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['The aim of this study was to examine the methylation status of intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and to elucidate the possible relationship between the cccDNA methylation and viral replicative activity in patients with HBV-related liver cirrhosis (HBV-LC).', 'The methylation status of HBV cccDNA was investigated by bisulfite sequencing in nonneoplastic tissues from 12 patients with HBV-LC who underwent surgical resection for combined hepatocellular carcinoma. Clinical, biochemical and virologic factors were evaluated with respect to the degrees of cccDNA methylation. We also examined the effect of methylation of cccDNA on viral transcription by an in vitro transcription assay.', 'Variable degrees of CpG methylation were present in the HBV cccDNA from patients with HBV-LC. Old age, low serum HBV DNA levels and low virion productivity were significantly associated with elevated cccDNA methylation. Virion productivity of cccDNA was also lower in HepAD38 cells with a higher degree of cccDNA methylation. In vitro transcription assays showed that the transcriptional activity of HBV cccDNA was suppressed by increased methylation of cccDNA.']

['We conducted a prospective study of 103 consecutive patients with non-small cell lung cancer who underwent a curative lobectomy to test whether circulating tumor cells detected in the peripheral blood by means of reverse transcriptase-polymerase chain reaction of carcinoembryonic antigen messenger RNA is a prognostic indicator independent of tumor stage in patients with non-small cell lung cancer.', 'We assayed for carcinoembryonic antigen messenger RNA by means of reverse transcriptase-polymerase chain reaction in peripheral blood taken at the time of diagnosis before an operation and again 2 to 3 weeks after an operation from patients with non-small cell lung cancer who underwent a curative lobectomy between March 1996 and April 1998. We analyzed the prognostic value of carcinoembryonic antigen messenger RNA expression in the patients with non-small cell lung cancer in a univariate and multivariate manner.', 'Patients with carcinoembryonic antigen messenger RNA in the preoperative blood samples had a poor survival when compared with those without carcinoembryonic antigen messenger RNA. Of these patients, the worst survival was seen in those with carcinoembryonic antigen messenger RNA in the postoperative blood samples. The multivariate stepwise analysis selected the preoperative carcinoembryonic antigen messenger RNA expression (P =.0004; relative risk, 0.21) and the pathologic stage of disease (P =.0002; relative risk, 1.43) as the independent prognostic factors for survival.']

['Few studies have examined the association of common genetic variants related to vitamin D metabolism and signaling to esophageal squamous cell carcinoma (ESCC).', 'We evaluated the association between 12 single nucleotide polymorphisms (SNPs) in four genes related to vitamin D levels and ESCC risk using data from a genome-wide association study. Participants were recruited from the Shanxi Upper Gastrointestinal Cancer Genetics Project and the Linxian Nutrition Intervention Trials, and included 1942 ESCC cases and 2111 controls. We used logistic models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the SNP associations, after controlling for age and gender.', 'None of the 12 evaluated SNPs in the four vitamin D-related genes were significantly associated with risk of ESCC. The strongest associations were for rs3794060 (P=0.07) and rs12800438 (P=0.08) in the DHCR7/NADSYN1 gene. No association between vitamin D-related SNPs and risk of ESCC was observed in a genotype score analysis that included all 12 SNPs. ORs for quartiles 2, 3 and 4 of the genotype scores were 0.83 (95% CI: 0.68, 1.01), 1.02 (0.85, 1.21), and 1.08 (0.89, 1.30), respectively, with no evidence for a significant monotonic trend (P=0.120).']

['In the seventh edition of TNM Classification of Malignant Tumours (TNM) staging, the stage-IIB category for lung cancer is comprised of four factors: lymph-node metastasis, chest-wall invasion, large tumor size (> 7 cm), and same-lobe nodules. Tumors are further classified into eight sub-categories based on each TN factor or factor combinations. This study evaluated the prognostic value of each TN factor or combinations for resected stage-IIB non-small-cell lung cancer (NSCLC).', 'We retrospectively studied 186 consecutive patients who had resections for NSCLC at Chiba University Hospital and were diagnosed as stage IIB according to the seventh edition of TNM staging.', 'Five-year survivals for each stage IIB were: T2bN1M0 = 47 ± 12% (± standard error); T3 (chest-wall invasion; N0M0) = 59 ± 7%; T3 (large tumor> 7 cm)=72 ± 11%; T3 (same-lobe nodules) = 78 ± 5%; T3 (invasion + > 7 cm)=44 ± 16%; T3 (invasion+same-lobe nodules) = 25 ± 22%; T3 (>7cm+same-lobe nodules) = 0%; and T3 (invasion + > 7 cm +same-lobe nodules)=0%. Among the four single factors, same-lobe nodules had the best prognoses, whereas T2bN1M0 had the worst prognoses. Comparing cases with single factors and multiple factors that decided stage IIB, cases with multiple factors had poorer prognoses (P=0.02).']

['Lymphoid enhancer-binding factor-1 (LEF1) is a target gene and central mediator of the Wnt signaling pathway. High LEF1 expression has been reported as a prognostic marker in several types of hematologic malignancies of adult patients.', "In this study, LEF1 expression was analyzed by real-time polymerase chain reaction (PCR) in 122 children with newly diagnosed ALL treated on the China NPCAC97 protocols. Patients' samples were dichotomized at the median value of control group and divided into LEF1(low) and LEF1(high) groups.", 'The LEF1 mRNA levels in patients with ALL were significantly higher than those of normal controls, and the LEF1 levels were dramatically decreased following induction therapy. In addition, LEF1(high) patients had lower white blood cell (WBC) count at diagnosis and lower minimal residual disease (MRD) levels at the time of complete remission as compared to LEF1(low) patients. Finally, our studies showed that high LEF1 expression is associated with favorable CR rate and overall survival (OS) in childhood ALL (5-year OS: LEF1(high) 92% vs. LEF1(low) 73%, P = 0.009). High LEF1 level was associated with a favorable relapse-free survival in standard-risk patients and also related to a better OS within the subgroup of patients with BCR-ABL-negative ALL.']

