLR9 all of the receptors studied yielded functional responses both term and preterm. Significantly less TNFα and IL-6, but not IL-10, were produced by preterm than term samples in response to all TLR agonists. Changes in TLR mRNA expression did not underlie functional differences in the preterm and term groups; nor does a pre-exposure/tolerance model mimic this finding. While glucocorticoids suppressed cytokine production in an in\xa0vitro model using term tissue the association between lower gestational age and decreased cytokine outputs suggests a temporally regulated response.']
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['Very-low-birth-weight (VLBW) infants are occasionally treated with opiates for sedation and pain relief.', 'To study the short term outcomes of VLBW infants treated with opiates.', 'We conducted a retrospective study of all VLBW infants born during the period 2006-2010; 45 were treated with opiates (41 fentanyl continuous IV drip and 4 IV morphine prn); 114 served as controls.', 'In the univariate analysis, VLBW infants treated by opiates had significantly lower Gestational Age (GA) (28.3 ± 2.4 vs. 30.3 ± 2.1 weeks) and BW (1012 ± 299 vs. 1204 ± 219 grams] and required longer periods of ventilatory support (30.3 ± 21.0 vs. 7.7 ± 12.0 days) and oxygen supplementation (40.4 ± 40.3 vs. 7.7 ± 17.3 days). They had significantly more intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA), late onset infections, necrotizing enterocolitis (NEC and bronchopulmonary dysplasia (BPD). Time to reach full enteral (32.5 ± 22.1 vs. 15.6 ± 6.1 days) and full oral (64.6 ± 25.0 vs. 42.0 ± 20.7 days) feedings and length of stay (89.6 ± 37.1 vs. 53.7 ± 20.8 days) were significantly longer. In multivariate analysis, after controlling for GA and BW, opiates remained significantly associated only with PDA and longer ventilatory support and time to full enteral feeding.']
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['Previous research has suggested a trade-off between the capacity of plants to downregulate their phosphorus (P) uptake capacity and their efficiency of P resorption from senescent leaves in species from P-impoverished environments.', 'To investigate this further, four Australian native species (Banksia attenuata, B. menziesii, Acacia truncata and A. xanthina) were grown in a greenhouse in nutrient solutions at a range of P concentrations [P]. Acacia plants received between 0 and 500 µm P; Banksia plants received between 0 and 10 µm P, to avoid major P-toxicity symptoms in these highly P-sensitive species.', 'For both Acacia species, the net P-uptake rates measured at 10 µm P decreased steadily with increasing P supply during growth. In contrast, in B. attenuata, the net rate of P uptake from a solution with 10 µm P increased linearly with increasing P supply during growth. The P-uptake rate of B. menziesii showed no significant response to P supply in the growing medium. Leaf [P] of the four species supported this finding, with A. truncata and A. xanthina showing an increase up to a saturation value of 19 and 21 mg P g(-1) leaf dry mass, respectively (at 500 µm P), whereas B. attenuata and B. menziesii both exhibited a linear increase in leaf [P], reaching 10 and 13 mg P g(-1) leaf dry mass, respectively, without approaching a saturation point. The Banksia plants grown at 10 µm P showed mild symptoms of P toxicity, i.e. yellow spots on some leaves and drying and curling of the tips of the leaves. Leaf P-resorption efficiency was 69 % (B. attenuata), 73 % (B. menziesii), 34 % (A. truncata) and 36 % (A. xanthina). The P-resorption proficiency values were 0·08 mg P g(-1) leaf dry mass (B. attenuata and B. menziesii), 0·32 mg P g(-1) leaf dry mass (A. truncata) and 0·36 mg P g(-1) leaf dry mass (A. xanthina). Combining the present results with additional information on P-remobilization efficiency and the capacity to downregulate P-uptake capacity for two other Australian woody species, we found a strong negative correlation between these traits.']
