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['Investigate whether high-quality chronic care delivery improved the experiences of patients.', 'This study had a longitudinal design.', 'We surveyed professionals and patients in 17 disease management programs targeting patients with cardiovascular diseases, chronic obstructive pulmonary disease, heart failure, stroke, comorbidity and eating disorders.', "Patients completed questionnaires including the Patient Assessment of Chronic Illness Care (PACIC) [T1 (2010), 2637/4576 (58%); T2 (2011), 2314/4330 (53%)]. Professionals' Assessment of Chronic Illness Care (ACIC) scores [T1, 150/274 (55%); T2, 225/325 (68%)] were used as a context variable for care delivery. We used two-tailed, paired t-tests to investigate improvements in chronic illness care quality and patients' experiences with chronic care delivery. We employed multilevel analyses to investigate the predictive role of chronic care delivery quality in improving patients' experiences with care delivery.", "Overall, care quality and patients' experiences with chronic illness care delivery significantly improved. PACIC scores improved significantly from 2.89 at T1 to 2.96 at T2 and ACIC-S scores improved significantly from 6.83 at T1 to 7.18 at T2. After adjusting for patients' experiences with care delivery at T1, age, educational level, marital status, gender and mental and physical quality of life, analyses showed that the quality of chronic care delivery at T1 (P < 0.001) and changes in care delivery quality (P < 0.001) predicted patients' experiences with chronic care delivery at T2."]

['Spatially resolved near-infrared spectroscopy-determined frontal lobe tissue oxygenation (ScO2) is reduced with administration of phenylephrine, while cerebral blood flow may remain unaffected. We hypothesized that extracranial vasoconstriction explains the effect of phenylephrine on ScO2.', 'We measured ScO2 and internal and external carotid as well as vertebral artery blood flow in 7 volunteers (25 [SD 4] years) by duplex ultrasonography during IV infusion of phenylephrine, together with middle cerebral artery mean blood velocity, forehead skin blood flow, and mean arterial blood pressure.', 'During phenylephrine infusion, mean arterial blood pressure increased, while ScO2 decreased by -19% ± 3% (mean ± SE; P = 0.0005). External carotid artery (-27.5% ± 3.0%) and skin blood flow (-25.4% ± 7.8%) decreased in response to phenylephrine administration, and there was a relationship between ScO2 and forehead skin blood flow (Pearson r = 0.55, P = 0.042, 95% confidence interval [CI], = 0.025-0.84; Spearman r = 0.81, P < 0.001, 95% CI, 0.49-0.94) and external carotid artery conductance (Pearson r = 0.62, P = 0.019, 95% CI, 0.13 to 0.86; Spearman r = 0.64, P = 0.012, 95% CI, 0.17-0.88).']

["Research published in Circulation has shown that cardiac mortality is highest during December and January. We investigated whether some of this spike could be ascribed to the Christmas/New Year's holidays rather than to climatic factors.", "We fitted a locally weighted polynomial regression line to daily mortality to estimate the number of deaths expected during the holiday period, using the null hypothesis that natural-cause mortality is unaffected by the Christmas/New Year's holidays. We then compared the number of deaths expected during the holiday period, given the null hypothesis, with the number of deaths observed. For cardiac and noncardiac diseases, a spike in daily mortality occurs during the Christmas/New Year's holiday period. This spike persists after adjusting for trends and seasons and is particularly large for individuals who are dead on arrival at a hospital, die in the emergency department, or die as outpatients. For this group during the holiday period, 4.65% (+/-0.30%; 95% CI, 4.06% to 5.24%) more cardiac and 4.99% (+/-0.42%; 95% CI, 4.17% to 5.81%) more noncardiac deaths occur than would be expected if the holidays did not affect mortality. Cardiac mortality for individuals who are dead on arrival, die in the emergency department, or die as outpatients peaks at Christmas and again at New Year's. These twin holiday spikes also are conspicuous for noncardiac mortality. The excess in holiday mortality is growing proportionately larger over time, both for cardiac and noncardiac mortality."]

['To test the hypothesis that recurrent sleep curtailment will result in decreased physical activity in adults at risk for type 2 diabetes.', 'Two-condition 2-period randomized crossover study.', 'University General Clinical Research Center.', 'Eighteen healthy patients with parental history of type 2 diabetes (9 females and 9 males, age 27 yr [standard deviation 3], body mass index 23.7 [2.3] kg/m²).', 'Two week-long inpatient sessions with 8.5 or 5.5-hr nighttime sleep opportunity. Participants who exercised regularly (39%) could follow their usual exercise routines during both sessions.', 'Sleep and total body movement were measured by wrist actigraphy and waist accelerometry. Subjective mood and vigor was assessed using visual analog scales. The main outcome was the comparison of total activity counts between sleep conditions. Ancillary endpoints included changes in sedentary, light, and moderate plus vigorous activity, and their association with changes in mood and vigor. Daily sleep was reduced by 2.3 hr (P < 0.001) and total activity counts were 31% lower (P = 0.020) during the 5.5-hr time-in-bed condition. This was accompanied by a 24% reduction in moderate-plus-vigorous activity time (P = 0.005) and more sedentary behavior (+21 min/day; P = 0.020). The decrease in daily activity during the 5.5-hr time-in-bed condition was seen mostly in participants who exercised regularly (-39 versus -4% in exercisers versus nonexercisers; P = 0.027). Sleep loss-related declines in physical activity correlated strongly with declines in subjective vigor (R = 0.90; P < 0.001).']

['Prior studies have demonstrated that endoscopists\' estimates of polyp size are imprecise. The aim of this study was to determine whether a modified polypectomy "ruler snare" improves the accuracy of assessment of polyp size in real time without the use of additional devices.', 'Ten artificial polyps of predetermined sizes (4 to 25 mm) were affixed to the inside of a colon model. A standard polypectomy snare was modified by adding 5-mm graduated markings to the distal end of the plastic sheath. Study participants estimated the sizes of the artificial polyps during simulated colonoscopies, first using a standard snare and then with the modified ruler snare.', "Thirty-four private practice and academic gastroenterologists participated in the study. Endoscopists' ability to accurately classify polyps by size (diminutive, small, or large) improved from 48.5% to 60.3% with the ruler snare (P = .002). The greatest improvement in precision was seen among the large polyps, where accuracy increased from 35.9% to 58.2% with use of the ruler snare (P < .0001). Participants underestimated polyp size by a mean of 3.6 mm (interquartile range, -5 to -2 mm) with the standard snare and 1.8 mm (interquartile range, -3 to 0 mm) with the ruler snare, which corresponded to a 44.2% improvement in accuracy with the ruler snare (P < .05)."]

['To propose a new mathematical model to estimate the length of fetal long bones in early pregnancy that can be used in the routine clinical setting.', "In a group of 400 singleton normal fetuses, referred for transvaginal ultrasound examination between 11 and 16 weeks' gestation prior to genetic amniocentesis, a regression analysis was performed to evaluate the relationship between femur length (FLl) (mm) and biparietal diameter (BPD) (mm) and gestational age (GA) (days), as well as between humerus length (HL) (mm) and BPD (mm) and GA (days). The confidence intervals (CIs) of the predicted values for different values of BPD and for different gestational periods and CIs for the regression coefficients are stated as the mean +/- SD of standardized residuals. The accuracy of our best models obtained were evaluated at each gestational week between 11 and 16 with a 10% error cut-off limit.", "The best relationships between FL and HL versus BPD and GA are: expected FL = -16.92108 + 0.4569402 BPD +0.171617 GA (R(2) = 0.86) and expected HL = -16.28531 + 0.4283019 BPD + 0.1696017 GA (R(2) = 0.88), respectively. When a cut-off limit of 10% in estimating fetal long bones was utilized, the mathematical models revealed a good accuracy particularly at 13-14 weeks' gestation, a period when transvaginal biometric and morphologic examination is advisable and the highest percentage of scans are performed."]

['To investigate the effect of the metabolite of leflunomide, A771726,on proliferation and collagen synthesis of hepatic stellate cell (HSC).', 'HSC and Kupffer cells were isolated from the rat liver by collagenase IV and pronase perfusion, and purified by density gradient separation. The effects of A771726 on cell proliferation and collagen synthesis were examined by 3H-thymidine and 3H-proline incorporation assays, respectively. The TGF-beta, TNF-alpha and IL-1 levels in Kupffer cell conditioned medium (KCCM) were determined by enzyme-linked immunosorbent assay (ELISA).', 'HSC and Kupffer cells in rat liver were well separated. The KCCM of CCl4-injured rats had significant stimulation effect on proliferation and collagen synthesis of HSC in primary culture. Addition of A771726 (0.001-10 micromol/Lein HSC culture stimulated by KCCM significantly inhibited proliferation and collagen synthesis of HSC. Furthermore, the elevated TGF-beta, TNF-alpha and IL-1 levels in KCCM of CCl4-injured rats were significantly reduced in A771726 treatment groups.']

['Diet-induced obesity (DIO) in mice causes vascular inflammation and insulin resistance that are accompanied by decreased endothelial-derived NO production. We sought to determine whether reduced NO-cGMP signaling contributes to the deleterious effects of DIO on the vasculature and, if so, whether these effects can be blocked by increased vascular NO-cGMP signaling.', 'By using an established endothelial cell culture model of insulin resistance, exposure to palmitate, 100 micromol/L, for 3 hours induced both cellular inflammation (activation of IKK beta-nuclear factor-kappaB) and impaired insulin signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase pathway. Sensitivity to palmitate-induced endothelial inflammation and insulin resistance was increased when NO signaling was reduced using an endothelial NO synthase inhibitor, whereas endothelial responses to palmitate were blocked by pretreatment with either an NO donor or a cGMP analogue. To investigate whether endogenous NO-cGMP signaling protects against vascular responses to nutrient excess in vivo, adult male mice lacking endothelial NO synthase were studied. As predicted, both vascular inflammation (phosphorylated I kappaB alpha and intercellular adhesion molecule levels) and insulin resistance (phosphorylated Akt [pAkt] and phosphorylated eNOS [peNOS] levels) were increased in endothelial NO synthase(-/-) (eNOS(-/-)) mice, reminiscent of the effect of DIO in wild-type controls. Next, we asked whether the vascular response to DIO in wild-type mice can be reversed by a pharmacological increase of cGMP signaling. C57BL6 mice were either fed a high-fat diet or remained on a low-fat diet for 8 weeks. During the final 2 weeks of the study, mice on each diet received either placebo or the phosphodiesterase-5 inhibitor sildenafil, 10 mg/kg per day orally. In high-fat diet-fed mice, vascular inflammation and insulin resistance were completely prevented by sildenafil administration at a dose that had no effect in mice fed the low-fat diet.']

['Celastrol is one of several bioactive compounds extracted from the medicinal plant Tripterygium wilfordii. Celastrol is used to treat inflammatory conditions, and shows benefits in models of neurodegenerative disease, cancer and arthritis, although its mechanism of action is incompletely understood.', 'Celastrol was tested on human NADPH oxidases (NOXs) using a panel of experiments: production of reactive oxygen species and oxygen consumption by NOX enzymes, xanthine oxidase activity, cell toxicity, phagocyte oxidase subunit translocation, and binding to cytosolic subunits of NOX enzymes. The effect of celastrol was compared with diphenyleneiodonium, an established inhibitor of flavoproteins.', 'Low concentrations of celastrol completely inhibited NOX1, NOX2, NOX4 and NOX5 within minutes with concentration-response curves exhibiting higher Hill coefficients and lower IC₅₀ values for NOX1 and NOX2 compared with NOX4 and NOX5, suggesting differences in their mode of action. In a cell-free system, celastrol had an IC₅₀ of 1.24 and 8.4 µM for NOX2 and NOX5, respectively. Cytotoxicity, oxidant scavenging, and inhibition of p47(phox) translocation could not account for NOX inhibition. Celastrol bound to a recombinant p47(phox) and disrupted the binding of the proline rich region of p22(phox) to the tandem SH3 domain of p47(phox) and NOXO1, the cytosolic subunits of NOX2 and NOX1, respectively.']

['Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Because little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the human afamin gene and performing large-scale human epidemiological studies.', 'Transgenic mice overexpressing afamin revealed increased body weight and serum concentrations of lipids and glucose. We applied a random-effects meta-analysis using age- and sex-adjusted baseline and follow-up investigations in the population-based Bruneck (n=826), Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR; n=1499), and KOoperative Gesundheitsforschung in der Region Augsburg (KORA) F4 studies (n=3060). Mean afamin concentrations were 62.5±15.3, 66.2±14.3, and 70.6±17.2 mg/L in Bruneck, SAPHIR, and KORA F4, respectively. Per 10 mg/L increment in afamin measured at baseline, the number of metabolic syndrome components increased by 19% (incidence rate ratio=1.19; 95% confidence interval [CI], 1.16-1.21; P=5.62×10(-64)). With the same afamin increment used at baseline, we observed an 8% gain in metabolic syndrome components between baseline and follow-up (incidence rate ratio=1.08; 95% CI, 1.06-1.10; P=8.87×10(-16)). Afamin concentrations at baseline were highly significantly related to all individual metabolic syndrome components at baseline and at follow-up. This observation was most pronounced for elevated waist circumference (odds ratio, 1.79; 95% CI, 1.54-2.09; P=4.15×10(-14) at baseline and odds ratio, 1.46; 95% CI, 1.31-1.63; P=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (odds ratio, 1.46; 95% CI, 1.40-1.52; P=1.87×10(-69) and odds ratio, 1.46; 95% CI, 1.24-1.71; P=5.13×10(-6), respectively).']

['Investigation of atrophy data from a pivotal natalizumab trial has demonstrated an increased rate of volume loss, compared to placebo, after the first year of therapy. It was considered to be probably due to a pseudoatrophy effect.', 'To assess grey and white matter volume changes and their relation to global brain volume changes and to baseline inflammation, for patients under natalizumab therapy.', 'We selected 45 patients on natalizumab therapy for at least 24 months, with magnetic resonance imaging (MRI) scans at baseline, 12 and 24 months. We calculated the percentage brain volume change (PBVC) for the first and second year, using SIENA software. Grey and white matter fractions (GMF and WMF, respectively) for the first year were calculated with SPM5, using lesion masks. After quality checks, six patients were excluded. We studied the predictive variables of change in brain volumes.', 'The PBVC decrease was faster during the first year (-1.10% ± 1.43%), as compared to the second (-0.51% ± 0.96%) (p = 0.037). These differences were more marked in patients with baseline gadolinium-enhancing lesions (p = 0.005). Mean GMF and WMF changes during the first year of treatment were +1.15% (n.s.) and -1.72% (p = 0.017), respectively. The presence of active lesions at baseline MRI predicted PBVC (p = 0.022) and WMF change (p = 0.026) during the first year of treatment, after adjusting for age and corticosteroid treatment. No predictors were found for GMF volume changes.']