['To assess in an animal model the effect of maternal dietary calcium intake during pregnancy on the blood pressure of offspring.', 'Randomised controlled trial.', 'Ninety-eight 20-week-old female Wistar-Kyoto rats, giving birth to a total of 119 pups that were included in the follow up study.', 'Rats were randomised to a calcium deficient diet, a diet with the recommended calcium levels, or a diet with calcium content much higher than the recommended levels. After one month on the experimental diet they were bred. After birth, systolic blood pressure in the offspring was measured monthly till 52 weeks of age.', 'Blood pressure of the offspring.', 'The difference in blood pressure of the offspring between the normal and low maternal calcium group increased 0.49 mmHg per month (95% CI 0.18 to 0.84), 0.38 (0.07 to 0.68) between the low and high calcium group, and 0.12 (-0.20 to 0.43) between the normal and high calcium group. At the end of the follow up (52 weeks of age) blood pressure of the offspring in the deficient calcium group was 12.1 mmHg (95% CI 8.8 to 15.4, P < 0.0001) higher than in the normal calcium group and 7.5 mmHg (95% CI 4.4 to 10.5, P < 0.001) higher than the high calcium group. Blood pressure of the offspring in the high calcium group was 4.3 mmHg (95% CI 1.0 to 7.5, P = 0.01) higher than in the normal calcium group. In a multiple regression model maternal calcium intake during pregnancy was the strongest predictor of blood pressure of the offspring during adulthood.']

['Aminobiphosphonates, such as zoledronic acid (ZA), exert potent indirect antitumor effects and are currently being tested against human solid tumors. The antitumor actions of aminobiphosphonates, including angiostasis, are relevant to the pathogenesis of malignant pleural effusion (MPE), but no study has addressed the efficacy of these compounds against malignant pleural disease.', 'Here we hypothesized that treatment of immunocompetent mice with ZA would halt tumor progression in a mouse model of adenocarcinoma-induced MPE.', 'To induce MPE in mice, Lewis lung carcinoma cells were delivered directly into the pleural space. Subsequently, animals were treated with ZA in both a prevention and a regression protocol.', 'ZA treatment resulted in significant reductions in pleural fluid accumulation and tumor dissemination, while it significantly prolonged survival. These effects of ZA were linked to enhanced apoptosis of pleural tumor cells, decreased formation of new vessels in pleural tumors, and reduced pleural vascular permeability. In addition, ZA was able to inhibit the recruitment of mononuclear cells to pleural tumors, with concomitant reductions in matrix metalloproteinase-9 release into the pleural space. Finally, ZA limited the expression of proinflammatory and angiogenic mediators, as well as the activity of small GTP proteins Ras and RhoA, in tumor cells in vivo and in vitro.']

['To investigate the role of matrix metalloproteinase-9 (MMP-9) in the pre-ovulatory follicular fluid and culture media during in vitro fertilisation (IVF) cycle and to develop the zymographic pre-diagnosis marker for successful implantation and pregnancy in human IVF.', 'Controlled clinical study.', "IVF Laboratory, Women's Hospital Infertility Clinic and Dongguk University, Korea.", 'Women undergoing in vitro fertilisation treatment.', 'Experiments were designed for controlled clinical study with women undergoing IVF treatment. MMP-9 expressions in follicular fluid and culture media samples that had been collected during transvaginal oocyte retrieval were measured using zymography. MMP-9 activities and expressions were strongly correlated to a higher rate of fertilisation and pregnancy.', 'Fertilisation rates and ultrasonic evidence of intrauterine pregnancy by four weeks after embryo transfer.', 'MMP-9 activity was significantly higher in the pregnant group than in the non-pregnant group (P < 0.01). In contrast, MMP-2 activity was present in the follicular fluid and culture media of all women, and no difference in its expressions was found between the pregnant and non-pregnant groups. No correlation was found between the MMP-9 expression in follicular fluid and culture media and the fertilisation rates.']

['The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death.', 'Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice.', 'Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS). Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects.']

['Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria.', 'In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins.', 'Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt).', 'KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate.']

['Surveillance colonoscopy frequently occurs prior to recommended intervals. Studies delineating the reasons why premature surveillance occurs are limited. We sought to define the frequency in which premature surveillance colonoscopy occurs in the setting of an inadequate bowel preparation or with a provided patient clinical indication versus when premature surveillance colonoscopy occurs without any provided discernible rationale in the setting of adequate bowel preparation.', 'A retrospective cross-sectional cohort study of 700 patients undergoing colonoscopy for an indication of "surveillance of polyps" from 2008 to 2014 at two tertiary-care referral centers was carried out. Patients were deemed either "adherent" or "premature" based on US Multi-Society Task Force guideline intervals for surveillance colonoscopy. A documented decision-making rationale for premature surveillance was determined through review of the electronic medical record with assessment of clinical notes and endoscopy order and report.', 'Premature surveillance occurred in 43.0\xa0% (n\xa0=\xa0301) of all surveillance colonoscopies performed. Among the premature cases, rationale was attributed to inadequate bowel preparation in 17.3\xa0% (n\xa0=\xa052) and due to a new clinical indication in 21.6\xa0% (n\xa0=\xa065). Most commonly, in 61.1\xa0% (n\xa0=\xa0184) of premature cases, no rationale was documented for the early colonoscopy.']