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['Several studies have demonstrated the prognostic utility of absolute lymphocyte count (ALC) during therapy for a range of malignancies, with low ALC associated with adverse outcome. Here we investigated whether ALC retained independent prognostic significance with respect to minimal residual disease (MRD) status in children with acute lymphoblastic leukemia (ALL).', "We reviewed 171 cases of pediatric ALL treated on the Children's Oncology Group P9900 series of treatment trials. Variables analyzed included ALC at several time points during Induction, age at diagnosis, cytogenetics, initial white blood cell count, and MRD status at Day 29 of Induction (MRD-29).", 'We found high ALC at Induction Day 29 (ALC-29) to be an independent, clinically significant predictor of improved relapse-free and overall survival (OS). Patients with ALC-29 >1,500 cells/µl had a superior 6-year relapse-free survival (80 ± 4% vs. 62 ± 8%, P = 0.018) and overall survival (96 ± 2% vs. 74 ± 8%, P = 0.001). Moreover, ALC-29 identified distinct prognostic subgroups within cases stratified by MRD-29. In subjects with >0.01% MRD, ALC-29 > or <1,500 cells/µl had a significant 51% difference in 6-year OS (92 ± 7% vs. 41 ± 16%, P = 0.0001).']
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['Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy.', 'The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen.', 'Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity.']
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['Black men with prostate cancer are diagnosed at a younger age, present with more aggressive disease, and experience higher mortality. We sought to assess pathological features and biochemical recurrence (BCR) in young men undergoing radical prostatectomy (RP) to determine if there is a difference between black and white men closer to the time of disease initiation.', 'We identified 551 white and 99 black men at a tertiary cancer center who underwent RP at ≤50 years of age. Baseline and pathological features were compared between the two groups. Cox proportional hazards models were utilized to examine the association of race and BCR, and Kaplan-Meier curves were generated to determine biochemical recurrence-free survival (bRFS).', 'There were no differences in median age at surgery, biopsy Gleason score, or comorbidity. Black men had higher preoperative PSA (6.1 ng/ml vs 4.7 ng/ml, p = 0.004), but a greater percentage were cT1c (78% vs 63%), compared to white men. On multivariate analysis, black men demonstrated significantly lower odds of non-organ confined disease (OR 0.39; 95% CI: 0.18, 0.81; p = 0.01) and extracapsular extension (ECE) (OR 0.38; 95% CI: 0.18, 0.81, p = 0.01), and had no difference in Gleason score upgrading and seminal vesicle invasion compared to white men. There was no significant difference in bRFS in men with organ-confined disease; however, among men with locally advanced disease black men trended towards greater BCR (p = 0.052). Black men had 2-year bRFS of 56% vs 75% in white men.']
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['Clinical gene therapy trials using standard Ad5-based vectors have thus far demonstrated limited efficacy, most likely due to low expression levels of adenoviral receptors on tumor cells. We sought to analyze adenoviral receptor expression levels on primary head and neck squamous cell carcinoma (HNSCC) cells and to determine whether adenoviral retargeting to the CD46 receptor via the Ad5/35 system would increase therapeutic potential for HNSCC.', 'We used flow cytometric analyses to determine adenoviral receptor expression levels on nine primary HNSCC cells collected from cancer patients. Adenoviruses Ad5.LacZ and Ad5/35.LacZ were used to analyze the differences in viral transduction both in vitro and in a HNSCC tumor mouse model.', 'Flow cytometric analyses demonstrated uniformly high CD46 expression in all cells studied (85-99%). In contrast, coxsackievirus and adenovirus receptor (CAR) expression was substantially lower and highly variable (1.6-62%). Alpha(v) integrin expression was between 39-98%. In situ stainings for beta-galactosidase gene expression demonstrated that Ad5/35.LacZ was clearly more effective than Ad5.LacZ in transducing primary HNSCC cells. Quantification of beta-galactosidase expression revealed up to 65 times higher transgene expression from Ad5/35.LacZ than Ad5.LacZ. In vivo, beta-galactosidase expression was detected in a substantial area after a single intratumoral injection of Ad5/35.LacZ, whereas injection with Ad5.LacZ resulted in gene expression only in a few cells.']