['The aim of this study was to compare the clinical characteristics of patients enrolled in randomized clinical trials on congestive heart failure treatment with those of real-world patients encountered in daily clinical practice.', 'We searched the Cochrane review methodology, Medline and SilverPlatter databases to obtain the clinical characteristics of both patients enrolled in therapeutic clinical trials and real-world patients with heart failure. We selected 27 clinical trials, and 8 prospective epidemiological studies or registries published between 1987 and 2001 which enrolled 53,859 and 18,207 patients, respectively.', 'On average, compared to real-world heart failure patients, patients enrolled in clinical trials were younger (63 +/- 10 vs 75 +/- 11 years respectively, p < 0.0001), and more likely to be male (72 vs 54% respectively, p < 0.0001). Clinical trial patients showed a lower ejection fraction (26 +/- 7 vs 38 +/- 15% respectively, p < 0.0001) but a lower prevalence of NYHA functional class III-IV (62 vs 75% respectively, p < 0.0001) than real-world patients. In clinical trial patients, the prevalence of ischemic heart disease (67 vs 42% respectively, p < 0.0001) and a history of previous myocardial infarction (62 vs 42% respectively, p < 0.0001) were higher than in real-world patients. Conversely, the prevalence of chronic atrial fibrillation (12 vs 31% respectively, p < 0.0001) and of diabetes (22 vs 24% respectively, p < 0.02) was lower in trial patients than in real-world patients.']

['The association between renal dysfunction and risk of cardiovascular (CV) events and mortality has been reported in several studies. However, it is unclear whether reduction in urinary albumin excretion (UAE) is associated with reduced risk of clinical events. Therefore, we sought to investigate, in a meta-regression analysis of randomized studies enrolling hypertensive and/or diabetic patients, whether changes in UAE are associated with changes in CV outcomes and all-cause mortality.', 'MEDLINE, ISI Web of Science, Cochrane Database and Scopus were searched for randomized trials enrolling more than 200 diabetic and/or hypertensive patients, reporting UAE at baseline and at end of follow-up and CV events [CV death, myocardial infarction (MI), and stroke], as well all-cause mortality.', 'Thirty-two trials enrolling 80,812 participants were included in analyses. Meta-regression analysis showed that each 10% reduction of UAE was significantly associated with 13% reduction of MI (Regression Coefficient [RC]:0.0055; 95% Confidence Interval [CI]:0.0014 to 0.0095; p=0.010), with 29% reduction of stroke (RC:0.0124; CI:0.0030 to 0.0218; p=0.013) and with 14% reduction of the composite outcome (CV death, MI, stroke)(RC:0.0059; CI:0.0027 to 0.0090; p=0.001), whereas not significantly associated with all-cause (RC:0.0028; CI:-0.0047 to 0.0103; p=0.486) and CV mortality (RC:0.0028; CI:-0.0047 to 0.0103; p=0.447). Results were mostly confirmed by sensitivity analysis. No heterogeneity or publication bias was detected.']

['The aim of this study was to assess the role of cyclic variation (CV) of myocardial integrated backscatter (IBS) in the prediction of left ventricular (LV) remodeling in patients with anterior acute myocardial infarction (AMI) after primary coronary angioplasty.', 'Some studies have shown that the CV of myocardial IBS predicts myocardial viability for patients with AMI.', 'We recorded short-axis IBS images within 24 hours of angioplasty in 80 patients with anterior AMI. Two parameters were measured: the magnitude of CV and the normalized time delay (NTD). The increase in LV end-diastolic volume (LVEDV) at 4 weeks (DeltaLVEDV) was defined as LV remodeling (>20% increase from baseline).', 'Patients were divided into two groups according to LV remodeling status: the remodeling group (n = 41) and the nonremodeling group (n = 39). There was a significant difference in the magnitude of CV between the two groups (5.11 +/- 1.47 vs 5.96 +/- 189 dB, P < .05), and the NTD was significantly different in the two groups (1.57 +/- 0.31 vs 1.23 +/- 0.32, P < .0001). The correlation between the magnitude of CV and DeltaLVEDV was significant but weak (r = -0.338, P < .01). There was significant correlation between NTD and DeltaLVEDV (r = 0.443, P < .0001). Using NTD greater than 1.35 as the optimal cutoff, the sensitivity, specificity, and positive and negative predictive values to predict LV remodeling were 82%, 86%, 87%, and 80%, respectively.']

['Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality.', 'We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic.', 'Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state.']

['Conventional treatment for mesothelioma is largely ineffective. We therefore evaluated the novel approach of adenoviral gene transfer of the proapoptotic Bcl-2 family member Bak in mesothelioma cancer cell lines, which are sensitive and resistant to adenoviral p53.', 'Binary adenoviral Bak (Ad/GT-Bak and Ad/GV16) and LacZ (Ad/GT-LacZ and Ad/GV16) vectors were used for transduction of the mesothelioma cell lines I-45 (p53 resistant) and REN (p53 sensitive). Protein levels were determined by Western blotting. Apoptosis was assessed by morphologic changes, caspase-3 cleavage, and fluorescence-activated cell sorter analysis of subdiploid populations. Cell viability was determined with the XTT assay. Statistical analysis was performed with analysis of variance and the Student t test.', 'High levels of Bak gene transfer were seen after coadministration of Ad/GT-Bak and Ad/GV16 in both mesothelioma cell lines. Apoptosis was induced 24 hours after Bak but not LacZ gene transfer ([Bak: I-45, 36%; REN, 25%] vs [LacZ: I-45, 1%; REN, 3%], P <.05]) in p53-sensitive (REN) and p53-resistant (I-45) cell lines. Cellular viability was significantly decreased 48 to 72 hours after Bak gene transfer compared with control vector in both cell lines (72 hours: Bak I-45, 1.4% +/- 1.0%, and Bak REN, 4.7% +/- 1%, vs Lac-Z I-45, 83% +/- 3%, and Lac-Z REN, 100% +/- 1%; P <.05).']

['To evaluate the clinical factors predicting the significantly elevated high-sensitivity C-reactive protein (hs-CRP) concentrations, defined herein as hs-CRP > or = 3 mg/L, in adult males with untreated obstructive sleep apnea syndrome (OSAS).', 'Cross-sectional study.', 'Tertiary referral center.', 'Sixty-five consecutive male patients with newly diagnosed OSAS were enrolled to receive complete medical history review, physical examination, in-laboratory overnight polysomnography, and hs-CRP test. The patients had no current or history of cardiovascular disease. The patients had a mean age of 38.2 +/- 9.9 years, body mass index (BMI) of 27.4 +/- 3.5 kg/m(2), and Epworth Sleepiness Scale (ESS) of 11.3 +/- 4.6. The serum levels of hs-CRP were assessed using peripheral venous blood samples.', 'Twenty-three percent of the overall patients had significantly elevated serum levels of hs-CRP. The increase of hs-CRP correlated fairly with BMI, apnea-hypopnea index (AHI), tonsil size, and ESS (r = 0.450, 0.398, 0.393, and 0.300, respectively; all P < or = 0.05) after adjustment for conventional coronary heart disease risk factors. However, only the AHI could predict for significantly elevated hs-CRP after stepwise multiple linear regression (R(2) = 0.251, P < 0.001).']

['To assess religious perceptions and activities of physicians and older patients and to determine whether religious activities are associated with life satisfaction.', 'A cross-sectional survey of practicing Virginia internists and psychiatrists and hospitalized or institutionalized (nursing home) older adults.', 'One hundred randomly sampled practicing physicians and 55 hospitalized or institutionalized older patients.', 'A mailed survey was used for the physicians and a structured interview for the patients. All subjects provided information pertaining to demographics and life satisfaction using the Life Satisfaction Index (LSI-B). For physicians or patients who engaged in any religious activity, the Intrinsic/Extrinsic Religiosity (I/E-R) scale was used.', 'Of the 100 physicians (49 internists and 51 psychiatrists) who answered the survey (50% response rate), 75% used religious activity as a coping resource (39% somewhat, 36% definitely). There was a positive correlation between intrinsic religious activity (e.g., prayer, Bible reading) and life satisfaction (r = .293, P = .042). Of the 55 patients interviewed, 47 (86%) used religion as a coping resource, and intrinsic religious activity was positively associated with life satisfaction (r = .843, P < .001). Even after controlling for age, gender, health, and marital status, intrinsic religious activity remained a predictor of higher life satisfaction.']

['Radiotherapy for biochemical prostate cancer recurrence after prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods of identifying patients unlikely to benefit from salvage radiotherapy are needed. Altered expression of the adhesion molecule E-cadherin may be associated with the invasive and metastatic phenotype. We examined the relationship between E-cadherin expression and outcomes after salvage radiotherapy.', 'E-cadherin expression was examined by immunohistochemistical analysis of a tissue microarray of prostatectomy tissues from patients who underwent salvage radiotherapy. The relation between E-cadherin staining, other risk factors and biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier and Cox regression methods.', 'Of 37 analyzable cases 25 showed aberrant E-cadherin expression, while the remainder had normal expression. At a median clinical followup of 40 months univariate analysis demonstrated that E-cadherin staining was not associated with Gleason score, extracapsular extension, surgical margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen, complete biochemical response after radiotherapy or adjunctive hormonal therapy but it was associated with seminal vesicle invasion. Two-year failure-free survival was 55% in patients with aberrant E-cadherin expression compared with 92% in patients with normal E-cadherin expression (p = 0.02). Multivariate analysis confirmed that aberrant E-cadherin expression was associated with salvage radiotherapy failure (p = 0.03).']

['Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population.', "In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis."]

['To determine whether the "second gas effect" is valid, we determined the pharmacokinetics of 0.2% enflurane with or without 80% N2) (n = 7 each) under controlled constant volume ventilation in 14 young healthy male patients before their operations. The alveolar (end-tidal) concentration (FA) and inspired concentration (FI) at the mouthpiece and the arterial blood concentration of enflurane were measured, and the ratio of FA to FI was calculated. The FA/FI of enflurane increased rapidly during the first few minutes of administration and then increased slowly. No significant difference was found in the FA/FI between the two groups at any time point (P > 0.05). The arterial blood concentrations of enflurane increased progressively and were not significantly different between the two groups at any time point (P > 0.05). The results indicate that, at high concentrations, N2O neither facilitated the increase of FA nor enhanced the uptake of a companion gas. The second gas effect is a nonexistent phenomenon in clinical practice because the concentrating effect is very weak and the augmentation effect is nonexistent under controlled ventilation.']

['Pseudomonas aeruginosa is a leading cause of healthcare-associated infections in the intensive care unit (ICU).', 'To investigate an unexplained increase in the incidence of P.\xa0aeruginosa recovered from clinical samples in the ICU over a two-year period.', 'After unsuccessful epidemiological investigation by conventional tools, P.\xa0aeruginosa clinical isolates of all patients hospitalized between January 2010 and July 2012 were typed by a novel double-locus sequence typing (DLST) method and compared to environmental isolates recovered during the investigation period.', 'In total, 509 clinical isolates from 218 patients and 91 environmental isolates were typed. Thirty-five different genotypic clusters were found in 154 out of 218 patients (71%). The largest cluster, DLST 1-18, included 23 patients who were mostly hospitalized during overlapping periods in the burn unit. Genotype DLST 1-18 was also recovered from floor traps, shower trolleys and the shower mattress in the hydrotherapy rooms, suggesting environmental contamination of the burn unit as the source of the outbreak. After implementation of appropriate infection control measures, this genotype was recovered only once in a clinical sample from a burned patient and twice in the environment, but never thereafter during a 12-month follow-up period.']

["Mutations in the human FOXP2 gene cause speech and language impairments. The FOXP2 protein is a transcription factor that regulates the expression of many downstream genes, which may have important roles in nervous system development and function. An adequate amount of functional FOXP2 protein is thought to be critical for the proper development of the neural circuitry underlying speech and language. However, how FOXP2 gene expression is regulated is not clearly understood. The FOXP2 mRNA has an approximately 4-kb-long 3' untranslated region (3' UTR), twice as long as its protein coding region, indicating that FOXP2 can be regulated by microRNAs (miRNAs).", "We identified multiple miRNAs that regulate the expression of the human FOXP2 gene using sequence analysis and in vitro cell systems. Focusing on let-7a, miR-9, and miR-129-5p, three brain-enriched miRNAs, we show that these miRNAs regulate human FOXP2 expression in a dosage-dependent manner and target specific sequences in the FOXP2 3' UTR. We further show that these three miRNAs are expressed in the cerebellum of the human fetal brain, where FOXP2 is known to be expressed."]

['Several studies have shown the effect of dietary patterns on breast cancer risk, but none has been conducted in Argentina. The aim of this study was to extract dietary patterns from Food Frequency Questioner, to estimate their effect on breast cancer occurrence while taking into account aggregation factors (family history of breast cancer) and to explore the sensitivity of the estimates to changes in the assumptions.', 'A principal component exploratory factor analysis was applied to identify dietary patterns, which were then included as covariates in a multilevel logistic regression. Family history of BC was considered as a clustering variable. A multiple probabilistic sensitivity analysis was also performed.', 'The study included 100 cases and 294 controls. Four dietary patterns were identified. Traditional (fat meats, bakery products, and vegetable oil and mayonnaise) (OR III tertile vs I 3.13, 95% CI 2.58-3.78), Rural (processed meat) (OR III tertile vs I 2.02, 95% CI 1.21-3.37) and Starchy (refined grains) (OR III tertile vs I 1.82, 95 % CI 1.18-2.79) dietary patterns were positively associated with BC risk, whereas the Prudent pattern (fruit and non-starchy vegetables) (OR III tertile vs I 0.56, 95% CI 0.41-0.77) showed a protective effect. For Traditional pattern, the median bias-adjusted ORs (3.52) were higher than the conventional (2.76).']

['While evidence suggests that lobar intracerebral haemorrhage (ICH) is linked with dementia and cognitive impairment, the association between cognition and mortality risk from ICH is unclear.', 'To examine the association between dementia or cognitive impairment and short- and medium-term mortality post ICH.', "Patients with primary ICH were classified into lobar and non-lobar ICH using radiological criteria. Patients' characteristics and radiological measures were collected at the baseline along with history of dementia and cognitive impairment. Mortality risks at 7, 30, 60, and 90 days were assessed using multiple logistic regression adjusting for potential confounders identified as significant associates in univariate models.", 'A total of 136 patients (males 50%, mean age 77 years, SD 10) were included in this study. Out of 53 (39%) patients with lobar ICH 47 (89%) were classified as having possible and 6 (11%) as probable cerebral amyloid angiopathy (CAA). In lobar ICH the prevalence of history of dementia or cognitive impairment, confusion at presentation, previous ICH, multiple haemorrhages, and initial haematoma volume were significantly higher (p<0.05). In lobar ICH the significant mortality predictors (p<0.05) were history of dementia or cognitive impairment (90 days), prior antiplatelet use (60 and 90 days), initial haematoma volume (60 days), male sex (30 and 60 days), age (30, 60, 90 days), and low Glasgow Coma Scale (GCS) (7 and 30 days). In non-lobar ICH prior use of anticoagulation, initial haematoma volume, low GCS and age were significant mortality predictors (p<0.05).']