['Interstitial collagen, especially type I, is a major component of atherosclerotic plaques and the matrix metalloproteinases (MMP) 1, 8 and 13 can initiate collagen breakdown. MMP-8 degrades type I collagen preferentially and more potently than MMP-1 or MMP-13. Although MMP-8 was thought to be produced only by neutrophils, it was recently reported to also be produced by endothelial cells, smooth muscle cells and macrophages in plaques.', 'Plasma MMP-8 concentrations were measured in 250 patients undergoing coronary angiography for coronary artery disease (CAD: >50% stenosis), which was found in 181 patients, of whom 69 had 1-vessel, 66 had 2-vessel, and 46 had 3-vessel disease. Compared with 69 patients without CAD, the 181 with CAD had higher MMP-8 concentrations (3.5 vs 3.0 ng/ml, p < 0.001). There was a stepwise increase in MMP-8 concentration depending on the number of stenotic vessels: 3.2 in 1-vessel, 3.6 in 2-vessel, and 4.3 ng/ml in 3-vessel disease (p < 0.001). Multivariate analysis showed that MMP-8 concentration was independently associated with CAD. The odds ratio for CAD was 1.22 (95%confidence interval = 1.07-1.39) for a 1 ng/ml increase in MMP-8 concentration.']

['The present study examined associations between psychological reactivity and hormonal responses to a standardized laboratory stressor (Trier Social Stress Test, TSST) in postmenopausal women.', 'Postmenopausal women aged 50-74 years undertook anxiety and mood assessments prior to and following the TSST. Blood samples were drawn at multiple timepoints for assessment of cortisol, adrenocorticotrophic hormone (ACTH) and dehydroepiandrosterone (DHEA).', 'Forty postmenopausal women completed the assessments. As expected, significant increases in anxiety and negative affect and decreases in positive affect were observed after the TSST; however, the magnitude of change in anxiety and mood varied considerably across individuals. Analyses indicated that greater increases in anxiety and negative affect after the TSST were associated with higher levels of cortisol, ACTH and DHEA after controlling for race, age, body mass index and smoking status. Changes in positive affect were not associated with cortisol, ACTH or DHEA.']

['There exists a treatment challenge with periungual warts. Topical immunotherapy with diphenylcyclopropenone (DPCP) has recently been reported to be an effective treatment for recalcitrant warts, including periungual types.', 'We aimed to evaluate the effectiveness and preference of topical immunotherapy with DPCP in treating periungual warts.', 'Twenty-seven patients with periungual warts who were treated with DPCP immunotherapy (2007 through 2010; Dongguk University Ilsan Hospital, Goyang, Korea) were retrospectively recruited. Other treatment modalities were also used in some patients. Lesions were grouped into the types according to the following locations: proximal nail fold, lateral nail fold and hyponychium. Total and group clearance rates as well as treatment periods according to location and disease duration were evaluated. A patient questionnaire was performed to assess the satisfaction for the treatments in those who received multiple therapies.', 'Total success rates were 85% (by subjects) and 91% (by individual lesions). Success rate and treatment period for proximal nail fold type seemed more desirable than other locations. Success rate decreased and treatment period increased as disease duration increased. The questionnaire revealed a significantly higher satisfaction rate for DPCP immunotherapy than for cryotherapy and pulsed-dye laser.']

['Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated.', 'SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4+ T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array.', 'SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro-inflammatory cytokines.']

['Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection.', 'We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection.']

['Blood pressure (BP) is controlled by a variety of systems, the activities of which vary throughout the day. As drugs are developed that selectively block these systems, the fall in BP may not be consistent over 24 h.', 'A total of 24 patients (aged >65 years) with systolic BP (SBP; >150 mm Hg) that had not been treated entered a substudy of a larger study performed in 74 patients. In a double blind, crossover study with a balanced design, they received placebo, atenolol 50 mg, perindopril 8 mg, felodipine 10 mg, or hydrochlorothiazide 50 mg. The study periods were 2 months. Ambulatory BP monitoring was performed at the end of each period, and was divided into awake periods (9:00 AM to 10:00 PM), sleep periods (12:00 AM to 6:00 AM), and morning periods (6:00 AM to 9:00 AM). Medication was taken at 9:00 AM.', 'The four drug classes lowered 24-h mean SBP (P <.05), but the fall with atenolol was less than with the other drugs. The fall in awake BP with perindopril was less than with felodipine or hydrochlorothiazide. Atenolol caused no significant fall in sleep or morning SBP, and the falls with the other three drugs were significant and were greater than the fall with atenolol. The fall in sleep BP with perindopril was greater than with the other drug classes. The awake-sleep difference in SBP increased with perindopril, stayed the same with felodipine and hydrochlorothiazide, and was reduced by atenolol.']

['Isolated late asthmatic reactions can be provoked by intradermal challenge of allergen-derived T-cell peptide epitopes.', 'The purpose of this study was to determine whether the isolated LAR is associated with the local accumulation of inflammatory cells, the expression of T(H)2 cytokines, and the production of pharmacologic mediators.', 'A randomized, placebo-controlled, crossover study design was used. The investigation involved bronchial and skin biopsies and bronchoalveolar lavage (BAL) fluids from 8 cat-allergic subjects who developed significant late asthmatic reactions 6 hours after intradermal injection of Fel d 1 chain 1-derived peptides (FC1Ps).', 'Immunostaining of bronchial biopsy specimens showed no changes in the numbers of eosinophils, neutrophils, basophils, mast cells, CD3(+), CD4(+) or CD8(+) T cells, CD25(+) cells or macrophages, or cells mRNA(+) for IL-4, IL-5, or IL-13 when the FC1P day was compared with the diluent control day. There were also no significant differences in eosinophil numbers, either in BAL fluids or in peripheral blood after FC1P challenge. Furthermore, there were no significant alterations in the concentrations of histamine, histamine-releasing factors, or eicosanoids (LTC(4)/D(4)/E(4), PGD(2), PGE(2), TXB(2), PGF(2alpha)) in BAL fluids. FC1Ps induced a significant (P <.05) elevation in CD8(+) cells in the skin and an unexpected decrease in IL-5 in BAL fluids (P =.043).']