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['Cdx2 is critical in intestinal proliferation and differentiation. Modulation of Cdx2 function in response to cellular signaling is to be elucidated. We hypothesize that phosphorylation of the Cdx2 activation domain can modulate its function.', 'The Cdx2 activation domain was delineated in transient transfections using different portions of Cdx2 fused to the Gal4-DNA binding domain. In vivo phosphorylation was studied by metabolic labeling with (32)P-orthophosphate. To study a potential phosphorylation site, polyclonal antibodies were generated: CNL was raised against amino acids 54-66 of Cdx2 and P-Cdx2-S60 against the same epitope in which serine 60 was phosphorylated.', 'A critical region for transactivation resides within amino acids 60-70. Substitution of serine 60 with alanine reduces incorporation of (32)P-orthophosphate substantially. S60-phosphorylation decreases Cdx2 transactivation. Phosphorylation of serine 60 can be inhibited with the mitogen-activated protein kinase inhibitors PD98059 or UO126. P-Cdx2-S60 recognizes phosphorylated serine 60 mainly in proliferative compartment of the intestinal epithelial layer. In contrast, CNL recognizes Cdx2 predominantly in the differentiated compartment.']
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['Home blood pressure (HBP) measurements are known as an important adjunct to office blood pressure (OBP) measurements in clinical practice. But little is known about the relationship between HBP and subclinical target organ damage (TOD) other than left ventricular hypertrophy (LVH). So we investigated the relationship of HBP measurements with subclinical TOD in untreated hypertensive patients.', 'We measured ambulatory blood pressure (ABP), HBP and OBP of 93 untreated hypertensive patients (men: 60 and women: 33, mean age, 49±13 years). The ABP was recorded for 24 hours, HBP was measured for one week, and OBP was measured at least in two visits. All BP measurements were taken using automatic BP measuring device. The parameters indicating subclinical TOD were the left-ventricular mass index (LVMI) by transthoracic echocardiography, urinary albumin excretion rate (AER), brachial ankle pulse-wave velocity (PWV), and carotid intima-media thickness (IMT).', 'The LVMI was significantly correlated with systolic HBP and 24 hours systolic ABP, but not with OBP. The AER, PWV and IMT were also significantly correlated with systolic HBP and 24 hours systolic ABP. In a binary logistic regression analysis, systolic HBP, 24 hours systolic and diastolic ABP were the predictors of LVMI, AER and PWV (all p<0.05).']
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['To explore the mechanisms by which liver-infiltrating T lymphocytes cause hepatocyte damage in the liver injury induced by delayed-type hypersensitivity to picryl chloride.', 'Nonparenchymal cells (NPC) were isolated 12 h after liver injury elicitation and fractionated into Kupffer cell-enriched (Fr. A) and lymphocyte-enriched populations (Fr. B). They were used as the effectors for coculture with hepatocytes.', 'The cells in total NPC and Fr. B harvested at 12 h of liver injury were increased two- and six-fold respectively compared with those at 0 h. Fr. B, mainly including CD4+ and CD8+ T cells, exhibited a significantly stronger hepatotoxicity than total NPC did, while Fr.A did not. NPC at 12 h showed remarkably increased matrix metalloproteinase-2 and -9 activities indicative of infiltration potential through extracellular matrix. When NPC and hepatocytes were cultured in separated compartments in Transwell chamber, no hepatotoxicity was observed. However, 30 min-pre-contact with hepatocytes as stimulator significantly triggered NPC hepatotoxicity. The acquisition of such hepatotoxic potential was significantly abolished by anti-LFA-1 pretreatment for NPC or anti-ICAM-1 treatment for hepatocytes before contact. Both aprotonin and superoxide dismutase dose-dependently inhibited the hepatotoxicity.']
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['Diabetes is an established risk factor for complications following total joint arthroplasty. However, the correlation between postoperative blood glucose and preoperative hemoglobin A1C levels with complications following total joint arthroplasty is not well described.', 'All patients undergoing elective primary total joint arthroplasty at our institution from 2004 through 2011 with both postoperative blood glucose and preoperative hemoglobin A1C levels were identified in a retrospective review. From among 1702 patients, those with wound complications within thirty days after the index arthroplasty were identified. A control group matched for exact age, sex, procedure, tourniquet use, surgical approach, and use of antibiotic cement was also created. Thirty patients met the study group inclusion criteria. The mean patient age was seventy-two years (range, fifty-three to eighty-nine years); the majority (53%) of patients were female.', 'The odds ratio for developing a wound complication was 3.75 (95% confidence interval, 1.25 to 11.22; p = 0.02) in patients with a mean postoperative glucose of >200 mg/dL, 3.0 (95% confidence interval, 0.97 to 9.30; p = 0.08) in patients with a maximum postoperative blood glucose of >260 mg/dL, and 9.0 (95% confidence interval, 1.14 to 71.20; p = 0.03) in patients with a preoperative hemoglobin A1C value of >6.7%.']