['Recent studies have demonstrated that mouthwash made with the traditional Japanese medicine hangeshashinto exhibits anti-inflammatory action and alleviates oral mucositis scores, including pain complaints, in patients undergoing chemoradiotherapy. However, no study has demonstrated the mechanism underlying how hangeshashinto provides pain relief in oral ulcers.', 'The analgesic effects on pain-related behaviors following the topical application of hangeshashinto were evaluated in an oral ulcer rat model treated with acetic acid using recently developed methods. Indomethacin, the representative anti-inflammatory agent, was intraperitoneally administered. The tissue permeability of the oral mucosa was histologically evaluated after applying the fluorescent substance FluoroGold.', 'The topical application of hangeshashinto in ulcerative oral mucosa suppressed mechanical pain hypersensitivity over 60 min, without any effects on healthy mucosa. The same drug application also inhibited oral ulcer-induced spontaneous pain. Indomethacin administration failed to block the mechanical pain hypersensitivity, though it did largely block spontaneous pain. Topical anesthesia with lidocaine showed hyposensitivity to mechanical stimulation in healthy mucosa. In the ulcer regions in which the oral epithelial barrier was destroyed, deep parenchyma was stained with FluoroGold, in contrast to healthy oral mucosa, in which staining was limiting to the superficial site.']

['To test the hypothesis that tissue factor release, thrombin activation, fibrin formation, and fibrinolysis after an isolated head injury are equal to those in patients without head injury, as well as to investigate the precise time course of the coagulation and fibrinolytic abnormalities after head injury, we performed prospective and retrospective studies.', 'In the prospective study, 5 patients with isolated head injury and 11 trauma patients without head injury took part in this study. Tissue factor antigen concentration, prothrombin fragment F1+2, thrombin antithrombin complex, fibrinopeptide A, and fibrin degradation products (D-dimer) were measured on the day of admission, and days 1, 2, 3, and 4 after admission. The levels of all five hemostatic molecular markers were markedly elevated on the day of admission, and then gradually decreased to day 4. The levels and the time course of these hemostatic markers in patients with isolated head injury were not different from those in the control patients. The same incidence of disseminated intravascular coagulation between the two groups was also observed. In the retrospective study, the records of fibrinopeptide Bbeta15-42, plasmin antiplasmin complex, plasminogen activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity in 76 trauma patients were reviewed. On the basis of the exclusion criteria, 9 patients with isolated head injury and 30 control patients were selected for the study group. Fibrinopeptide Bbeta15-42 and plasmin antiplasmin complex markedly elevated on the day of admission, then decreased on day 1, and tended to increase to day 5. Markedly elevated PAI-1 antigen and PAI-1 activity on the day of admission significantly decreased on day 1 and recovered to the normal values on day 5. The changes of these molecular markers in patients with isolated head injury were equal to those in the control patients.']

['As a common phytochemical, cyanidin 3-O-beta-glucoside (C3G) has a role in inhibiting inflammatory mediators; however, its mechanism of action remains unclear. The purpose of this study was to explore the effect of C3G on lipopolysaccharide (LPS)-stimulated TNFalpha and IL-6 expression in the human monocyte/macrophage cell line THP-1, and to explore the mechanisms involved.', 'Differentiated THP-1 cells were treated with different concentrations of C3G (0.005, 0.05, 0.5,10 microM) in the absence or presence of 1 ng/mL LPS. mRNA expression levels were detected by real time PCR, and secretion of TNFalpha and IL-6, phosphorylated IkappaBalpha, and nuclear factor-kappa B (NF-kappaB) P65 were monitored by ELISA or Western blotting analysis. The role of an inhibitor of IkappaBalpha phosphorylation, BAY 11-7082, in C3G inhibition of LPS-induced cytokines expression was investigated.', 'C3G (0.05-0.5 microM) treatment significantly inhibited LPS-stimulated TNFalpha and IL-6 mRNA expression and secretion of these proteins by THP-1 cells. Phosphorylation of IkappaBalpha and NF-kappaB nuclear translocation could be blocked by 0.5 microM C3G. BAY 11-7082 treatment abolished C3G-induced reduction of TNFalpha and IL-6.']

['A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line.', 'Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells.', 'After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate.']

['Although obesity has historically\xa0been described as a contraindication to UKA, improved outcomes with modern UKA implant designs have challenged this\xa0perception. The purpose of this study was to assess the influence of obesity on the outcomes of UKA with a robotic-assisted system at a minimum follow-up of 24\xa0months with the hypothesis that obesity has no effect on robotic-assisted UKA outcomes.', 'There were 746 medial robotic-assisted UKAs (672 patients) with a mean age of 64\xa0years (SD 11) and a mean follow-up time of 34.6\xa0months (SD 7.8). Mean overall body mass index (BMI) was 32.1\xa0kg/m', 'Patient BMI did not influence the rate of revision surgery to TKA (5.8\xa0%) or conversion from InLay to OnLay design (1.7\xa0%, n.s.). Mean postoperative Oxford knee score was 37 (SD 11) without correlation with BMI (n.s.). The type of prosthesis (InLay/OnLay) regardless of BMI had no influence on revision rate (n.s.). BMI did not influence 90-day readmissions (4.4\xa0%, n.s.), but showed significant correlation with higher opioid medication requirements and a higher number of physical therapy session needed to reach discharge goals (p\xa0=\xa00.031).']

['Alterations in specific signal transduction pathways may explain the hyperproliferation and abnormal differentiation of the keratinocytes as well as the increased expression of inflammatory cytokines seen in psoriasis. Major signalling pathways used by eukaryotic cells to transduce extracellular signals into cellular responses impinge on the mitogen-activated protein kinases (MAPKs).', 'To investigate the expression of the MAPK p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in psoriatic skin.', 'Keratome biopsies were taken from patients with plaque-type psoriasis. Western blot analysis was used to determine p38, ERK and JNK activity and protein levels, whereas kinase assays were used to examine the kinase activity of p38.', 'We demonstrated increased levels of the phosphorylated forms of p38 and ERK1/2 in lesional psoriatic skin compared with nonlesional psoriatic skin. No abnormality was found in the activation and expression of JNK1/2. Ex vivo kinase assays confirmed the increased activation of p38, and furthermore demonstrated increased kinase activity of the p38 isoforms p38alpha, p38beta and p38delta in lesional compared with nonlesional psoriatic skin. p38gamma was not detected in the psoriatic skin. Clearance of the psoriatic lesions, induced by climatotherapy at the Dead Sea for 4 weeks, led to a normalization in the activity of both p38 and ERK1/2.']

['To determine whether progestins counteract the cardioprotective effects of estrogen.', 'Controlled animal study.', 'Academic laboratory environment.', 'Female apolipoprotein E-deficient mice.', 'Mice were randomly assigned to groups receiving a sham operation plus placebo pellet, bilateral gonadectomy plus placebo pellet, or gonadectomy plus one of nine combinations of estrogen/progestin SC pellets.', 'Total plasma cholesterol, body weight, fat depot weight, uterine weight and size, and the cross-sectional area of fatty streaks in the aortic sinus were measured in each animal.', 'After 8 weeks of treatment, plasma cholesterol levels were significantly higher only in the ovariectomized and sham-operated animals that received placebo pellets. No differences in plasma cholesterol were observed relative to the type or amount of progestin administered. There was a reduction in fatty streaks in all of the hormone treatment groups as compared with both the ovariectomized and sham-operated animals that received placebo pellets.']

['Previous studies have suggested that reduced telomere length in circulating leucocytes in humans is associated with premature vascular disease and by implication, accelerated vascular ageing. Importantly, a link between telomere length in circulating leucocytes and the blood vessel wall has never been established. We, thus, investigated the relationship between vascular wall and circulating leucocyte telomere length in humans with and without overt vascular disease.', 'Aortic biopsies and paired blood leucocytes were obtained from 20 patients with asymptomatic abdominal aortic aneurysms (AAAs), undergoing elective open repair, and 12 morphologically normal aortas from a group of cadaveric organ donors of similar mean age. Telomere content was compared by quantitative PCR and expressed as telomere:genomic DNA ratio. The telomere:genomic DNA content was significantly reduced in wall biopsies of AAA vs. normal aorta, and this difference remained after adjusting for age and gender. There were strong correlations between leucocyte and vascular telomere content when the AAA and control groups were analysed either separately or grouped irrespective of the presence of vascular disease (r = 0.62, P < 0.001).']

['Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene.', "We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children.", "We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes.", 'Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses.']

['Seroconversion (SC) from hepatitis B envelope antigen (HBeAg) to anti-HBe usually indicates lower viral loads, resolved hepatitis activity and improved long-term outcomes. However, the role of viral factors in the development of SC remains largely unknown. We thus comprehensively studied these factors in 25 patients with sustained HBeAg SC and seven control patients with sustained loss of HBeAg.', 'We determined viral factors in serum samples obtained 1 year before, 6 months before, 3 months before, at the time of, 6 months after and 1 year after HBeAg SC or HBeAg loss. Precore A1896 and basal core promoter T1762/A1764 mutants were determined by polymerase chain reaction (PCR)-based assays. Serum HBV levels were determined by a real-time PCR assay.', 'We found that decline of serum viral load, frequently accompanied by hepatitis exacerbation, occurred within 1 year before HBeAg SC. The proportions of precore and BCP mutations also increased gradually throughout the process of HBeAg SC. The virologic features were similar between HBeAg SC group and HBeAg loss group. Before HBeAg SC or loss, genotype B patients had higher serum viral loads and lower proportions of BCP mutation compared with genotype C patients.']

['It is well-known that pulmonary function is altered in patients with ankylosing spondilitis (AS) owing mainly to the restriction of chest expansion. In addition to musculoskeletal factors, development of pulmonary function abnormalities may also deteriorate exercise tolerance of the patients.', 'The aim of this study was to examine the pulmonary function and exercise tolerance of AS patients.', 'A case controlled study.', 'Outpatient clinic of an university hospital.', 'Twenty-two men with the diagnosis of definite AS and 20 healthy controls matched according to age, sex, smoking habits and physical activity level were enrolled in this study. After a detailed physical examination, pulmonary function and exercise tolerance were assessed by "Sensormedics-Vmax 229" ergospirometry system. Maximal exercise testing was performed on a cycle ergometer using "10 watt ramp" protocol.', "Patients with AS had lower chest expansion, vital capacity and exercise tolerance than healthy subjects. Exercise tolerance strongly correlated with the patients' age, disease duration, chest expansion, modified Schober test, and vital capacity. In stepwise regression analysis, the best regression model for explaining the total variation of exercise tolerance selected only vital capacity as an independent variable (R²=54.9%)."]

['There is evidence that methamphetamine and sildenafil (Viagra) use are associated with sexual risk behaviour among men who have sex with men (MSM). We investigated the association of methamphetamine, sildenafil, and other substance use with unprotected receptive and insertive anal sex among MSM by conducting an encounter specific analysis.', 'Data were from a cross sectional, community based survey of MSM in San Francisco regarding behaviour during their most recent anal sex encounter. Mulitvariate regression analysed independent associations of specific substance use and demographic variables with unprotected anal sex behaviours.', 'The sample (n = 388) was diverse in race/ethnicity, age, income, education, HIV status, and homosexual/bisexual identification. More than half (53%) reported unprotected anal sex, including insertive (29%) and receptive (37%) during their most recent anal sex encounter; 12% reported unprotected insertive and 17% reported unprotected receptive anal sex with an HIV discordant or unknown partner. Methamphetamine was used by 15% and sildenafil was used by 6% of the men before or during the encounter; 2% used both drugs. In multivariate analysis controlling for demographic factors and other substance use, methamphetamine use was associated with unprotected receptive (odds ratio (OR), 2.03; 95% confidence interval (CI), 1.09 to 3.76) and sildenafil use was associated with unprotected insertive (OR, 6.51; CI, 2.46 to 17.24) anal sex. Effects were stronger with HIV discordant or unknown sex partners specifically.']

['To determine the influence of maternal chorioamnionitis and neonatal sepsis on interleukin-6 (IL-6) levels in cord blood and in blood obtained from very low birth weight (VLBW) infants within the first two hours of life.', 'Prospective clinical study.', 'Institute for the Care of Mother and Child, Prague.', 'We measured the serum levels of IL-6 in 30 consecutive VLBW infants born in our institute. IL-6 levels were evaluated in cord blood and in neonatal blood within 2 hours after delivery. Maternal chorioamnionitis and neonatal sepsis within the first 72 hours of life were monitored.', 'Maternal chorioamnionitis was detected in 7 of 30 patients (23.3%). There was no significant increase in IL-6 level in cord blood of newborns with maternal chorioamnionitis (p = 0.42). Serum level of IL-6 in this group did not differ from the level in newborns of mothers without signs of intraamniotic infection (p = 0.39). Neonatal early-onset sepsis was diagnosed in 7 of 30 patients (23.3%). There was no influence of neonatal sepsis on IL-6 level in cord blood (p = 0.98) and IL-6 level in neonatal blood (p = 0.19). We did not find any correlation between the group "chorioamnionitis positive" and "sepsis positive" (p = 0.31).']

['Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis.', 'We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena.', 'The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E.']

['Two putative methionine aminopeptidase genes, map (essential) and yflG (non-essential), were identified in the genome sequence of Bacillus subtilis. We investigated whether they can function as methionine aminopeptidases and further explored possible reasons for their essentiality or dispensability in B. subtilis.', 'In silico analysis of MAP evolution uncovered a coordinated pattern of MAP and deformylase that did not correlate with the pattern of 16S RNA evolution. Biochemical assays showed that both MAP (MAP_Bs) and YflG (YflG_Bs) from B. subtilis overproduced in Escherichia coli and obtained as pure proteins exhibited a methionine aminopeptidase activity in vitro. Compared with MAP_Bs, YflG_Bs was approximately two orders of magnitude more efficient when assayed on synthetic peptide substrates. Both map and yflG genes expressed in multi-copy plasmids could complement the function of a defective map gene in the chromosomes of both E. coli and B. subtilis. In contrast, lacZ gene transcriptional fusions showed that the promoter activity of map was 50 to 100-fold higher than that of yflG. Primer extension analysis detected the transcription start site of the yflG promoter. Further work identified that YvoA acted as a possible weak repressor of yflG expression in B. subtilis in vivo.']