["Previous studies have demonstrated that endoplasmic reticulum (ER) stress is activated in Alzheimer's disease (AD) brains. ER stress-triggered unfolded protein response (UPR) leads to tau phosphorylation and neuronal death.", 'In this study, we tested the hypothesis that hypoxia-induced m-calpain activation is involved in ER stress-mediated AD pathogenesis.', 'We employed a hypoxic exposure in APP/PS1 transgenic mice and SH-SY5Y cells overexpressing human Swedish mutation APP (APPswe).', 'We observed that hypoxia impaired spatial learning and memory in the APP/PS1 mouse. In the transgenic mouse brain, hypoxia increased the UPR, upregulated apoptotic signaling, enhanced the activation of calpain and glycogen synthase kinase-3β (GSK3β), and increased tau hyperphosphorylation and β-amyloid deposition. In APPswe cells, m-calpain silencing reduced hypoxia-induced cellular dysfunction and resulted in suppression of GSK3β activation, ER stress and tau hyperphosphorylation reduction as well as caspase pathway suppression.']

['The role of sphingosine-1-phosphate (S1P) and its receptors in the pathogenesis of atherosclerosis has not been investigated.', 'We hypothesized that the S1P receptor 3 (S1P(3)) plays a causal role in the pathogenesis of atherosclerosis.', 'We examined atherosclerotic lesion development in mice deficient for S1P(3) and apolipoprotein (Apo)E. Although S1P(3) deficiency did not affect lesion size after 25 or 45 weeks of normal chow diet, it resulted in a dramatic reduction of the monocyte/macrophage content in lesions of S1P(3)(-/-)/ApoE(-/-) double knockout mice. To search for putative defects in monocyte/macrophage recruitment, we examined macrophage-driven inflammation during thioglycollate-induced peritonitis. Elicited peritoneal macrophages were reduced in S1P(3)-deficient mice and expressed lower levels of tumor necrosis factor-α and monocyte chemoattractant protein-1. Bone marrow-derived S1P(3)-deficient macrophages produced less MCP-1 in response to lipopolysaccharide stimulation. In vitro, S1P was chemotactic for wild-type but not S1P(3)-deficient peritoneal macrophages. In vivo, S1P concentration increased rapidly in the peritoneal cavity after initiation of peritonitis. Treatment with the S1P analog FTY720 attenuated macrophage recruitment to the peritoneum. Studies in bone marrow chimeras showed that S1P(3) in both hematopoietic and nonhematopoietic cells contributed to monocyte/macrophage accumulation in atherosclerotic lesions. Finally, S1P(3) deficiency increased the smooth muscle cell content of atherosclerotic lesions and enhanced neointima formation after carotid ligation arguing for an antiproliferative/antimigratory role of S1P(3) in the arterial injury response.']

['Genetic heterogeneity is common in many neurologic disorders. This is particularly true for the hereditary ataxias where at least 36 disease genes or loci have been described for spinocerebellar ataxia and over 100 genes for neurologic disorders that present primarily with ataxia. Traditional genetic testing of a large number of candidate genes delays diagnosis and is expensive. In contrast, recently developed genomic techniques, such as exome sequencing that targets only the coding portion of the genome, offer an alternative strategy to rapidly sequence all genes in a comprehensive manner. Here we describe the use of exome sequencing to investigate a large, 5-generational British kindred with an autosomal dominant, progressive cerebellar ataxia in which conventional genetic testing had not revealed a causal etiology.', 'Twenty family members were seen and examined; 2 affected individuals were clinically investigated in detail without a genetic or acquired cause being identified. Exome sequencing was performed in one patient where coverage was comprehensive across the known ataxia genes, excluding the known repeat loci which should be examined using conventional analysis.', 'A novel p.Arg26Gly change in the PRKCG gene, mutated in SCA14, was identified. This variant was confirmed using Sanger sequencing and showed segregation with disease in the entire family.']

['There is little research on large-scale complex health care simulations designed to facilitate student learning of non-technical skills in a team-working environment. We evaluated the acceptability and effectiveness of a novel natural disaster simulation that enabled medical students to demonstrate their achievement of the non-technical skills of collaboration, negotiation and communication.', 'In a mixed methods approach, survey data were available from 117 students and a thematic analysis undertaken of both student qualitative comments and tutor observer participation data.', 'Ninety three per cent of students found the activity engaging for their learning. Three themes emerged from the qualitative data: the impact of fidelity on student learning, reflexivity on the importance of non-technical skills in clinical care, and opportunities for collaborative teamwork. Physical fidelity was sufficient for good levels of student engagement, as was sociological fidelity. We demonstrated the effectiveness of the simulation in allowing students to reflect upon and evidence their acquisition of skills in collaboration, negotiation and communication, as well as situational awareness and attending to their emotions. Students readily identified emerging learning opportunities though critical reflection. The scenarios challenged students to work together collaboratively to solve clinical problems, using a range of resources including interacting with clinical experts.']

['To study the effect of Jingjielianqiao Decoction in promoting leg ulcer in rabbits.', 'Nine adult male New Zealand albino rabbits with chronic leg ulcers were randomized into 3 groups, namely group A treated with Jingjielianqiao Decoction, group B with Shengjiyuhong Decoction, and group C with normal saline. Gross observation of the wounds was carried out regularly for evaluating the changes in the ulcerous area, depth and wound surface excretion. After 3 weeks of treatment, the tissues on the edge of the ulcer were sampled and prepared for routine pathological examination, electron microscopy and immunohistochemistry for vascular endothelial growth factor (VEGF) and CD34. The number of blood vessels and their areas were also recorded.', 'The wounds showed no significant differences between the 3 groups by gross observation during the treatment, but after completion of the 3-week treatment, routine pathological examination and electron microscopy revealed significant differences between the groups. Immunohistochemistry for VEGF and CD34 yielded comparable results between groups A and B (positive control), but showed significant differences between group C and the other two groups (P<0.01).']