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['Using high-resolution structural MRI, we endeavored to study the relationships among APOE ε4, hippocampal subfield and stratal anatomy, and episodic memory.', 'Using a cross-sectional design, we studied 11 patients with Alzheimer disease dementia, 14 patients with amnestic mild cognitive impairment, and 14 age-matched healthy controls with no group differences in APOE ε4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI targeted to the hippocampus and neuropsychological assessment.', 'We found a selective, dose-dependent association of APOE ε4 with greater thinning of the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1-SRLM), a hippocampal subregion known to exhibit early vulnerability to neurofibrillary pathology in Alzheimer disease. The relationship between the ε4 allele and CA1-SRLM thinning persisted after controlling for dementia severity, and the size of other hippocampal subfields and the entorhinal cortex did not differ by APOE ε4 carrier status. Carriers also exhibited worse episodic memory function but similar performance in other cognitive domains compared with noncarriers. In a statistical mediation analysis, we found support for the hypothesis that CA1-SRLM thinning may link the APOE ε4 allele to its phenotypic effects on memory.']
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['The anaesthetic potency of intravenous propofol is quantified by its Cp50 value, which is defined as the plasma concentration required to prevent movement response in 50% of patients to surgical stimuli. We hypothesised that, in addition to propofol anaesthesia, an intravenous bolus of lidocaine 1.5\u2009mg/kg will decrease the Cp50 value of propofol during anaesthesia.', "We enrolled 54 elective surgical patients undergoing propofol-based anaesthesia, and randomised them to either lidocaine 1.5\u2009mg/kg, lidocaine 0.5\u2009mg/kg or placebo (NaCl 0.9%) 3\u2009min before skin incision. The propofol Cp50 value was then calculated using the 'up-and-down' method of Dixon and Massey.", 'There was no significant reduction in propofol requirements after the administration of 0.5\u2009mg/kg lidocaine from 8.5\u2009μg/ml [confidence interval (CI) 6.0-11.625] to 8.25\u2009μg/ml (CI 6.75-9.76); however, a bolus of 1.5\u2009mg/kg lidocaine decreased the Cp50 value of propofol by 42% from 8.5\u2009μg/ml (CI 6.0-11.625) to 4.92\u2009μg/ml (CI 4.5-5.78) (P\u2009<\u20090.05).']
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['Dietary fiber shortens gut transit time, but data on the effects of fiber components (including resistant starch, RS) on intestinal contractility are limited. We have examined RS effects in male Sprague-Dawley rats fed either a high-amylose maize starch (HAMS) or a wholemeal made from high-amylose wheat (HAW) on ileal and colonic contractility ex vivo and expression of genes associated with smooth muscle contractility.', 'Rats were fed diets containing 19 % fat, 20 % protein, and either low-amylose maize starch (LAMS), HAMS, wholemeal low-amylose wheat (LAW) or HAW for 11 week. Isolated ileal and proximal colonic sections were induced to contract electrically, or by receptor-independent (KCl) or receptor-dependent agents. Colonic gene expression was assessed using an Affymetrix microarray.', 'Ileal contractility was unaffected by treatment. Maximal proximal colonic contractility induced electrically or by angiotensin II or carbachol was lower for rats fed HAMS and LAW relative to those fed LAMS (P < 0.05). The colonic expression of genes, including cholinergic receptors (Chrm2, Chrm3), serotonin receptors (Htr5a, Htr7), a protease-activated receptor (F2r), a prokineticin receptor (Prokr1), prokineticin (Prok1), and nitric oxide synthase 2 (Nos2), was altered by dietary HAMS relative to LAMS (P < 0.05). HAW did not significantly affect these genes or colonic contractility relative to effects of LAMS.']