['Heat stress, with the expression of heat stress proteins, has been shown to protect the rabbit heart in vitro against global ischaemia/reperfusion injury, though no benefit is apparent in an in vivo rabbit model of infarct size. The aim of this study was therefore to investigate this discrepancy and to discover whether heating itself has any effect which could negate the protection derived from myocardial stress protein synthesis.', '(1) To ascertain whether heat stress could limit infarct size in the absence of blood, isolated buffer perfused hearts, with or without prior heat stress, were subjected to 45 min of regional ischaemia and 120 min reperfusion, and the resulting infarct size was expressed as a percentage of the risk area (I/R%). (2) The observations were repeated in an isolated blood perfused heart model in which a support rabbit (heat stressed or control) was used to perfuse the isolated heart.', 'In the buffer perfused heart, prior heat stress reduced I/R from 70.8(SEM 4.4)%, n = 10, in controls to 51.5(5.7)%, n = 12 (p < 0.05). In hearts perfused by support rabbits, prior heat stress reduced I/R [from 34.7(3.7)%, n = 16, to 23.5(3.3)%, n = 15 (p < 0.05)] only when the perfusing rabbit was a control (not heat stressed). If the perfusing rabbit had been heated, I/R was greater in both heat stressed and control hearts [51.9(7.0)% and 44.9(3.3)%, p < 0.05 v control support rabbit].']

['To analyze a cohort of patients with HPV positive, oropharyngeal squamous cell carcinoma (OPSCC) treated with lower radiation dose to clinically involved lymph nodes.', 'We retrospectively identified patients with HPV positive, OPSCC treated with definitive chemoradiotherapy (70-74.4Gy) to the primary site and, since a post-radiation neck dissection was planned, 54Gy to the involved nodal areas. Neck dissection was ultimately omitted in all cases due to complete response. All patients were treated with a 3 field approach with sequential boost plans. Composite plans were generated retrospectively and primary tumor and lymph node GTVs were contoured and nodes were expanded by 5mm to form a CTV. Mean dose, dose to 95% (D95) and dose to 99% (D99) were determined.', 'Fifty patients treated from 2008 to 2010 with 113 involved nodes were identified. The median age was 57years, and 6%, 46%, and 48% were current, former, and never smokers. Ninety percent of patients received concurrent cisplatin based chemotherapy. Median D95 and D99 to involved nodes were 59.8Gy and 55.9Gy respectively. At a median follow up of 54.1months, two patients developed nodal failure and four developed metastatic disease. Five year loco-regional control, disease free survival and overall survival were 96%, 81% and 86% respectively.']

['We previously reported that paraoxonase-1 activity measurement may be useful for the evaluation of liver diseases. Because oxidative stress plays a role in liver apoptosis, and lipid peroxides are hydrolyzed by paraoxonase-1, we have extended our studies to explore the relationships between this enzyme and oxidative stress, fibrosis and apoptosis.', 'We measured paraoxonase-1 activity and concentration, soluble FAS concentration, serum fibrosis markers, and total peroxides in a group of patients with minimal hepatic changes (n=25), chronic hepatitis (n=51), or liver cirrhosis (n=17). We also measured the Knodell activity index in liver biopsies and performed FAS and PON1 immunostaining.', 'Patients with liver diseases showed an increase in soluble FAS, fibrosis markers and paraoxonase-1 concentrations, as well as a decrease in PON1 activity. Paroxonase-1 activity and concentration were correlated with soluble FAS (r=-0.43, P<0.001 and r=0.27, P=0.007, respectively). Paraoxonase-1 concentration showed a significant inverse association with FAS immunostaining (P=0.013) and a direct association with PON1 immunostaining (P<0.001).']

['Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system and has been associated with reduced perfusion in normal-appearing white matter (NAWM). The magnitude of this hypoperfusion is unclear. The present study aims to quantify NAWM perfusion with dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in patients with relapsing-remitting (RR) MS and in a control group.', 'The statistical power of a DCE-MRI acquisition to reveal hypoperfusion in MS was estimated using a Monte Carlo simulation: synthetic tissue curves with a contrast-to-noise ratio of 8 were generated for MS patients and control group using perfusion values reported in previous studies. A compartment-uptake model was fitted to these curves, yielding estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability-surface area product (PS). This was repeated 1000 times. Mean and standard deviation of the resulting distributions were used to calculate the statistical power of a DCE-MRI study to detect perfusion differences between 16 control subjects and 24 MS subjects.In an institutional review board-approved study, patients with RR-MS (n = 24; mean age, 36 years; 17 women, mean Enhanced Disability Status Scale score, 3.25) and patients without history or symptoms of neurological disorder (n = 16; mean age, 49 years; 9 women) underwent a DCE-MRI examination with a previously established MRI protocol (3D SPGR sequence; 2.1 seconds temporal resolution; 44 slices; spatial resolution, 1.7 × 1.7 × 3 mm). Regions were defined manually in the middle cerebral artery; in the frontal, periventricular, and occipital NAWM; in the pons; and in the thalamus, and CBF, CBV, and PS were quantified using a compartment-uptake model.Parameter differences between MS and control groups were evaluated using a mixed linear model with subjects as random effect and controlling for age and sex. A P value of less than 0.05 was considered to indicate statistical significance.', 'For all but one of previously reported effect sizes, the simulation study estimated a statistical power of 80% to 100% to detect reduced CBF in MS. In the patient study, mean (standard deviation) CBF in NAWM was 11.0 (15.1) and 10.4 (8.2) mL/100 mL per minute in the MS and control groups, respectively. Mean CBV in NAWM was 0.50 (0.45) mL/100 mL in the MS group and 0.48 (0.28) mL/100 mL in the control group. Mean values of PS in NAWM were 0.002 mL (0.027)/100 mL per minute in the control group and -0.001 (0.015) mL/100 mL per minute in the MS patients. Differences between patient groups were not statistically significant for CBF, CBV, mean transit time, and PS (P = 0.44, P = 0.20, P = 0.78, P = 0.66, respectively). In both groups, the influence of age on any parameter was nonsignificant. Cerebral blood flow and CBV in the thalamus and pons were significantly higher than in NAWM regions (P < 1e-4); mean transit time was significantly shorter than in NAWM (P < 1e-4). Permeability-surface area product was not significantly different from zero (P > 0.25) in all evaluated regions.']

['Furunculosis, a disease caused with gram negative bacteria Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination against furunculosis reduces mortality of Atlantic salmon but fails to eradicate infection. Factors that determine high individual variation of vaccination efficiency remain unknown. We used gene expression analyses to search for the correlates of vaccine protection against furunculosis in Atlantic salmon.', 'Naïve and vaccinated fish were challenged by co-habitance. Fish with symptoms of furunculosis at the onset of mass mortality (LR - low resistance) and survivors (HR - high resistance) were sampled. Hepatic gene expression was analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR. Comparison of LR and HR indicated changes associated with the protection and results obtained with naïve fish were used to find and filter the vaccine-independent responses. Genes involved in recruitment and migration of immune cells changed expression in both directions with greater magnitude in LR. Induction of the regulators of immune responses was either equal (NFkB) or greater (Jun) in LR. Expression levels of proteasome components and extracellular proteases were higher in LR while protease inhibitors were up-regulated in HR. Differences in chaperones and protein adaptors, scavengers of reactive oxygen species and genes for proteins of iron metabolism suggested cellular and oxidative stress in LR. Reduced levels of free iron and heme can be predicted in LR by gene expression profiles with no protection against pathogen. The level of complement regulation was greater in HR, which showed up-regulation of the components of membrane attack complex and the complement proteins that protect the host against the auto-immune damages. HR fish was also characterized with up-regulation of genes for proteins involved in the protection of extracellular matrix, lipid metabolism and clearance of endogenous and exogenous toxic compounds. A number of genes with marked expression difference between HR and LR can be considered as positive and negative correlates of vaccine protection against furunculosis.']

['Aldosterone secreting adenomas (aldosteronomas) have an unknown molecular origin. Ion channel currents are involved in signal transduction leading to aldosterone synthesis and secretion. HERG (human-ether-a-go-go-related gene) encodes for a potassium channel responsible for the outward rectifying delayed current and it is mutation prone. When mutated it causes most of the familial forms of both long QT and short QT syndromes. Abnormal repolarization in glomerulosa cells might increase aldosterone secretion or induce a proliferative advantage. The aims of this study were to: (1) evaluate HERG expression in aldosteronomas; (2) search for HERG somatic mutations; and (3) determine whether there is any relationship between the common HERG functional variant (A2690C, leading from lysine 897 to threonine, K897T) and aldosteronoma.', 'Aldosteronoma and blood samples from 17 patients were studied to evaluate HERG expression, full-length HERG complementary DNA sequencing, and genotyping for K897T alleles. The prevalence of HERG 897 alleles was also tested in a control population and a population consisting entirely of hypertensive individuals.', 'HERG was expressed in all aldosteronomas analysed. HERG somatic mutations were not detected. The 897T variant of HERG was significantly more common among patients with aldosteronoma (897T allele 41%) than in patients with moderate-severe essential hypertension (897T allele 20%, P = 0.007) or in the control population (897T allele 12%, P < 0.0001). The 897T/T genotype was present in 24% of the aldosteronoma patients versus 7% (P = 0.040) and 3% (P = 0.001) in essential hypertension and in the control population, respectively. When the chi test was performed considering the three groups together, the significance was similar (for alleles P < 0.0001 and for genotypes P = 0.004).']

['This study is to investigate the relationship between 25-Hydroxyvitamin D (25-OH-D) and pancreatic islet β cell function under different glucose tolerance statuses in China.', 'Totally, 180 patients with type 2 diabetes mellitus (DM group), 178 patients with impaired fasting glucose/impaired glucose tolerance (IFG/IGT group), and 160 normal control subjects (NGT group) were included to measure their body parameters and biochemical parameters. In oral glucose tolerance test, fasting serum 25-OH-D was assessed by the enzyme-linked immunosorbent assay (ELISA). Homeostasis model assessment for insulin resistance (Homa-IR), insulin acuity index (IAI), β-cell function index (Homa-BCF) as well as secretion index (IS) were determined.', 'The levels of 25-OH-D, IAI and Homa-BCF in the DM group and IFG/IGT group were significantly lower than that in NGT group (P < 0.05). Homa-IR in DM group and IFG/IGT group was significantly higher than that in the NGT group (P < 0.05). Pearson correlation analysis and partial correlation analysis showed that 25-OH-D was positively correlated with fasting insulin (FINS) and Homa-BCF (P < 0.05). Multiple stepwise regression analysis showed that 25-OH-D was one of the influential factors of pancreatic islet β cell function in patients with type 2 diabetes mellitus.']

['We previously demonstrated that short-term treatment with a standardized kudzu extract (NPI-031) reduced alcohol drinking by men and women in a natural setting. The present study was conducted in nontreatment-seeking heavy drinkers to assess the safety and efficacy of 4\xa0weeks of kudzu extract in an outpatient setting.', 'This randomized between-subject, double-blind, placebo-controlled study involved 2\xa0weeks of baseline, 4\xa0weeks of treatment, and 2\xa0weeks of follow-up. Seventeen men (21-33\xa0years) who reported drinking 27.6\u2009±\u20096.5 drinks/week with a diagnosis of alcohol abuse/dependence took either kudzu extract (250\xa0mg isoflavones, t.i.d.) or matched placebo on a daily basis. They reported alcohol consumption and desire to use alcohol using a wrist actigraphy device; twice weekly laboratory visits were scheduled to monitor medication adherence and adverse events.', 'Medication adherence was excellent and there were no adverse events and changes in vital signs, blood chemistry, and renal or liver function. There was no effect on alcohol craving, but kudzu extract significantly reduced the number of drinks consumed each week by 34-57\xa0%, reduced the number of heavy drinking days, and significantly increased the percent of days abstinent and the number of consecutive days of abstinence.']

['Administration of chemotherapy to premenopausal women shortens their reproductive lifespan by depleting nonrenewable oocytes. Preservation of fertility is a priority for many such women, and identification of women at risk of infertility is therefore important. However, age is the only patient characteristic currently recognized to be predictive of long-term ovarian function after chemotherapy.', 'Our objective was to assess markers of ovarian reserve and age as long-term predictors of ovarian function after chemotherapy.', 'We conducted a prospective, longitudinal study at a university hospital and research institute.', 'Patients included women who were premenopausal at the time of diagnosis of early breast cancer.', 'Ovarian function was assessed at 5 yr follow-up in relation to pretreatment hormonal and ultrasound markers of ovarian reserve.', 'Forty-two women received (neo-)adjuvant chemotherapy. Continuing menses 4-5 yr after diagnosis closely reflected ovarian activity as assessed by a range of serum markers, including estradiol, inhibin B, FSH, and anti-müllerian hormone (AMH). Pretreatment serum AMH, FSH, antral follicle count, and age predicted late ovarian activity by univariate analysis. However, only AMH was predictive in a multivariate logistic regression (odds ratio = 13.0; 95% confidence interval = 2.5-66.7); 0.71 ng/ml gave peak likelihood ratio of 7.0 with 54% sensitivity and 92% specificity. Bone mineral density fell over the 4-5 yr after diagnosis with greater loss in women with lower ovarian activity. Higher pretreatment AMH was associated with lower bone mineral density at both lumbar spine and hip at 5 yr (P < 0.02).']

['The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes.', "We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme's activity both in vitro and in vivo."]

['To examine the effect of antenatal indomethacin (AI) exposure on the incidence, response to postnatal indomethacin (PI), and need for surgical ligation of patent ductus arteriosus (PDA) in preterm infants.', "We performed a retrospective matched cohort study of infants born at < or = 30 weeks' gestation after exposure to AI administered because of preterm labour. Control subjects were infants unexposed to AI but with similar gestational age and birth weight. We compared the incidence of PDA, response to treatment with PI, and surgical PDA ligation rate between the two groups.", 'There was no difference in the incidence of PDA between AI infants (67.6%) and control subjects (66.6%). Only 22 of 54 (41%) infants in the AI group responded to PI therapy for symptomatic PDA closure, compared to 34 of 52 (65%) infants in the control group (P = 0.012). Thirty-two (59%) infants in the AI group required surgical PDA ligation after indomethacin therapy, compared with 18 infants in the control group (35%) (P = 0.01). Multivariate logistic regression analysis showed that AI exposure was independently associated with surgical ligation of PDA (adjusted odds ratio 3.07; 95% CI 1.46 to 6.45).']

['Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human brain disposition.', 'A mathematical model consisting of several physiological brain compartments in the rat was developed using rich concentration-time profiles from nine structurally diverse drugs in plasma, brain extracellular fluid, and two cerebrospinal fluid compartments. The effect of active drug transporters was also accounted for. Subsequently, the model was translated to predict human concentration-time profiles for acetaminophen and morphine, by scaling or replacing system- and drug-specific parameters in the model.', 'A common model structure was identified that adequately described the rat pharmacokinetic profiles for each of the nine drugs across brain compartments, with good precision of structural model parameters (relative standard error <37.5%). The model predicted the human concentration-time profiles in different brain compartments well (symmetric mean absolute percentage error <90%).']

['To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity.', 'A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization.', 'The study included 633\u2008200 children and 3\u2008209\u2008378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001).']

['Cholangiocarcinoma develops in 5% to 15% of patients with choledochal cysts, sclerosing cholangitis, and intrahepatic stones. The detection of cholangiocarcinoma in patients with premalignant biliary conditions has been difficult. Serum levels of carcinoembryonic antigen (CEA) have been neither sensitive nor specific for the diagnosis of cholangiocarcinoma. However, CEA has been shown to be present in cholangiocarcinomas by immunohistochemical staining. Therefore, we measured the level of CEA excreted in bile in patients with benign strictures, premalignant biliary diseases, and cholangiocarcinoma.', 'Bile was obtained from transhepatic stents in patients with benign biliary strictures (34), choledochal cysts (5), primary sclerosing cholangitis (6), intrahepatic cholelithiasis (5), and perihilar cholangiocarcinoma (25). Samples were analyzed for CEA using a solid phase, two-site immunoenzymetric assay.', 'Biliary CEA levels were significantly elevated (P < 0.01) in patients with cholangiocarcinoma (50.2 +/- 5.8 ng/mL) and intrahepatic cholelithiasis (57.4 +/- 10.4 ng/mL) compared with patients with benign strictures (10.1 +/- 3.9 ng/mL). Patients with sclerosing cholangitis (21.6 +/- 3.9 ng/mL) and choledochal cysts (20.0 +/- 16.5 ng/mL) had intermediate levels. In 5 patients undergoing resection of perihilar cholangiocarcinomas, the mean biliary CEA level decreased from a preoperative level of 46.8 +/- 6.7 ng/mL to a postoperative level of 11.3 +/- 5.6 ng/mL (P < 0.02). In 4 patients with progression of cholangiocarcinoma, biliary CEA increased from a mean of 53.3 +/- 6.9 ng/mL to 98.3 +/- 12.2 ng/mL (P < 0.02) over a mean interval of 9.5 months.']

['Although greater attention is currently being paid to participants in research, no studies have dealt so far with the issue of returning aggregate psychosocial results to cohort participants.', "(i) To explore participants' views about disclosure of the aggregate results of a French national psychosocial cohort survey on the epidemiology of preventive behaviour in women from families with a hereditary breast cancer risk. (ii) To assess whether it is worth consulting participants before designing the disclosure process.", 'A qualitative study using semi-structured face-to-face interviews and a thematic analysis based on Grounded Theory methods.', 'Nineteen interviews were conducted with cancer-free female BRCA mutation carriers/non-carriers aged 31-79 who had participated in a cohort survey by answering self-administered questionnaires.', "Participants showed considerable interest in the issue of result disclosure. The preferences expressed about disclosure were rarely relevant to the topic investigated, however, as they often focused on medical knowledge about BRCA and not on the psychosocial findings obtained. This confusion may have been due to the participants' experience of the survey procedures, including its longitudinal nature, the occurrence of very few interactions with the investigators and the wide range of topics addressed in the questionnaires."]

['Mucinous adenocarcinoma of the endometrium (MUC) is a rare histological variant of endometrial carcinoma accounting for 1-9% of endometrioid tumors. Few studies have characterized its clinical behavior. This is a case-control study at a single institution comparing the risk factors and clinical course of MUC relative to endometrioid adenocarcinoma.', "A case-control study was performed including patients treated for endometrial cancer between 1996 and 2006. 41 cases of mucinous adenocarcinoma were identified. Each case was matched with two controls of endometrioid histology by age and histological grade. Cases and controls were compared with regard to known risk factors for endometrial cancer and the extent of disease at diagnosis. Chi-square tests were used to compare proportions and Student's t-tests for the comparison of means. Multivariate regression was used to identify the independent predictors of lymph node metastases. Overall survival was calculated using the Kaplan-Meier method and compared with the Log-rank test. p<.05 was considered significant for all tests.", 'Cases and controls were matched by age and FIGO grade and were found to be similar in regard to ethnicity, body mass index and medical history. No significant difference in myometrial invasion (MI)>50% or the presence of lymph-vascular space invasion was found between cases and controls, however, 17% of patients with MUC had lymph node metastases compared to 3% of controls (p=.01). Multivariate analysis controlling for both tumor grade and depth of MI identified mucinous histology as an independent predictor of lymph node metastasis (p=.02). There was no difference in adjuvant treatment, recurrence rate or survival between the two groups.']

["Celastrol is a promising anti-tumor agent, yet it also elevates heat shock proteins (HSPs), especially HSP70, this effect believed to reduce its anti-tumor effects. Concurrent use of siRNA to increase celastrol's anti-tumor effects through HSP70 interference has been reported, but because siRNA technology is difficult to clinically apply, an alternative way to curb unwanted HSP70 elevation caused by celastrol treatment is worth exploring.", 'In this work, we explore three alternative strategies to control HSP70 elevation: (1) Searching for cancer cell types that show no HSP70 elevation in the presence of celastrol (thus recommending themselves as suitable targets); (2) Modifying HSP70-inducing chemical groups, i.e.: the carboxyl group in celastrol; and (3) Using signaling molecule inhibitors to specifically block HSP70 elevation while protecting and/or enhancing anti-tumor effects.', "The first strategy was unsuccessful since celastrol treatment increased HSP70 in all 7 of the cancer cell types tested, this result related to HSF1 activation. The ubiquity of HSF1 expression in different cancer cells might explain why celastrol has no cell-type limitation for HSP70 induction. The second strategy revealed that modification of celastrol's carboxyl group abolished its ability to elevate HSP70, but also abolished celastrol's tumor inhibition effects. In the third strategy, 11 inhibitors for 10 signaling proteins reportedly related to celastrol action were tested, and five of these could reduce celastrol-caused HSP70 elevation. Among these, the peptide deformylase (PDF) inhibitor, actinonin, could synergize celastrol's proliferation inhibition."]

['Self-rated health has been linked to important health and survival outcomes in individuals with co-morbid depression and cardiovascular disease (CVD). It is not clear how the timing of depression onset relative to CVD onset affects this relationship. We aimed to first identify the prevalence of major depressive disorder (MDD) preceding CVD and secondly determine whether sequence of disease onset is associated with mental and physical self-rated health.', 'This study utilised cross-sectional, population-based data from 224 respondents of the 2007 Australian National Survey of Mental Health and Wellbeing (NSMHWB). Participants were those diagnosed with MDD and reported ever having a heart/circulatory condition over their lifetime. Age of onset was reported for each condition. Logistic regression was used to explore differences in self-rated mental and physical health for those reporting pre-cardiac and post-cardiac depression.', 'The proportion of individuals in whom MDD preceded CVD was 80.36% (CI: 72.57-88.15). One-fifth (19.64%, CI: 11.85-27.42) reported MDD onset at the time of, or following, CVD. After controlling for covariates, the final model demonstrated that those reporting post-cardiac depression were significantly less likely to report poor self-rated mental health (OR:0.36, CI: 0.14-0.93) than those with pre-existing depression. No significant differences were found in self-rated physical health between groups (OR:0.90 CI: 0.38-2.14).']

['Computed tomography (CT) unenhanced attenuation value of <10 Hounsfield units (HU) has an excellent specificity (98%) to diagnose lipid-rich adrenocortical adenomas (ACAs) with a weaker sensitivity (71%).', 'To determine from a routine clinical perspective if unenhanced attenuation value is influenced by cortisol secretion in ACAs.', 'This was a retrospective study of cases collected between 2009 and 2012.', 'This study was conducted in a tertiary-care university hospital.', 'Seventy-two patients operated on for an ACA (Weiss score ≤ 2) were analysed. Thirty-four patients had an ACA oversecreting cortisol (Cush-ACA). Thirty-eight patients had an ACA without cortisol oversecretion (Non Hyper-ACA).', 'CT unenhanced attenuation value was correlated with the functional status. The Weiss score items were analysed.', 'Among the 34 patients with a Cush-ACA a minority (n = 7) had an unenhanced attenuation value under 10 HU. Among the high precontrast density (> 10 HU) Cush-ACAs, washout analysis after contrast administration was consistent with the benign nature of the tumor in ∼ 60% of the cases. Less than 25% clear cells (lipid-rich cells), a Weiss score item, was present in 50% of the Cush-ACAs in favour of a lipid-poor content.']

['Due to the paucity of data on urodynamics on the national level, we assessed the use of urodynamics in a large sample of individuals in the United States and identified predictors of increased complexity of urodynamic procedures.', 'Using administrative health care claims for adults enrolled in private insurance plans in the United States from 2002 to 2007, we identified those who underwent cystometrogram and abstracted relevant demographic and clinical data. We used logistic regression to identify predictors of higher urodynamic complexity over basic cystometrogram, specifically cystometrogram plus pressure flow study and videourodynamics.', 'We identified 16,574 urodynamic studies, of which 23% were cystometrograms, 71% were cystometrograms plus pressure flow studies and 6% were videourodynamics. Stress incontinence was the most common clinical condition for all studies (33.7%), cystometrogram (30.8%), cystometrogram plus pressure flow study (35.4%) and videourodynamics (24.4%). Urologists performed 59.8% of all urodynamics and gynecologists performed 35.5%. Providers with 14 or more urodynamic studies during the study period performed 75% of all urodynamics and were more likely to perform cystometrogram plus pressure flow study and videourodynamics. On regression analysis the most consistent predictors of cystometrogram plus pressure flow study and/or videourodynamics over cystometrogram were specialty (urologist) and the number of urodynamic tests performed by the provider.']

['To determine whether hypertonic stress promotes increases in inflammatory cytokine release through transient receptor potential vanilloid channel type 1 (TRPV1) signaling pathway activation in human corneal epithelial cells (HCECs).', 'Hyperosmotic medium was prepared by supplementing isotonic Ringers solution with sucrose. Ca2+ signaling was measured in fura2-AM-loaded HCECs using a single-cell fluorescence imaging system. Western blot analysis evaluated the phosphorylation status of EGFR, ERK, p38 MAPK, and nuclear factor (NF)-κB. ELISA assessed the effect of TRPV1 activation on the release of IL-6 and IL-8.', 'A 450 mOsm hypertonic stress elicited 2-fold Ca2+ transients that were suppressed by the TRPV1-selective antagonists capsazepine and JYL 1421. Such transients were enhanced by PGE2. Hypertonicity-induced EGF receptor (EGFR) transactivation was suppressed by preincubating HCECs with capsazepine, matrix metalloproteinase 1 (MMP1) inhibitor TIMP-1, broad-spectrum MMP inhibitor GM 6001, heparin-bound (HB)-EGF inhibitor CRM 197, or EGFR inhibitor AG 1478. ERK and p38 MAPK and NF-κB activation after EGFR transactivation occurred in tonicity and in a time-dependent manner. Hypertonicity-induced increases in IL-6 and IL-8 releases were suppressed by exposure to capsazepine, AG 1478, ERK inhibitor PD 98059, p38 inhibitor SB 203580, or NF-κB inhibitor PDTC.']

['This study was designed to evaluate functional outcome in patients treated with preoperative radiotherapy after low anterior resection and a coloanal anastomosis for low rectal cancer.', 'Functional outcome data from patients enrolled in a prospective randomized trial comparing 3 reconstructive procedures were evaluated with respect to administration of preoperative radiotherapy. Incontinence was assessed with a questionnaire on bowel function including the Fecal Incontinence Severity Index; sexual function was assessed with the Sexual Health Inventory for Men and a gender-specific questionnaire for women. Quality of life was assessed with SF-36 scores.', 'Of 364 patients enrolled, 153 (42%) had no radiotherapy or chemotherapy, and 211 (58%) had preoperative radiotherapy; 186 (51%) had chemotherapy in addition to radiotherapy. Comparison of irradiated vs. nonirradiated patients showed no significant differences in postoperative morbidity (29.9% vs. 35.3%; P = 0.27). Two-year follow-up of 297 patients showed greater impairment of bowel function in irradiated patients (n = 170) vs. nonirradiated patients (n = 127): e.g., mean number of daily bowel movements at 12 months, 4.2 +/- 3.5 vs. 3.5 +/- 2.6, P = 0.032; urgency, 85% vs. 67%, P = 0.002). Antidiarrheal use was significantly higher in irradiated patients vs. nonirradiated patients at 4 (P = 0.043), 12 (P = 0.002), and 24 (P = 0.001) months. Sexual Health Inventory for Men scores indicated poorer function in irradiated patients at 24 months (P = 0.039). Preoperative radiotherapy had no deleterious effects on quality of life. Multivariate analyses showed that negative effects of preoperative radiotherapy on urgency at 4 months (P = 0.002) and antidiarrheal use at 24 months were independent of reconstruction technique, but a positive effect of reconstruction with a J-pouch was still observed in patients who received radiotherapy.']

['This study evaluated the usefulness of 3-dimensional echocardiography (3-DE) for identifying permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead-related symptomatic tricuspid regurgitation (TR).', 'Eighty-seven patients underwent 3-DE examination: 50 patients with PPM, 17 with ICD, and 20 with cardiac resynchronization therapy devices. TR severity was classified as trivial/mild, moderate, or severe according to the ratio of TR area to right atrium area. The 3-DE identified the lead route and position at the tricuspid valve in 82 patients (94.2%). In 5 patients, images without lead-induced artifacts could not be obtained. TR severity was trivial/mild in 50 patients, moderate in 20 patients, and severe in 12 patients. In all patients with trivial/mild TR and all but 1 patient with moderate TR, leads were positioned on the annulus side between leaflets. Lead-induced obstruction to tricuspid valve closing was identified in 1 patient with moderate TR and in 7 of 12 patients with severe TR: 4 patients had septal leaflet obstruction, and 4 had posterior leaflet obstruction.']