['To investigate the association of the three angiotensin converting enzyme (ACE) genotypes, DD, ID, and II, with the occurrence or absence of coronary atherosclerosis and with myocardial infarction and hypertension.', 'Cohort analysis study.', 'North-Italy reference centre.', '388 white Italian patients (281 males; mean age 60.7 (SD 12.5) years) with proven coronary atherosclerosis (n = 255) or with angiographically normal coronary arteries (n = 133). A further group of 290 healthy blood donors was tested for allele frequency comparison.', 'ACE/ID polymorphism was analysed with polymerase chain reaction on DNA from white blood cells.', 'Coronary atherosclerosis, myocardial infarction, hypertension.', 'The D and I allele frequencies were respectively 0.63 and 0.37 in the overall healthy blood donor group and 0.66 and 0.34 in the overall study group. In the latter, univariate analysis showed (1) that coronary atherosclerosis (255 patients) was associated with the deletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001, and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients) was associated with the DD genotype (OR DD/II = 2.56, P = 0.007), but not with the ID genotype (OR DD/II = 1.96, P = 0.056). Finally, hypertension proved to be unrelated with the ACE genotype. The distribution between the three genotypes of known risk factors for coronary artery disease was similar. Logistic regression modelling, performed to test the association of the selected risk factors simultaneously with coronary atherosclerosis and myocardial infarction, showed that the deletion allele (whether DD or ID) was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated with the risk of infarction (although to a lesser extent than with coronary atherosclerosis).']

['To analyze the profile features of soft tissues of beautiful young men and women with Han nationality by polar coordinates.', "Sixty-two beautiful college students (aged 18-23 years, average 20.1 years, 31 men, 31 women) were chosen according to inclusion criteria as study samples. The lateral cephalograms of the samples were taken in natural head position. The polar system was established with the Bolton (Bo) point as the pole, and the Bo-N line as the polar axis. The polar coordinates were measured of the mark points on the soft tissues of the samples' maxillofacial regions respectively. The measured data were statistically analyzed with SPSS 17.0 software package.", 'There were no significant differences among the polar angles of the marking points on the soft tissues (P>0.05), the results were not statistically significant; there were significant differences among the measured data of line distances (P<0.01); the ratios of the polar radius of each mark point and Bo-N were not significantly different (P>0.05); there were significant differences among the values of Bo-Pos/ Bo-Sn, Bo-LL/Bo-Pos between men and women, which was statistically significant (P<0.05).']

['The apoptotic speck-like protein containing a caspase recruitment domain (ASC) is the essential adaptor protein for caspase 1 mediated interleukin (IL)-1beta and IL-18 processing in inflammasomes. It bridges activated Nod like receptors (NLRs), which are a family of cytosolic pattern recognition receptors of the innate immune system, with caspase 1, resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence, macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1beta. Furthermore, we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response, which triggers IL-1beta processing and secretion. However, the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor.', 'To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors, IL-1beta processing and secretion was investigated by ELISA in inflammasome reconstitution assays, stable expression in THP-1 and J774A1 cells, and by restoring the lack of endogenous ASC in mouse RAW264.7 macrophages. In addition, the localization of ASC and ASC isoforms was determined by immunofluorescence staining.', 'The three novel ASC isoforms, ASC-b, ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor, with one of the isoforms even showing an inhibitory effect. Consistently, only the activating isoforms of ASC, ASC and ASC-b, co-localized with NLRP3 and caspase 1, while the inhibitory isoform ASC-c, co-localized only with caspase 1, but not with NLRP3. ASC-d did not co-localize with NLRP3 or with caspase 1 and consistently lacked the ability to function as an inflammasome adaptor and its precise function and relation to ASC will need further investigation.']

['Endothelial E-selectin has been shown to play a pivotal role in mediating cell-cell interactions between breast cancer cells and endothelial monolayers during tumor cell metastasis. However, the counterreceptor for E-selectin and its role in mediating breast cancer cell transendothelial migration remain unknown.', 'By assessing migration of various breast cancer cells across TNF-alpha pre-activated human umbilical vein endothelial cells (HUVECs), we found that breast cancer cells migrated across HUVEC monolayers differentially and that transmigration was E-selectin dependent. Cell surface labeling with the E-selectin extracellular domain/Fc chimera (exE-selectin/Fc) showed that the transmigration capacity of breast cancer cells was correlated to both the expression level and localization pattern of E-selectin binding protein(s) on the tumor cell surface. The exE-selectin/Fc strongly bound to metastatic MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells, but not non-metastatic MCF-7 and T47D cells. Binding of exE-selectin/Fc was abolished by removal of tumor cell surface sialyl lewis x (sLe(x)) moieties. Employing an exE-selectin/Fc affinity column, we further purified the counterreceptor of E-selectin from metastatic breast cancer cells. The N-terminal protein sequence and cDNA sequence identified this E-selectin ligand as a approximately 170 kD human CD44 variant 4 (CD44v4). Purified CD44v4 showed a high affinity for E-selectin via sLe(x) moieties and, as expected, MDA-MB-231 cell adhesion to and migration across HUVEC monolayers were significantly reduced by down-regulation of tumor cell CD44v4 via CD44v4-specific siRNA.']

['Hysterectomy, with or without oophorectomy, is associated with increased cardiovascular disease (CVD) risk due, in part, to an adverse CVD risk factor profile. Large artery stiffening, a biomarker of vascular aging, increases the risk for CVD. We determined whether hysterectomy with or without bilateral oophorectomy (BLO) is associated with arterial stiffening in healthy postmenopausal women.', 'We conducted a cross-sectional study including estrogen-deficient postmenopausal women who had a hysterectomy with ovarian preservation (n = 24; mean ± SE age, 59 ± 1 y) or with BLO (n = 21; 58 ± 2 y) and had no hysterectomy/no BLO (n = 58; 58 ± 1 y). Arterial stiffness (arterial compliance and β stiffness index) was measured by ultrasonography of the carotid artery.', 'Carotid artery compliance was lower in women with hysterectomy alone and in women with hysterectomy with BLO compared with women with no hysterectomy (0.66 ± 0.03 and 0.71 ± 0.06 vs 0.89 ± 0.03 mm/mm Hg × 10, respectively, both P < 0.05). There were no differences in traditional CVD risk factors (ie, adiposity, blood pressure and fasted lipids and lipoproteins, glucose, and insulin) between the groups. After adjustment for age, menopause duration, previous menopausal hormone therapy duration, parity, waist-to-hip ratio, systolic blood pressure, and sex hormone-binding globulin, hysterectomy status remained a significant predictor of arterial compliance.']