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['Unnecessary prescribing of antibiotics is a major public health concern. General practitioners (GPs) prescribe most antibiotics, often for upper respiratory tract infections (URTIs), and have in general been shown to prescribe antibiotics more often to women. No studies have examined the influence of patient gender on unnecessary antibiotic prescribing.', 'To study a possible gender difference in unnecessary antibiotic prescriptions for URTIs in general practice; to assess whether a possible difference is explained by patient demand for antibiotics.', 'Post-hoc analysis of a cross-sectional study including 15,022 patients with URTI (acute rhinitis, acute otitis media, acute sinusitis, acute pharyngotonsillitis) from Argentina, Denmark, Lithuania, Russia, Spain and Sweden (HAPPY AUDIT Project). The association between gender and unnecessary antibiotic prescriptions, unadjusted and adjusted for treatment demand, was analysed using logistic regression models.', 'A total of 25% of patients with URTI received antibiotics; in 45% of the cases, antibiotics were unnecessary. Overall, no gender difference for unnecessary prescribing of antibiotics for URTIs was found. Women with acute otitis media received an unnecessary antibiotic twice as often as men (14.4% versus 7.1%). In Danish patients with acute pharyngotonsillitis, there was a gender difference in unnecessary prescriptions for antibiotics (women 29.1% versus men 48.6%). Some 14% of patients receiving unnecessary antibiotics demonstrated a demand for antibiotics, but no gender difference was found in this group.']
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['The World Health Organization (WHO) has published "Guidelines on Hand Hygiene in Health Care" recommending 2 hand rub formulations based on 80% vol/vol ethanol or 75% vol/vol isopropanol for local production in healthcare settings where commercial products are not available or are too expensive. Previous investigations have shown that neither formulation meets the efficacy requirements of European norm (EN) 12791, which is the most stringent available norm for surgical hand rub preparations. Even when modified with approximately 5% higher alcohol content, the formulations proved to be inferior to the reference of the norm when measured after 3 hours.', 'Because the high glycerol content of the formulations was suspected to negatively influence their efficacy, additional investigations were performed with varying glycerol content.', "Modified formulations with higher alcohol concentration (mass instead of volume percentage) and lower glycerol concentration (0.725% instead of 1.45%) or without the addition of glycerol were evaluated for their conformity with the efficacy requirements of EN 12791, which demands noninferiority in comparison with a reference hand antisepsis procedure immediately and 3 hours after treatment on volunteers' hands.", 'Randomized Latin-square design.', 'Microbiology laboratory of the Medical University of Vienna, Vienna, Austria.', 'Twenty-five healthy volunteers.', 'Reducing the concentration of glycerol or omitting it completely rendered both WHO formulations noninferior to the reference, both immediately and 3 hours after surgical hand antisepsis.']
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['Dietary supplementation with ursolic acid (UA) prevents monocyte dysfunction in diabetic mice and protects mice against atherosclerosis and loss of renal function. The goal of this study was to determine the molecular mechanism by which UA prevents monocyte dysfunction induced by metabolic stress.', 'Metabolic stress sensitizes or "primes" human THP-1 monocytes and murine peritoneal macrophages to the chemoattractant MCP-1, converting these cells into a hyper-chemotactic phenotype. UA protected THP-1 monocytes and peritoneal macrophages against metabolic priming and prevented their hyper-reactivity to MCP-1. UA blocked the metabolic stress-induced increase in global protein-S-glutathionylation, a measure of cellular thiol oxidative stress, and normalized actin-S-glutathionylation. UA also restored MAPK phosphatase-1 (MKP1) protein expression and phosphatase activity, decreased by metabolic priming, and normalized p38 MAPK activation. Neither metabolic stress nor UA supplementation altered mRNA or protein levels of glutaredoxin-1, the principal enzyme responsible for the reduction of mixed disulfides between glutathione and protein thiols in these cells. However, the induction of Nox4 by metabolic stress, required for metabolic priming, was inhibited by UA in both THP-1 monocytes and peritoneal macrophages.']