['We have previously described that the sodium/lithium countertransport (SLC) in the erythrocyte cell membrane is closely linked to obesity and insulin resistance. Adiponectin and retinol-binding protein 4 (RBP-4) are believed to affect obesity and insulin resistance. In the present study, we aimed to further characterize the relationship between SLC, inflammatory markers, adiponectin and RBP-4.', 'We included 93 clinically healthy 58-year-old men selected to display variations in insulin sensitivity. High sensitivity C-reactive protein (hs-CRP), TNF-alpha, soluble TNF-alpha-receptors (sTNFR) 1 and 2, IL-6 and RBP-4 were measured using antibody-based techniques. Adiponectin was determined by a radioimmunoassay kit. The lithium concentration in the special flux medium was measured by atomic absorption spectrophotometry.', 'In univariate analyses, SLC correlated negatively with RBP-4 (r(s) = -0.256, p = -0.017) and to adiponectin (r(s) = -0.316, p = 0.003) and positively with TNF-alpha (r(s) = 0.346, p = 0.001) and hs-CRP (r(s) = 0.288, p = 0.005). There were no statistically significant correlations with sTNFR 1 or 2 or IL-6. SLC was negatively associated to body height (r(s) = -0.256, p = 0.013).']

['To determine the possibility of using the serum proinflammatory calcium-binding protein, or calgranulin C (S100A12), to assess activity and therapeutic efficiency in patients with periodic disease (PD) and other familial periodic fevers (FPFs).', 'Thirty-five patients with PD and other FPDs, which were verified by molecular genetic study, were examined. In accordance with the disease activity, the patients were divided into 2 groups. The investigators determined the concentration of S100A12 by solid-phase enzyme immunoassay and that of other acute-phase inflammatory markers (erythrocyte sedimentation rate (ERT), neutrophil counts, and fibrinogen and C-reactive protein (CRP) concentrations).', 'The serum concentration of S100A12 in the stage of disease activity was 466.7 (265.22--851.7) ng/ml, which was significantly higher than in remission (244.29 (118.93--409.85) ng/ml (p=0.000002). The highest S100A12 concentrations were noted in the patients with PD; these were 758.95 (434.80--1035.95) ng/ml; the S100A12 level in the majority of PD patients even during remission remained moderately higher. An investigation of the relationship of A100A12 to genetic variants found no differences between the patients homozygous for M694V and those with other genotypes (p=0.37). Estimation of the time course of therapy-induced changes in the serum S100A12 concentration revealed its considerable reduction (р=0.0018). However, normalization of S100A12 levels was not achieved in PD. The remaining increased S100A12 concentration in these patients may be suggestive of the activity of PD despite the absence of its clinical manifestations. S100A12 as a highly sensitive marker allows more exact evaluation of the anti-inflammatory effect of therapy. The S100A12 identification of the subclinical activity of autoinflammatory diseases made all the more important since traditional inflammatory markers, such as ERT, CRP, fibrinogen, and leukocyte counts, are less sensitive for these purposes. In our study, these markers were within the reference range in remission. No differences were found in the S100A12 levels between the groups with and without amyloidosis (p=0.62).']

['To determine whether perceptions of neighborhood safety and measures of neighborhood crime are independently associated within physical activity in youth.', "The study sample consisted of 14,125 youths in grades 6-10 (ages 11-15) who participated in the nationally representative cross-sectional 2009/10 Canadian Health Behaviour in School-Aged Children Survey. Participants responded to four questions about how safe their home neighborhood is and reported whether or not they accumulated at least 4h/week of physical activity in their free-time outside of school hours. Crimes against persons was assessed in 1 km radius buffers around participants' homes. Associations were assessed using logistic regression.", 'After controlling for crime and relevant confounders, the relative odds of being physically active outside of school was 0.52 (95% CI: 0.44-0.62) in youth whose perceptions of neighborhood safety were in the lowest quintile. After controlling for perceptions of safety and relevant confounders, the relative odds of being physically active outside of school was 0.75 (0.60-0.95) in youth from neighborhoods with crimes against persons scores in the highest quintile.']

['Inflammation has been associated with a wide range of chronic degenerative diseases, but the developmental factors contributing to the regulation of inflammation are poorly understood. This study investigates the within-individual association between antibody response to vaccination in adolescence and C-reactive protein (CRP) concentration in young adulthood.', 'In 1998-99, at age 14-15 years, a subset of participants (N = 96) in the Cebu Longitudinal Health and Nutrition Survey were administered a typhoid vaccine, and baseline and follow-up blood samples were drawn to assess the strength of the antibody response to vaccination. In 2005, at age 20-21 years, blood samples were drawn from the full cohort for measurement of CRP. N = 74 individuals had complete data at both time points. Bivariate associations and multivariate logistic regression models were evaluated to test the hypothesis that vaccine responsiveness in adolescence was significantly associated with CRP level in young adulthood.', 'There was a strong and statistically significant association between antibody response to vaccination in adolescence and CRP in young adulthood. Median CRP was more than four times higher among nonresponders than responders, and nonresponders were 2.3 to 3.6 times more likely to have CRP in the top tertile of the sample distribution.']

['Platelet hyperactivity is a contributing factor in the pathogenesis of cardiovascular disease and can be induced by elevated levels of circulating growth factors, such as insulin-like growth factor-1 (IGF-1). IGF-1 is a primer that cannot stimulate platelet activation by itself, but in combination with physiological stimuli can potentiate platelet functional responses via a phosphoinositide 3-kinase-dependent mechanism. In this study, we explored the role of the phosphoinositide 3-kinase p110α isoform in IGF-1-mediated enhancement of platelet function.', 'Using a platelet-specific p110α knockout murine model, we demonstrate that genetic deletion, similar to pharmacological inactivation of p110α, did not affect proteinase-activated receptor 4 signaling to Akt/protein kinase B but significantly reduced IGF-1-mediated Akt phosphorylation. The p110β inhibitor TGX-221 abolished IGF-1-induced Akt phosphorylation in p110α-deficient platelets, demonstrating that both p110α and p110β contribute to IGF-1-mediated Akt phosphorylation. Genetic deletion of p110α had no effect on IGF-1-mediated increases in thrombus formation on collagen and enhancement of proteinase-activated receptor 4-mediated integrin activation and α-granule secretion. In contrast, pharmacological inhibition of p110α blocked IGF-1-mediated potentiation of integrin activation and α-granule secretion. Functional enhancement by IGF-1 in p110α knockout samples was lost after TGX-221 treatment, suggesting that p110β drives priming in the absence of the p110α isoform.']

['To evaluate antileishmanial activity of crotamine, a toxin isolated from Crotalus durissus terrificus, in solution form and encapsulated in biodegradable microparticles in vitro.', 'Particles were analyzed on-chip by surface plasmon resonance and characterized by testing their diameters, zeta potential and encapsulation rate. The viability of promastigotes as well as murine macrophages was assessed. Furthermore, the phagocytic index was determined for macrophages, and cell supernatants were collected for the determination of TNF-α levels. An infection assay using Leishmania amazonensis-infected macrophages was also conducted.', 'The diameters and zeta potential of control particles (1.35 μm; -12.3 mV) and of those containing crotamine (3.09 μm; -20.9 mV) were adequate for the assays conducted. Crotamine-loaded particles were better captured by macrophages than control particles (increase of 12% in the phagocytic index), leading to increased TNF-α levels (196 pg/ml), and they also induced a significant decrease in the numbers of amastigotes compared to infected macrophages only.']

['To determine whether anterior shoulder instability is associated with an inherent deficiency of the bony glenoid concavity, which results in a reduced bony shoulder stability ratio (BSSR).', 'In this case-control study, we searched the institutional database for patients treated for unilateral recurrent anterior shoulder instability. We included 30 consecutive patients with atraumatic instability, 30 consecutive patients with traumatic instability, and 36 matched healthy controls, for a total of 96 shoulders. Computed tomography images of the unaffected shoulders of the instability patients were compared with images of the ipsilateral shoulders of age- and sex-matched healthy controls for differences in glenoid morphology. By use of a mathematical formula based on Pythagorean trigonometric identities, the mean BSSRs of the different groups were calculated and compared. Validation of the formula was accomplished by finite element analysis.', 'The mean BSSR of atraumatic instability patients was 17.9% ± 8.5% and therefore significantly lower\xa0than the mean BSSR of 31.1% ± 7.5% of the control group (13.2%; 95% confidence interval [CI], 9.1% to 17.4%; P < .001). The mean BSSR of the traumatic instability group was higher, at 23.9% ± 8.5% (P\xa0= .007), but still showed a deficit of 7.2% (95% CI, 2.8% to 11.7%; P\xa0= .002) compared with controls. The atraumatic instability group showed a mean reduction of 0.9 mm (95% CI, 0.6 to 1.1 mm; P < .001) in concavity depth and a decrease of 2.9° (95% CI, 0.4° to 5.3°; P\xa0= .021) in concavity retroversion, whereas the traumatic instability patients had a reduction of 0.4 mm (95% CI, 0.1 to 0.8 mm; P\xa0= .006) in concavity depth. Neither of the instability groups differed significantly from their respective controls in terms of glenoid concavity diameter, head radius, or glenoid vault morphology.']

['So-called 936-type phages are among the most frequently isolated phages in dairy facilities utilising Lactococcus lactis starter cultures. Despite extensive efforts to control phage proliferation and decades of research, these phages continue to negatively impact cheese production in terms of the final product quality and consequently, monetary return.', 'Whole genome sequencing and in silico analysis of three 936-type phage genomes identified several putative (orphan) methyltransferase (MTase)-encoding genes located within the packaging and replication regions of the genome. Utilising SMRT sequencing, methylome analysis was performed on all three phages, allowing the identification of adenine modifications consistent with N-6 methyladenine sequence methylation, which in some cases could be attributed to these phage-encoded MTases. Heterologous gene expression revealed that M.Phi145I/M.Phi93I and M.Phi93DAM, encoded by genes located within the packaging module, provide protection against the restriction enzymes HphI and DpnII, respectively, representing the first functional MTases identified in members of 936-type phages.']

['Increased expression of osteopontin (OPN), fibroblast growth factors (FGFs), and their type-1 receptor (FGFR-1) is associated with neointima formation and atherosclerosis. This study tested the hypothesis that ligand activation of FGFR-1 stimulates OPN expression in rat aortic smooth muscle cells (RASMCs), explored the signaling pathway involved, and assessed the functional consequences of activating this pathway on adventitial fibroblast (AF) migration in vitro.', 'Exogenous FGF-1 stimulated expression of OPN mRNA and protein in RASMCs in vitro in a dose- and time-dependent manner. OPN mRNA induction by FGF-1 was completely inhibited by either actinomycin D or cycloheximide, selective inhibitors of RNA polymerase and protein synthesis, respectively. OPN mRNA induction by FGF-1 was attenuated by PD 166866, a highly selective and potent FGFR-1 tyrosine kinase inhibitor. Addition of either PP2 or PD98059, specific inhibitors of Src and mitogen-activated extracellular signal-regulated kinase (MEK)/mitogen-activated protein (MAP) kinases, respectively, attenuated FGF-1-stimulated OPN mRNA expression. FGF-1 treatment of RASMCs enhanced RASMC-conditioned medium-stimulated AF migration; this effect was inhibited by pretreatment of RASMCs with either PD166866 or PP2. Immunodepletion of OPN from RASMC-conditioned medium inhibited both basal and FGF-1-stimulated AF migration.']

['To investigate the expression of nucleotide oligomerization domain 2 (NOD2) in the immortalized human corneal epithelial cell line (THCE), and its role in the innate immune response triggered by inactive Aspergillus fumigatus (Af) conidia.', 'The normal THCE cells were investigated as controls. After incubation with inactive Af conidia for 0.5, 2, 4, 6, and 8 hours, THCE cells were harvested, mRNA expression of NOD2 and receptor interacting protein 2 (RIP2) was detected by RT-PCR. Intracellular proteins including NOD2, NF-κB and proinflammatory cytokines such as TNF-α, IL-8, IL-6 in the cell supernatant were analyzed by ELISA.', 'Our data indicate that NOD2 expressed in the normal THCE cells. After triggered by the inactive Af conidia, the expression of NOD2, RIP2 mRNA and the secretion of NOD2, NF-κB, TNF-α, IL-8, IL-6 both increased in a time-depended manner, and reached the peak point at 4, 6, 6, 4, 6, 6, 4 hours, respectively. And after pretreated with NOD2 neutralizing antibody, the expression of RIP2, NF-κB, TNF-α, IL-8 both decreased dramatically at the peak point, while the secretion of IL-6 changed little.']

['Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of osteoarthritis (OA). Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury. Here, we investigated the intracellular signaling pathways involved in thrombin-induced HO-1 expression in human synovial fibroblasts (SFs).', 'Thrombin-mediated HO-1 expression was assessed with quantitative real-time (q)PCR. The mechanisms of action of thrombin in different signaling pathways were studied by using Western blotting. Knockdown of protease-activated receptor (PAR) proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of Nrf2 to the HO-1 promoter. Transient transfection was used to examine HO-1 activity.', 'Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of thrombin, and expression was higher than in normal SFs. OASFs stimulation with thrombin induced concentration- and time-dependent increases in HO-1 expression. Pharmacologic inhibitors or activators and genetic inhibition by siRNA of protease-activated receptors (PARs) revealed that the PAR1 and PAR3 receptors, but not the PAR4 receptor, are involved in thrombin-mediated upregulation of HO-1. Thrombin-mediated HO-1 expression was attenuated by thrombin inhibitor (PPACK), PKCδ inhibitor (rottlerin), or c-Src inhibitor (PP2). Stimulation of cells with thrombin increased PKCδ, c-Src, and Nrf2 activation.']

['Microdomain signalling mechanisms underlie key aspects of artery function and the modulation of intracellular calcium, with transient receptor potential (TRP) channels playing an integral role. This study determines the distribution and role of TRP canonical type 3 (C3) channels in the control of endothelium-derived hyperpolarization (EDH)-mediated vasodilator tone in rat mesenteric artery.', 'TRPC3 antibody specificity was verified using rat tissue, human embryonic kidney (HEK)-293 cells stably transfected with mouse TRPC3 cDNA, and TRPC3 knock-out (KO) mouse tissue using western blotting and confocal and ultrastructural immunohistochemistry. TRPC3-Pyr3 (ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate) specificity was verified using patch clamp of mouse mesenteric artery endothelial and TRPC3-transfected HEK cells, and TRPC3 KO and wild-type mouse aortic endothelial cell calcium imaging and mesenteric artery pressure myography. TRPC3 distribution, expression, and role in EDH-mediated function were examined in rat mesenteric artery using immunohistochemistry and western blotting, and pressure myography and endothelial cell membrane potential recordings. In rat mesenteric artery, TRPC3 was diffusely distributed in the endothelium, with approximately five-fold higher expression at potential myoendothelial microdomain contact sites, and immunoelectron microscopy confirmed TRPC3 at these sites. Western blotting and endothelial damage confirmed primary endothelial TRPC3 expression. In rat mesenteric artery endothelial cells, Pyr3 inhibited hyperpolarization generation, and with individual SK(Ca) (apamin) or IK(Ca) (TRAM-34) block, Pyr3 abolished the residual respective IK(Ca)- and SK(Ca)-dependent EDH-mediated vasodilation.']