['The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. The presence of postmortem thrombi, however, is a concern for the development of primary graft dysfunction. In this isolated lung reperfusion study, we looked at the need and the best route of preharvest pulmonary flush.', 'Domestic pigs were sacrificed by ventricular fibrillation and divided in 3 groups (n = 6 per group). After 1 h of in situ warm ischemia, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted after an anterograde flush (AF) through the pulmonary artery. Finally, in group III, lungs were explanted after a retrograde flush (RF) via the left atrium. After 3 h of cold storage, the left lung was assessed for 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) was calculated after reperfusion.', 'Pulmonary vascular resistance (dynes x sec x cm(-5)) was 1145 +/- 56 (RF) versus 1560 +/- 123 (AF) and 1435 +/- 95 (NF) at 60 min of reperfusion (P < 0.05). Oxygenation and compliance were higher and plateau airway pressure was lower in RF versus AF and NF, although the difference did not reach statistical significance. No differences in W/D were observed between groups after reperfusion. Histological examination revealed fewer microthrombi in the left lung in RF compared with AF and NF.']

['Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results.', 'We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years).', 'The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self-assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05).']

['Several studies have shown higher early mortality for ST-segment elevation acute coronary syndrome (STEACS), but late mortality remains consistently higher for non-ST-segment elevation acute coronary syndrome (NSTEACS). We hypothesized that ST-segment category at acute presentation is associated with the time course of coronary artery disease progression (CP) of nonculprit lesions in patients with acute coronary syndrome (ACS).', 'A total of 226 patients (182 men, age 65\xa0±\xa010\xa0years) with STEACS (n\xa0=\xa095) or NSTEACS (n\xa0=\xa0131) who underwent percutaneous coronary intervention (PCI) during initial hospitalization were studied. All patients underwent serial coronary angiograms (CAGs) performed immediately before PCI and at 7\xa0±\xa03\xa0months and 60\xa0±\xa010\xa0months after presentation. CP was defined as an increase in stenosis severity >15% of a nonculprit lesion between 2 serial CAGs.', 'The rate of CP between the first and second CAGs did not differ by ST-segment category at acute presentation. Compared to STEACS, NSTEACS had a higher rate of CP between the second and final CAGs (27.4 vs. 42.7%, P\xa0=\xa00.018). Multivariate analysis showed that the independent predictors of CP between the second and final CAGs were NSTEACS (odds ratio 2.709, P\xa0=\xa00.003), estimated glomerular filtration rate <60\xa0ml/min/1.73\xa0m']

['Giant hiatus hernia (GHH) are difficult to manage effectively. This study reports a laparoscopic, prosthesis-free technique to repair of GHH.', "Retrospective analysis of a prospectively populated database of a single surgeon's experience of GHH (>30 % intrathoracic stomach) repair using a novel, uniform technique was performed. Routine postoperative endoscopy, quality of life (QOL), and Visick scoring was conducted.", 'Surgery was conducted in 100 patients (70F, 30 M). Mean (standard deviation [SD]) age was 69.1 (±11.4), median (interquartile range) ASA was 2 (range, 2-3), and mean (SD) body mass index (BMI) was 29.1 (±4.5). Mean follow-up was 574.1 (±240.5) days. One (1 %) patient was converted to an open procedure due to technical issues. Median stay was 2.5 days (range, 2-4). One postoperative death occurred secondary to respiratory sepsis. Eight (8 %) patients had perioperative complications: 4 major (PE, non-ST elevation MI, postoperative bleed managed conservatively, infected mediastinal fluid collection); and 4 minor (pneumothorax, asymptomatic troponin leak, subacute small bowel obstruction, and urinary retention). Ninety-nine (99 %) patients had objective screening for recurrence at 3-6 months. Two (2 %) patients have had symptomatic recurrence of their hiatus hernia; both involved a recurrent fundal herniation. Another seven (7 %) had small (<2 cm), asymptomatic recurrences diagnosed only on routine follow-up. Seven (7 %) patients have required reintervention for dysphagia with endoscopic dilatation conducted to good effect in all cases. Two (2 %) patients have required revisional surgery: one for a symptomatic recurrence at 3 months and a second for recurrent mediastinal collection. The Visick score fell from a mean (SD) of 3 (±1.1) to 1.7 (±0.8) postoperatively (p < 0.0001). The mean (SD) QOL preoperatively was 87.8 (±24) versus 109.1 (±22.3) postoperatively (p < 0.0001).']