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['Liver regeneration is inhibited in small-for-size grafts, which plays a role in the failure of partial liver grafts after transplantation. The Wnt/β-catenin signaling pathway plays a critical role in liver development, regeneration and homeostasis. In this study, we investigated whether pharmacological activation of Wnt signaling improves liver regeneration after small-for-size liver transplantation.', 'The livers of male Sprague-Dawley rats were reduced to approximately 50% and 30% of their original sizes and transplanted. A Wnt agonist (2-amino-4-[3,4-[methylenedioxy]benzylamino]-6-[3-methoxyphenyl] pyrimidine], 5\u2009mg/kg bodyweight) or an equal volume of vehicle was administrated i.p. into the donor 1\u2009h before the transplantation. Tissue and blood samples were collected at various times after transplantation, and a survival study was performed.', 'Hepatic expression of active β-catenin and its downstream target gene Axin2 were decreased in 30% of liver grafts after transplantation while the Wnt agonist increased their expression similar to the 50% liver grafts. The Wnt agonist reversed inhibition of cyclin D1 expression and adenosine triphosphate production in the 30% liver grafts compared with the 50% grafts. The Wnt agonist also attenuated hepatocellular injury and increased the hepatocyte proliferation response, liver regeneration rate and survival after transplantation of the 30% liver graft.']
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['Motor cortex excitability can be measured by transcranial magnetic stimulation (TMS) using different coil types, but paired-TMS was originally devised with a figure-of-eight coil. We asked whether the most popular, circular coil was suited to the every-day assessment of cortical excitability, particularly paired-TMS indexes, and if it reduced the measurement error.', 'We studied 12 right-handed, healthy subjects (34±7.6 years). Resting motor threshold (MT), cortical silent period (CSP), short-interval intracortical inhibition (SICI) at the 2, 3, 4 and 5 ms interstimulus intervals (ISIs) and intracortical facilitation (ICF) at the 14 and 16 ms ISIs were measured. Intrinsic variability of these indexes was evaluated in terms of Coefficients of Variation, to estimate the measurement error. This sequence was carried out both using a figure-of-eight coil over the hand motor area and a circular coil centred at the vertex. Testing was repeated 8-13 months later.', 'On average, MT, SICI and ICF did not show any statistically significant difference (p>0.05) when studied with the figure-of-eight as compared with the circular coil. CSP was significantly shorter (p=0.007) with the figure-of-eight coil. Using either coil did not affect measurement variability. There was no significant session-to-session group difference at any of the variables using either coil type.']
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['The aim of the study was to determine the molecular mechanisms underlying the quasi-equilibrium between HIV and its host in the model of functional cure represented by elite controllers who spontaneously maintain exceptionally low levels of HIV reservoirs.', 'Whole-genome transcriptional study and quantification of the cell-associated HIV DNA and HIV RNA levels of the four major resting CD4 T-cell subsets in HIV-1-infected elite controllers, viremic long-term nonprogressors (vir-LTNPs), and uninfected individuals.', 'We compared the whole-genome transcriptional profiles (ArrayExpress accession number E-MTAB-1480) of the four major resting CD4 T-cell subsets [naive (TN), central-memory (TCM), transitional-memory (TTM), and effector-memory (TEM)] from 14 HIV-1-infected individuals including seven elite controllers (E-LTNPs) and seven vir-LTNPs, and from seven uninfected individuals. The HIV-1 cellular DNA and mRNA levels were quantified in parallel in each sorted subset.', 'Host gene transcriptomes followed subset differentiation and viremia except in E-LTNPs wherein TCM, the main CD4 cell compartment, showed the highest activity with three specific signatures involving overexpression of T-cell receptor and costimulation signaling pathways, overexpression of the PRDM-1/Blimp-1 transcriptional repressor, and downmodulation of type-I IFN-related genes. Among subsets, the PRDM1/Blimp-1 upregulation was associated with lower levels of both cellular HIV-DNA and HIV mRNA levels.']