['Cardiac arrest patients often suffer from dysfunction of multiple organ systems after return of spontaneous circulation (ROSC). The incidence of renal dysfunction in patients with out-of-hospital cardiac arrest (OHCA) is not well described. Renal dysfunction has been associated with worse outcomes in critical illness.', 'Renal dysfunction is common after OHCA, and renal dysfunction is independently associated with survival.', 'We performed a retrospective review of consecutive adult patients admitted to an intensive care unit after successful resuscitation from OHCA between 01/01/2005 and 12/31/2010. Patients were excluded for death or withdrawal of care within 24h, preexisting end-stage renal disease, or OHCA due to hyperkalemia. The RIFLE criteria were used to classify subjects with renal dysfunction into one of three categories - risk, injury, or failure - based on trending of serum creatinine concentration or glomerular filtration rate. Data were analyzed using descriptive statistics.', 'Of 364 patients, 38 were excluded due to death or withdrawal of care within 24h, 11 due to end-stage renal disease, and 4 due to OHCA from hyperkalemia, leaving 311 patients in the final analysis. The mean age was 58 (SD 16) years; 174 (59%) were male, VF/VT was the primary rhythm in 156 (50%), and 236 (80%) were comatose at hospital arrival. Among 311 patients, 32 (10.3%) developed acute renal failure (ARF), 27 (8.7%) developed acute kidney injury (AKI), and 56 (18.0%) developed risk of renal dysfunction. Of the 32 subjects that developed ARF, renal replacement therapy (RRT) was initiated on 13 (40.6%). Development of ARF was not associated with survival (OR 0.73; 95% CI 0.26, 2.05) after adjusting for initial rhythm or illness severity.']

['Total parenteral nutrition (TPN) alters gut cytokines and mucosal immunity and increases intercellular adhesion molecule-1 (ICAM-1) expression, gut neutrophil levels, and mortality after gut ischemia. Supplementation of TPN with glutamine partially supports mucosal immunity by preserving respiratory and intestinal IgA levels, maintaining the proper IgA-stimulating cytokine milieu within the intestine, and reducing intestinal ICAM-1 expression and neutrophil accumulation. This work investigates whether glutamine supplementation of TPN affects mortality in mice after gut ischemic insult.', 'Thirty-eight mice were randomized to receive chow, TPN, or 2% glutamine-supplemented TPN (GLN-TPN) for 5 days. After feeding their respective diets, gut ischemia/reperfusion (I/R) was induced with superior mesenteric artery occlusion for 30 minutes followed by resuscitation with 1 mL saline. Survival was recorded until 72 hours after reperfusion.', 'Survival time was significantly reduced in the TPN-fed mice compared with both chow-fed and GLN-TPN-fed mice (p < .05). Survival at 72 hours after reperfusion was also significantly lower in the TPN-fed mice than in the chow-fed and GLN-TPN-fed mice (p < .05)']

['Following damage to the intestinal epithelium, restoration of epithelial barrier integrity is triggered by a robust proliferative response. In other tissues, focal adhesion kinase (FAK) regulates many of the cellular processes that are critical for epithelial homeostasis and restitution, including cell migration, proliferation and survival. However, few studies to date have determined how FAK contributes to mucosal wound healing in vivo.', 'To examine the role of FAK in intestinal epithelial homeostasis and during injury, we generated intestinal epithelium (IE)-specific conditional FAK knockout mice. Colitis was induced with dextran-sulfate-sodium (DSS) and intestinal tissues were analyzed by immunohistochemistry and immunoblotting. While intestinal development occurred normally in mice lacking FAK, FAK-deficient animals were profoundly susceptible to colitis. The loss of epithelial FAK resulted in elevated p53 expression and an increased sensitivity to apoptosis, coincident with a failure to upregulate epithelial cell proliferation. FAK has been reported to function as a mechanosensor, inducing cyclin D1 expression and promoting cell cycle progression under conditions in which tissue/matrix stiffness is increased. Collagen deposition, a hallmark of inflammatory injury resulting in increased tissue rigidity, was observed in control and FAK knockout mice during colitis. Despite this fibrotic response, the colonic epithelium in FAK-deficient mice exhibited significantly reduced cyclin D1 expression, suggesting that proliferation is uncoupled from fibrosis in the absence of FAK. In support of this hypothesis, proliferation of Caco-2 cells increased proportionally with matrix stiffness in vitro only under conditions of normal FAK expression; FAK depleted cells exhibited reduced proliferation concomitant with attenuated cyclin D1 expression.']

['Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.', 'Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.', 'Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.']

["Our study's objective was to determine the relationship between state-specific maternal mortality ratios and the density of maternal-fetal medicine specialists.", 'State maternal mortality ratios from 1994 to 2001 were calculated from the Centers for Disease Control and Prevention WONDER database. Practitioner distribution data were obtained from professional associations. Demographic information regarding states was gathered from the 2000 US census data. Bivariable and multivariable analyses were conducted with the use of Spearman correlations and Poisson regression, respectively.', 'The median state maternal-mortality ratio was 7.5/100,000 live births. Our study showed that an increase of 5 maternal-fetal specialists per 10,000 live births results in a 27% reduction in the risk of maternal death (relative risk [RR] = 0.73, 95% CI = 0.58-0.93, P = 0.012). This risk reduction was based on a multivariable Poisson regression model that included the following variables and their significant interactions: state-specific percentages of mothers in poverty, mothers without a high school diploma, minority mothers, and teenage mothers.']

['Vitamin D deficiency is widespread and has been associated with many chronic diseases, including autoimmune disorders. A study was undertaken to explore the impact of low vitamin D levels on autoantibody production in healthy individuals, as well as B cell hyperactivity and interferon α (IFNα) activity in patients with systemic lupus erythematosus (SLE).', 'Serum samples from 32 European American female patients with SLE and 32 matched controls were tested for 25-hydroxyvitamin D (25(OH)D) levels, lupus-associated autoantibodies and serum IFNα activity. Isolated peripheral blood mononuclear cells were tested for intracellular phospho-ERK 1/2 as a measure of B cell activation status.', 'Vitamin D deficiency (25(OH)D <20 ng/ml) was significantly more frequent among patients with SLE (n=32, 69%) and antinuclear antibody (ANA)-positive controls (n=14, 71%) compared with ANA-negative controls (n=18, 22%) (OR 7.7, 95% CI 2.0 to 29.4, p=0.003 and OR 8.8, 95% CI 1.8 to 43.6, p=0.011, respectively). Patients with high B cell activation had lower mean (SD) 25(OH)D levels than patients with low B cell activation (17.2 (5.1) vs 24.2 (3.9) ng/ml; p=0.009). Patients with vitamin D deficiency also had higher mean (SD) serum IFNα activity than patients without vitamin D deficiency (3.5 (6.6) vs 0.3 (0.3); p=0.02).']

['This study was designed to explore the appropriate blood pressure (BP) target required to reduce cognitive decline and brain white matter lesions (WMLs) in elderly hypertensive patients.', 'Elderly patients (n = 294, ≥80 years of age) being treated for hypertension were enrolled in a longitudinal study examining cognitive impairment after an initial assessment and a period of 4 years. All patients underwent neurological and cognitive assessment, laboratory examination, and magnetic resonance imaging of the brain.', 'The 4-year follow-up examination revealed that body mass index, alcohol consumption, systolic blood pressure (SBP), diastolic blood pressure, and Mini-Mental State Examination (MMSE) all showed a significant decline, whereas fasting plasma glucose, white matter hyperintensities (WMH) volume, and the WMH/total intracranial volume (TIV) ratio were significantly increased when compared with baseline observations. Interestingly, the decline in MMSE, as well as the increment of WMH and WMH/TIV ratio was smaller in patients with SBP ranging from 140 to 160 mm Hg than in those whose SBP was lower than 140 mm Hg or higher than 160 mm Hg (P < .05). Furthermore, we observed that a 15 to 35 mm Hg targeted lowering of SBP in the elderly patients was more beneficial to our cognitive analysis than treatments that achieved less than 15 mm Hg or greater than 35 mm Hg (P < .05).']

['The benefits of cardiac resynchronization in inducing reverse ventricular remodeling in patients with left ventricular (LV) systolic dysfunction have been well established. Still, up to 30% of the patients fail to derive significant improvement from this therapy. A subset of "nonresponders" experience deterioration in LV function following cardiac resynchronization therapy (CRT). Characteristics of this patient population, however, have not been studied.', 'To determine characteristics of patients who experience deterioration in LV function following CRT.', "Clinical, electrocardiographic, and echocardiographic data were collected in 856 consecutive patients presenting for a new CRT device. For inclusion, all patients had an LV ejection fraction '40%, a QRS duration '120 ms, and available baseline and follow-up echocardiograms and electrocardiograms. Deterioration in LV function was defined as an absolute decrease of 5% or greater in ejection fraction from baseline. Multivariate models were constructed to identify variables significantly associated with deterioration.", 'A total of 507 patients met inclusion criteria, of which 60 (11.8%) met criteria for deterioration. Patients with deterioration were more likely to be men (86.7% vs 66.9%; P = .002), have a non-left bundle branch block morphology (41.7% vs 23.7%; P = .001), and a history of atrial fibrillation (66.7% vs 51.7%; P = .03). On comparing the pre-CRT QRS duration with the first biventricular-paced QRS duration post-CRT implant, it was found that patients with LV deterioration had significant QRS widening than did those without deterioration (ms) (+3.9 ± 34.1 vs -9.0 ± 27.4, P = .007, respectively). In multivariate analysis, QRS widening indexed to the baseline QRS duration was significantly associated with LV deterioration (odds ratio 1.14 [1.06-1.23]; P = .001).']

['To investigate the molecular epidemiological characteristics and antibiotic resistance profiles of Vibrio cholerae O139 in Shandong province.', 'A total of 13 strains of V. cholerae O139 (9 clinical strains and 4 environmental strains) isolated from cholera epidemics in Shandong province since 1997 were recovered and confirmed with serum agglutination and biochemical reaction. Pulsed-field gel electrophoresis (PFGE) was carried out for molecular subtyping. Virulence genes and drug resistance related genes were detected by PCR. Antibiotic susceptibility tests were performed using micro-broth dilution method.', 'Thirteen strains of V. cholerae O139 were differentiated into seven pulsetypes. One clinical strain and two environmental strains isolated from Jining in 2013 were clustered into the pulsetype namely KZGN11O139. CN0077, and an identical PFGE pattern of KZGN11O139. CN0002 was found among three clinical strains from Jinan in 2005, Jining in 2005 and Heze in 2009. Other pulsotypes were unique in China and found only in Shandong province. Because of deletion of ctxAB and tcpI, the PFGE patterns of two strains isolated from Yantai in 2000 and 2004 were different from other 11 strains which harbored ctxAB, tcpA, tcpI, rtxA, hlyA and toxR. All strains contained one or more drug resistance related genes such as intI 1, intI 4 and sxt, and were resistant to two kinds of antibiotics at least. Among the 12 kinds of antibiotics, the resistant ratioes to kamamycin, trimethoprim-sulfamethoxazole, ampicillin and gentamicin were 11/13, 9/13, 7/13 and 7/13, respectively.']

['To examine relationships among gastroesophageal reflux disease (GERD) symptoms, dietary behaviors, and sleep duration in the general population.', 'Cross-sectional.', 'Community-based.', 'There were 9,643 participants selected from the general population (54 ± 13 y).', 'None.', 'Sleep duration, sleep habits, and unfavorable dietary behaviors of each participant were assessed with a structured questionnaire. Participants were categorized into five groups according to their sleep duration: less than 5 h, 5 to less than 6 h, 6 to less than 7 h, 7 to less than 8 h, and 8 or more h per day. GERD was evaluated using the Frequency Scale for the Symptoms of GERD (FSSG) and participants having an FSSG score of 8 or more or those under treatment of GERD were defined as having GERD. Trend analysis showed that both the FSSG score and the number of unfavorable dietary habits increased with decreasing sleep duration. Further, multiple logistic regression analysis showed that both the presence of GERD (odds ratio = 1.19, 95% confidence interval (CI) = 1.07-1.32) and the number of unfavorable dietary behaviors (odds ratio = 1.19, 95% CI = 1.13-1.26) were independent and potent factors to identify participants with short sleep duration even after controlling for other confounding factors.']

['Collagen is a widely used naturally occurring biomaterial for scaffolding, whereas mesenchymal stem cells (MSCs) represent a promising cell source in tissue engineering and regenerative medicine. It is generally known that cells are able to remodel their environment by simultaneous degradation of the scaffolds and deposition of newly synthesized extracellular matrix. Nevertheless, the interactions between MSCs and collagen biomaterials are poorly known, and the strategies enhancing the extracellular matrix deposition are yet to be defined. In this study, we aim to investigate the fate of collagen when it is in contact with MSCs and hypothesize that protease inhibition will enhance their extracellular deposition of collagen fibrils.', 'Specifically, human MSCs (hMSCs) were exposed to fluorescence-labeled collagen with and without intracellular or extracellular protease inhibitors (or both) before tracing the collagen at both intracellular and extracellular spaces.', 'Collagen were internalized by hMSCs and degraded intracellularly in lysosomes. In the presence of protease inhibitors, both intracellular collagen fibril growth and extracellular deposition of collagen fibrils were enhanced. Moreover, protease inhibitors work synergistically with ascorbic acid, a well-known matrix deposition-enhancing reagent, in further enhancing collagen fibril deposition at the extracellular space.']

['Magnetic Resonance Imaging (MRI) allows a detailed "in vivo" macroscopic study of the human brain; previously, it has been demonstrated that Fluid Attenuated Inversion Recovery (FLAIR) sequence shows higher signal intensity of cortices belonging to limbic structures.', 'To measure and compare signal intensities (SI) of cytoarchitectonically different cortical regions.', 'In 22 adult subjects, without psychiatric or neurological diseases, FLAIR sequence was performed in coronal slices, perpendicular to the main hippocampal axis. Signal intensity was measured, with a region-of-interest (ROI) function, in 12 different cortical regions. We compared these values and grouped the cortices into five groups: (1) limbic cortices, (2) paralimbic agranular cortices, (3) paralimbic granular cortices, (4) parietal-type neopallium, (5) frontal-type neopallium. A t-test for comparison of paired samples was performed, considering p</=0.05 as statistically significant.', 'We found statistically significant differences amongst the different groups, with the exception of groups 1 and 2, which did not show differences between them. No statistically significant differences were found among cortices belonging to the same group.']