['The slight increase in cardiac troponin in the blood of patients with heart failure (HF) suggests that myofibrils are degraded in the myocardium and released in the circulation, reflecting a continuous and progressive injury process in the contractile system.', 'To correlate the serum levels of cardiac troponin T (TnT) at the hospital admission of patients with decompensated HF and prognosis.', 'A total of 79 consecutive patients, hospitalized due to decompensated HF, with LVEF < 45%, were included in the study. Patients were followed for 8 months. We excluded patients using intravenous inotropic agents, as well as those with acute coronary syndrome, pulmonary thromboembolism, creatinine levels > 2.5 mg%, liver failure, or neuromuscular diseases.', 'High levels of TnTc (>0.02 ng/ml) were detected in 37 patients (46.84%). The global mortality was 35.4%. In the groups with high TnT and low TnT levels (<0.02 ng/ml) there were, respectively, 19 versus 9 deaths (RR=2.4; 95%CI 1.24-4.63; p=0.011), 5 versus 4 heart transplants (RR=1,42; 95%CI 0.41-4.89; p=0.73), 11 versus 7 patients needed IV inotropic agents (RR=1.78; 95%CI 0.77-4.12; p=0.26) and 14 versus 10 patients were re-hospitalized (RR=1.85; 95%CI 0.95-3.6; p=0.10). Mean troponin levels were significantly higher in those individuals who died (0.071+/-0,119 vs 0.032+/-0.046; p=0.004). At the multivariate analysis, the persistence of the third sound and the need for IV inotropic agents showed to be independent predictors of death; however, we observed a higher tendency towards mortality for patients presenting high TnT when compared to those with low troponin levels (HR=2.64; 95%CI 0.91-7.63; p=0.07).']

['NeuroSENSE is a depth of anesthesia monitor that uses automated electroencephalogram quantification. The Wavelet-based Anesthetic Value for Central Nervous System (WAVCNS) index calculated by this monitor is based on wavelet analysis of a normalized electroencephalogram signal in the γ-frequency band. The aim of this study was to determine the extent of disagreement between the Bispectral Index (BIS) and the WAVCNS index during propofol-based and sevoflurane-based maintenance of general anesthesia in a routine surgical population.', 'Patients undergoing elective surgery were enrolled in the study and randomly assigned to receive either propofol or sevoflurane for the maintenance of anesthesia and remifentanil in both groups. Anesthesiologists were blinded to monitors in both groups. Discordance between the 2 monitors was assessed by the count of discrepancy in recommendation (DR) (type 1 defined as one parameter <40 and the other >60, or type 2 defined as BIS and WAVCNS values on different sides of a threshold [40 or 60]) and also by the proportion of agreement (P0) between WAVCNS and BIS, obtained every 5 seconds, in 3 categories of index (<40, 40-60, and >60).', 'The analyzed data set consisted of 22 patients (36,872 data pairs) in the propofol group and 24 patients (32,826 data pairs) in the sevoflurane group. The type 1 DR rarely occurred in both the groups (<1%); however, the median (interquartile range) type 2 DR was significantly more frequent in the propofol group (20.6% [7.0-36.9] vs 4.5% [2.3-12.4]; P = 0.0005). The median difference in P0 was 11.53% (95% confidence interval, 0.57-21.32). Major disagreement between WAVCNS index and BIS was related to the weight of burst suppression pattern for the index calculation.']

['The aim of this study was to compare early and mid-term outcome in patients undergoing off-pump coronary artery bypass surgery who have had complete revascularizations and incomplete revascularizations (IRs).', 'Patient and operative data were collected prospectively for all patients who had off-pump coronary artery bypass surgery. Patients with multivessel disease were classified as having IR if the number of diseased coronary systems (left anterior descending coronary artery, circumflex and right coronary artery) exceeded the number of distal anastomoses. In-hospital outcomes, survival, and event-free survival were compared between patients with complete revascularization and IR using propensity scores to take account of differences in prognostic factors.', 'There were 1,479 off-pump coronary artery bypass surgery patients between April 1996 and December 2002 (30% of all coronary artery bypass graft patients), and 16.0% (237 patients) had IRs. Patients with IRs tended to be older and were female, had more extensive disease, worse dyspnea, a higher Parsonnet score, poorer ejection fraction, congestive cardiac failure, asthma or chronic obstructive airways disease, and previous cardiac surgery. The adjusted hazard ratio for patient survival with IRs versus complete revascularizations was 1.56 (95% confidence interval, 1.19 to 2.06; p = 0.001). Analyses for multiple time periods confirmed that IRs had a significantly increased risk of death, but also that the risk disappeared after the first 4 to 6 months of follow-up (p < 0.0001).']

['Atypical parkinsonism (AP) has a considerable impact on the lives not only of patients but also of their carers. The aim of this study was to develop an instrument for assessing the quality of life (QoL) of carers of patients with AP.', 'A 40-item pool was generated from in-depth interviews with carers of patients with AP, a thorough review of the existing literature and consultation with movement disorder experts. Item refinement and reduction was performed using the results of pilot testing and a survey in 282 carers of multiple system atrophy (MSA) patients and 226 carers of progressive supranuclear palsy (PSP) patients. A validation study, with responses of 243 carers of MSA and 187 carers of PSP patients, was undertaken to evaluate the psychometric properties of the final 26-item scale.', "The validation study results suggest that the scale is unidimensional and has high internal consistency (Cronbach's α\xa0=\xa00.96). The correlations of scale scores with patients' health status and QoL measures, such as PDQ-39 summary score and EQ-5D index (Spearman's ρ\xa0=\xa00.56 and -0.31, respectively, P\xa0<\xa00.001), as well as carers' measures, such as Caregiver Burden Inventory (CBI) total and EQ-5D index (Spearman's ρ\xa0=\xa00.85 and -0.39, respectively, P\xa0<\xa00.001), document the convergent and concurrent validity of the scale. ANOVA results support the discriminant validity of the scale, as evidenced by its capacity to differentiate between carers with varying levels of self-reported health."]

['We sought to determine whether myocardial contrast echocardiography (MCE) performed before and early after primary coronary stenting (PCS) in patients with acute myocardial infarction (AMI) could predict recovery of resting left ventricular systolic function and contractile reserve.', 'Myocardial contrast echocardiography can be used to assess perfusion within the risk area before PCS and the extent of necrosis soon after PCS.', 'In 30 patients with AMI, MCE and two-dimensional echocardiography were performed before PCS and 3 to 5 days and 4 weeks after PCS. Contractile reserve was assessed by dobutamine echocardiography at four weeks in patients with persistent severe wall-motion abnormalities.', 'Of segments without perfusion at 3 to 5 days, 95% had severe hypokinesis to akinesis at 4 weeks. Of segments with normal perfusion at 3 to 5 days, 90% had normal wall motion or mild hypokinesis at 4 weeks, whereas those with partial perfusion at 3 to 5 days were evenly divided between normal wall motion, hypokinesis, and akinesis. In segments with persistent severe wall-motion abnormalities at four weeks, contractile reserve was found in >80% of segments with perfusion, compared with only 10% of segments without detectable perfusion (p < 0.01). The presence of myocardial perfusion by MCE before PCS was associated with maintained or improved perfusion at 3 to 5 days and eventual recovery of resting wall motion.']