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['Hyperglycemia-induced reactive oxygen species (ROS) production plays a major role in the pathogenesis of diabetic vascular dysfunction. However, the underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a key component of innate immunity, is known to be activated during diabetes. Therefore, we hypothesize that hyperglycemia activates TLR4 signaling in vascular smooth muscle cells (VSMCs) that triggers ROS production and causes vascular dysfunction. Rat mesenteric VSMCs exposed to high glucose (25 mmol/l) increased TLR4 expression and activated TLR4 signaling via upregulation of myeloid differentiation factor 88 (MyD88). TLR4 inhibitor CLI-095 significantly attenuated elevated levels of ROS and nuclear factor-kappa B (NF-κB) activity in VSMCs exposed to high glucose. Mesenteric arteries from streptozotocin-induced diabetic rats treated with CLI-095 (2 mg/kg/day) intraperitoneally for 2 weeks exhibited reduced ROS generation and attenuated noradrenaline-induced contraction. These results suggest that hyperglycemia-induced ROS generation and NF-κB activation in VSMCs are at least, in part, mediated by TLR4 signaling. Therefore, strategies to block TLR4 signaling pathways pose a promising avenue to alleviate diabetic-induced vascular complications.']
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['Traumatic hemorrhagic shock resulting in tissue hypoxia is a significant cause of morbidity and mortality in polytraumatized patients. Early identification of tissue hypoxia is possible with microdialysis. The aim of this study was to determine the correlation between a marker of tissue hypoxia (L/P; lactate to pyruvate ratio) and selected parameters of systemic oxygen delivery (Hb; hemoglobin) and oxygen extraction (ScvO2; central venous oxygen saturation). We also investigated the severity of tissue hypoxia over the course of care.', 'Adult patients with traumatic hemorrhagic shock were enrolled in this prospective, observational study. Microdialysis of the peripheral muscle tissue was performed. Demographic data and timeline of care were collected. Tissue lactate, pyruvate, glycerol, glucose levels, hemoglobin, serum lactate and oxygen saturation of the central venous blood (ScvO2) levels were also measured.', 'The L/P ratio trend may react to changes in systemic hemoglobin levels with a delay of 7 to 10 hours, particularly when systemic hemoglobin levels are increased by transfusion. Decrease in tissue L/P ratio may react to increase in ScvO2 with a delay of up to 10 hours, and such a decrease may signify elimination of tissue hypoxia after transfusion. We also observed changes in the L/P trend in the 13 hours preceding a change in the hemoglobin level. Fluid administration, which is routinely used as a first-line treatment of hypovolemic shock, can cause hemodilution and decreased hemoglobin. When ScvO2 decreases, increase in L/P ratio may precede the ScvO2 trend by 10 or 11 hours. An increase in the L/P ratio is an early warning sign of insufficient tissue oxygenation and should lead to intensive observation of hemoglobin levels, ScvO2 and other hemodynamic parameters. Patients who were treated more rapidly had lower maximal L/P values and a lower degree of tissue ischemia.']
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["SAL (SALLRSIPA) is a peptide fragment of activity-dependent neurotrophic factor. Both L- and D-SAL diminish ethanol's pathogenesis, however, the D-peptide is protease resistant, and can therefore be effectively administered in a diet. The present study tested the hypothesis that D-SAL provided in a liquid diet containing ethanol will prevent ethanol-induced teratogenicity in mice.", 'Following an ethanol acclimation period, female C57Bl/6J mice were withdrawn from the ethanol, bred, and then returned during gestational days (GD) 7 and 8 to a control liquid diet or one containing 4.8% ethanol alone or in combination with 5.6 microg/ml D-SAL. At these doses, the mice received approximately 75 microg of D-SAL on each day and achieved peak blood-alcohol concentrations on GD 8 that ranged from 148-162 mg/dl. On GD 14, the fetuses were examined for the presence of ocular abnormalities including microphthalmia and irregularly shaped pupils, teratogenic effects known to result from this ethanol exposure paradigm.', 'Dietary D-SAL reduced the incidence of ocular defects in ethanol-exposed fetuses from 29 to 10% in the right eyes and from 21 to 7.5% in the left eyes; levels similar to those observed in pair-fed controls. In addition to decreasing their incidence, D-SAL also reduced the severity of the ocular defects.']
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