['The purpose of this study was to investigate the influence of core exercises on upper extremity function relative to skilled motor behavior and postural sway.', 'We examined the effects of core exercises on the skilled motor behavior and postural sway of 40 healthy students who were assigned randomly to the core exercise group or the control group. Independent variable is extent of exposure to core exercise and dependent variables are skilled motor behavior and postural sway. A Purdue pegboard which measures skilled motor behavior and a stabilometer which measures postural sway were used to evaluate the influence of core exercises. Pre-intervention and post-intervention skilled motor behavior and postural sway were compared between the core exercise group and control group using the Wilcoxon rank sum test; a significance level of α = 0.05 was considered statistically significant. Also, we investigated the application of core exercises in a clinical setting for one patient with cerebral vascular disease.', 'The post intervention skilled motor behavior (p = 0.04) and postural sway, LNG (p = 0.05), LNG/TIME (p = 0.04) and X LNG (p = 0.02) were significantly higher in the core exercise group than control group. In the case report, there were good results; function of the upper extremity improved after doing the exercises. There were positive changes in some daily living activities.']

['Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening.', 'Thirty-two male Sprague-Dawley rats aged 25.1± 2.4 weeks were randomly divided into three groups and received weekly intraperitoneal injections of normal saline (saline, n\u200a=\u200a7), or low (1.5 mg/kg to 1.75 mg/kg, n\u200a=\u200a14) or high (2.5 mg/kg, n\u200a=\u200a11) doses of DOX. The animals were treated for 2-12 weeks, and euthanized at pre-specified intervals (2, 4, 7, or 10+ weeks) to obtain histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness (medial thickness + adventitial thickness).', 'Lumen diameter was similar across all groups (saline: 315±34 µm, low DOX: 286±24 µm, high DOX: 242±27 µm; p\u200a=\u200a0.22). In comparison to animals receiving weekly saline, animals receiving weekly injections of 2.5 mg/kg of DOX experienced an increase in medial (23±2 µm vs. 13±3 µm; p\u200a=\u200a0.005), and total wall thickness (51±4 µm vs. 36±5 µm; p\u200a=\u200a0.022), respectively. These increases, as well as adventitial thickening became more prominent after normalizing for lumen diameter (p<0.05 to p<0.001) and after adjusting for age, weight, and total cumulative DOX dose (p\u200a=\u200a0.02 to p\u200a=\u200a0.01). Animals receiving low dose DOX trended toward increases in adventitial and total wall thickness after normalization to lumen diameter and accounting for age, weight, and total cumulative DOX dose (p\u200a=\u200a0.06 and 0.09, respectively).']

['This study examined whether depressed patients treated exclusively in primary care report less need for care and less acceptability of treatment options than those depressed patients treated in the specialty mental health setting after up to 6 months of treatment.', 'Cross-sectional study.', 'Forty-five community primary care practices.', 'A total of 881 persons with major depression who had received mental health services in the previous 6 months and who enrolled in 3 of the 4 Quality Improvement for Depression Collaboration Studies.', 'Patients were categorized into 1 of 2 groups: 1) having received mental health services exclusively from a primary care provider (45%), or 2) having received any services from a mental health specialist (55%) in the previous 6 months. Compared with patients who received care from mental health specialists, patients who received mental health services exclusively from primary care providers had 2.7-fold the odds (95% confidence interval [CI], 1.6 to 4.4) of reporting that no treatment was definitely acceptable and had 2.4-fold the odds (95% CI, 1.5 to 3.9) of reporting that evidence-based treatment options (antidepressant medication) were definitely not acceptable. These results were adjusted for demographic, social/behavioral, depression severity, and economic factors using multiple logistic regression analysis.']

['Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033).']

['Accumulating researches have shown that epithelial-mesenchymal transition (EMT) contributes to tumor metastasis. Leptin, a key adipokine secreted from adipocytes, shapes the tumor microenvironment, potentiates the migration of breast cancer cells and angiogenesis, and is also involved in EMT. However, the potential mechanism remains unknown. This study aims to explore the effect of leptin on EMT in breast cancer cells and the underlying mechanism.', 'With the assessment of EMT-associated marker expression in MCF-7, SK-BR-3, and MDA-MB-468 cells, the effect of leptin on breast cancer cells was analyzed. Besides, an array of pathway inhibitors as well as RNA interference targeting pyruvate kinase M2 (PKM2) were used to clarify the underlying mechanism of leptin-mediated EMT in vitro and in vivo.', 'The results demonstrated that leptin promoted breast cancer cells EMT, visibly activated the PI3K/AKT signaling pathway, and upregulated PKM2 expression. An antibody against the leptin receptor (anti-ObR) and the PI3K/AKT signaling pathway inhibitor LY294002 significantly abolished leptin-induced PKM2 expression and EMT-associated marker expression. SiRNA targeting PKM2 partially abolished leptin-induced migration, invasion, and EMT-associated marker expression. In vivo xenograft experiments indicated that RNA interference against PKM2 suppressed breast cancer growth and metastasis.']

['Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen [Radix Salviae miltiorrhizae (Labiatae)], showed renoprotective, neuroprotective and myocardial salvage effects. Previous studies demonstrated that MLB could effectively suppress the production of cytokines and their associated signaling pathways in activated human T cells.', 'The purpose of this study was to examine the beneficial effects of MLB on myocardial ischemia/reperfusion (MI/R) injury and to explore its potential mechanisms related to anti-inflammation.', 'Sprague-Dawley rats were grouped as sham group, model group and MLB-treated (15, 30 and 60\u2009mg/kg) groups. Animals were subjected to MI/R injury by the occlusion of left anterior descending artery for 30\u2009min followed by reperfusion for 3\u2009h. At the end of reperfusion, blood samples were collected to determine the serum levels of cardiac troponin (cTnI), creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6). Hearts were harvested to assess infarct size, histopathological changes and the activity of myeloperoxidase (MPO). The expression of phosphor-IkB-α and phosphor-nuclear factor kappa B (NF-κB) were assayed by western blot.', 'MLB administration significantly (p\u2009<\u20090.05) reduced: (1) ST-segment elevation (0.23\u2009mv), (2) the infarct size (22.5%), (3) histological scores of myocardial injury (1.67 score), (4) myocardial injury marker enzymes: cTnI (5.64\u2009ng/ml) and CK-MB (49.57\u2009ng/ml) levels, (5) pro-inflammatory cytokines: TNF-α (97.36\u2009pg/ml), IL-1β (93.35\u2009pg/ml) and IL-6 (96.84\u2009pg/ml) levels, (6) MPO activity (1.82\u2009U/mg), (7) phosphor-NF-κB (0.87) and phosphor-IkB-α (0.96) expression.']

['Diabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes and ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH).', 'db/db mice underwent 1.5 hours of hind limb ischemia followed by 1, 7, or 24 hours of reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24-hour period; the untreated group received Lactated Ringer (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity/intracellular localization, and poly-ADP-ribosylation of GAPDH.', 'PARP activity was significantly lower in the PJ34-treated groups than in the Lactated Ringer group at 7 and 24 hours of reperfusion. There was significantly less muscle fiber injury in the PJ34-treated group than in the Lactated Ringer-treated mice at 24 hours of reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7 hours and 24 hours of IR. There were significant increases in metabolic activity only at 24 hours of IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly-ADP-ribosylation, and nuclear translocation of GAPDH.']

['We sought to compare obstetric and perinatal outcomes of singletons born after extended embryo culture and a single blastocyst stage embryo vs a single cleavage stage embryo transfer.', 'This was a retrospective cohort study of 1543 fresh single embryo transfers using nondonor oocytes in women ≤40 years old from December 2008 through December 2012 at the reproductive unit of McGill University Health Center. The main outcome measures were perinatal outcomes including birthweight, low birthweight, small for gestational age, preterm delivery, preeclampsia, placental abruption, and neonatal complications. Covariates were maternal age, body mass index, smoking, cause of infertility, parity, and sex of the baby.', 'Transfers of 693 fresh single cleavage embryos and 850\xa0fresh single blastocysts resulting in 564 pregnancies and 381 singleton deliveries were analyzed. Blastocyst transfer resulted in a higher clinical pregnancy rate (50.1% and 19.9%) and live birth rate (33.5% and 13.8%) compared to cleavage embryo transfer, respectively (P < .001). Multivariate analyses for pregnancy revealed no increased risk of maternal or neonatal complications in pregnancies resulting from extended embryo culture.']

['In metastatic melanoma (MM) there is an agreement that a fast or slow progression should influence the choice between drugs with immediate impact (BRAF-inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for medical decision, although only estimated through surrogate markers (tumour load or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can be measured and 2- is a real prognostic factor.', 'Among all stage IV MM, we retrospectively select those with long follow-up who had two comparable total body computed tomography (CT) scans within the first 3 months, and did not receive meantime any treatment with a likely impact on MM kinetics. Kinetics index (KI) was calculated from changes in total metastatic volume (ΔTMV/ΔT).', 'In 126 patients, KI of progression ranges from 0 to 24,839 mm3/day. Overall survival (OS) was significantly much lower in the higher terciles of KI than in the lower ones (median OS of 459, 388 and 183 days, for KI of 0-99, 100-999 and > or =1000 mm3/day, respectively). In the multivariate analysis, KI was more predictive of OS than LDH or tumour load.']

['The role of positron emission tomography with the glucose analogue [18F] fluoro-2-deoxy-D-glucose (FDG-PET) in the initial staging of disease in patients with primary colorectal cancer (CRC) has not been adequately assessed.', 'To evaluate the additional value of FDG-PET as a staging modality, complementary to routine multidetector row computed tomography (MDCT) in patients with CRC.', 'Forty four patients with CRC underwent preoperative MDCT and FDG-PET. The accuracy of intraoperative macroscopic staging was also investigated compared with histopathological diagnosis. All FDG-PET images were evaluated with respect to detectability of the primary tumour, lymph node involvement, and distant metastases. Both MDCT and FDG-PET diagnoses and treatment plan were compared with surgical and histopathological results.', 'Thirty seven patients underwent surgery. Tumour detection rate was 95% (42/44) for MDCT, 100% (44/44) for FDG-PET, and 100% (37/37) for intraoperative macroscopic diagnosis. Pathological diagnosis of T factor was T1 in five, T2 in four, T3 in 24, and T4 in four cases. Concordance rate with pathological findings of T factor was 57% (21/37) for MDCT and 62% (23/37) for macroscopic diagnosis. Lymph node involvement was pathologically positive in 19 cases. Regarding N factor, overall accuracy was 62% (23/37) for MDCT, 59% (22/37) for FDG-PET, and 70% (26/37) for macroscopic diagnosis. For all 44 patients, FDG-PET findings resulted in treatment changes in only one (2%) patient.']

['Chronic infection with hepatitis B or C virus (HBV or HCV) is a leading cause of cirrhosis by unknown mechanisms of pathogenesis. Translocation of gut microbial products into the systemic circulation might increase because of increased intestinal permeability, bacterial overgrowth, or impaired clearance of microbial products by Kupffer cells. We investigated whether the extent and progression of liver disease in patients with chronic HBV or HCV infection are associated with microbial translocation and subsequent activation of monocytes.', 'In a retrospective study, we analyzed data from 16 patients with minimal fibrosis, 68 with cirrhosis, and 67 uninfected volunteers. We analyzed plasma levels of soluble CD14 (sCD14), intestinal fatty acid binding protein, and interleukin-6 by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) by the limulus amebocyte lysate assay, at presentation and after antiviral treatment.', 'Compared with uninfected individuals, HCV- and HBV-infected individuals had higher plasma levels of LPS, intestinal fatty acid binding protein (indicating enterocyte death), sCD14 (produced upon LPS activation of monocytes), and interleukin-6. Portal hypertension, indicated by low platelet counts, was associated with enterocyte death (P=.045 at presentation, P<.0001 after therapy). Levels of sCD14 correlated with markers of hepatic inflammation (P=.02 for aspartate aminotransferase, P=.002 for ferritin) and fibrosis (P<.0001 for γ-glutamyl transpeptidase, P=.01 for alkaline phosphatase, P<.0001 for α-fetoprotein). Compared to subjects with minimal fibrosis, subjects with severe fibrosis at presentation had higher plasma levels of sCD14 (P=.01) and more hepatic CD14+ cells (P=.0002); each increased risk for disease progression (P=.0009 and P=.005, respectively).']

['Schizophrenia is associated with poor theory of mind (ToM), particularly in the attribution of intentions to others. It is also associated with abnormal gaze behaviours and contextual processing. This study investigated to what extent impaired ToM in patients with schizophrenia is related to abnormal processing of social context.', 'We evaluated ToM using a nonverbal intention attribution task based on comic strips depicting social/nonsocial and contextual/noncontextual events while eye movements were recorded. Eye-tracking was used to assess processing time dedicated to visual cues contained in regions of interest identified in a pilot study. We measured cognitive contextual control on a separate task.', "We tested 29 patients with schizophrenia and 29 controls. Compared with controls, patients were slower in intention attribution but not in physical reasoning. They looked longer than controls at contextual cues displayed in the first 2 context pictures of the comic strips, and this difference was greater for intention attribution than for physical reasoning. We found no group difference in time spent looking at noncontextual cues. Patients' impairment in contextual control did not explain their increased reaction time and gaze duration on contextual cues during intention attribution."]

['The human equivalent of mouse mammary tumour virus (MMTV-LV) may have a role in the pathogenesis of primary biliary cirrhosis (PBC) and breast carcinogenesis. We investigated MMTV-LV prevalence in patients with liver disease of diverse aetiology and associations with hepatic expression of hormonal receptors, p53 protein and complicating hepatocarcinogenesis.', 'Nested PCR for MMTV-LV envelope was performed using tissue from 210 patients with liver disease and 20 patients with histologically normal liver. Hepatic expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PgR) and p53 protein was determined by immunohistochemistry. MMTV-LV expression was also determined in hepatocellular carcinoma (HCC) tissue from 21 patients, in 11 of whom paired non-tumourous liver tissue was available for comparison.', 'MMTV-LV envelope sequences were present in 25% (53/210) of liver disease biopsies but not in histologically normal liver (0/20) (P=0.02). There was no association between MMTV-LV presence and hepatic expression of ER-alpha or p53 protein. No liver sections were PgR positive. MMTV-LV prevalence was not significantly different in HCC tissue, paired non-tumourous chronic liver disease tissue from the same patients and liver disease tissue from patients without complicating HCC.']