['Hepatitis C virus (HCV) infection is associated with type II cryoglobulinemia. HCV is specifically concentrated in type II cryoglobulins and has been implicated in the cutaneous vasculitis associated with the disease. In contrast to HCV, a role for hepatitis G virus (HGV) in type II cryoglobulinemia has not been defined, although prevalences as high as 43% of HGV infections in type II cryoglobulinemia have also been reported.', 'We studied 34 patients with type II and 29 patients with type III cryoglobulinemia associated with HCV infection, 6 patients with essential mixed cryoglobulinemia (EMC; all with type II), 50 hospital control patients, and 125 normal individuals. Serum HCV and HGV RNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). In coinfected sera, HCV and HGV were quantitated by competitive RT-PCR assays. One coinfected patient was studied longitudinally for 6 years.', 'Two (5.9%) of 34 patients with HCV-infected type II cryoglobulinemia, none of 29 patients with type III cryoglobulinemia, and none of 6 patients with EMC were positive for HGV RNA, for an overall prevalence of 3.0% in mixed cryoglobulinemia. None of the control populations were positive for HGV. No statistical difference was seen between the prevalence in patients with type II cryoglobulinemia and the other populations studied. In coinfected sera, HCV, but not HGV, was concentrated in cryoglobulins, and HCV, but not HGV, correlated with cryoglobulinemia in a longitudinal study.']

['There is conflicting evidence regarding the educational level and its importance for social and occupational functioning in bipolar disorder (BD). The aim of this study was to investigate how educational achievement relates to function in BD compared with the general population, and which clinical factors are associated with level of education.', 'Hospitalized patients with DSM-IV BD (N=257; 69.3% BD I; 25.7% BD II; 5.1 BD NOS; 51.4% females) were consecutively recruited from mental health clinics throughout Norway and compared with a geographically matched reference sample from the general population (N=56,540) on levels of education, marital status, income, and disability benefits. Further analyses of association were carried out using logistic regression analyses.', 'A significantly higher proportion of subjects in the BD group than in the reference group was single, had low income, or was disabled. No between-group difference was found in educational level. In the reference group education was inversely correlated with the risk of being disabled, but no such relationship was found in the BD group. Rapid cycling and recurring depressive episodes were the only clinical characteristics associated with low educational level.']

['The μ-opioid receptor has been characterized as the main mediator of opioid signalling in neuronal cells. Opioid-induced pain suppression was originally proposed to be mediated by μ-opioid receptor-induced inhibitory effects on cAMP, which is known to mediate inflammatory hypernociception. Recent investigations revealed PI3Kγ and Akt (PKB) as additional elements of μ-opioid receptor signalling. Hence, we investigated the interaction between pronociceptive cAMP and antinociceptive PI3K/Akt signalling pathways.', 'The human neuroblastoma cell line SK-N-LO and primary dorsal root ganglia (DRG) cells from mice were used to elucidate mediators of μ-opioid receptor signalling. In both cellular systems cAMP was manipulated by stimulation of adenylate cyclase and consequent effects on PI3K/Akt signalling were analysed.', 'Morphine stimulated Akt phosphorylation on Ser(473) and Thr(308) in a dose- and time-dependent manner indicating a functional μ-opioid receptor/Akt signalling pathway in μ-SK-N-LO cells. This effect of morphine was suppressed by the μ-opioid receptor inhibitor, naloxone, Pertussis toxin, an inhibitor of Gi heterotrimeric G-proteins, and the pan PI3K inhibitor wortmannin. cAMP-elevating agents also suppressed μ-opioid receptor-dependent stimulation of PI3Kγ lipid kinase and Akt activities in SK-N-LO cells and DRG.']

['Soluble CD163 (sCD163) is a new marker of obesity-related metabolic complications. sCD163 and CD163 mRNA were investigated in relation to the fat distribution at baseline and 12 months after Roux-en-Y gastric bypass (RYGB).', 'Thirty-one obese subjects (BMI: 42.3\u2009±\u20094.7 kg/m(2)) were enrolled. Subcutaneous (SAT) and visceral adipose tissue (VAT) volume were determined by MRI, intrahepatic lipid content (IHL) by MR-spectroscopy, and body composition by DXA. Fasting blood samples and adipose tissue samples were obtained, and ELISA and RT-PCR were performed.', 'RYGB-induced weight loss (36\u2009±\u200911 kg) was accompanied by a significant reduction in sCD163 (2.1\u2009±\u20090.8 mg/l vs. 1.7\u2009±\u20090.7 mg/l), SAT, VAT, and IHL (all, P\u2009<\u20090.001). At baseline, sCD163 was associated with VAT (r\u2009=\u20090.40, P\u2009<\u20090.05) but not with SAT or IHL. Moreover, CD163 mRNA was significantly upregulated in VAT compared with SAT at baseline (P\u2009<\u20090.05) and significantly downregulated in SAT after RYGB (P\u2009<\u20090.001). ΔsCD163 was significantly associated with ΔIHL after RYGB compared with baseline (r\u2009=\u20090.40, P\u2009<\u20090.05).']

['We sought to determine whether peer reviewers who attend a formal interactive training session produce better reviews.', "Peer reviewers were invited to attend a formal, 4-hour, highly interactive workshop on peer review. Attendees received a sample manuscript to read and review in writing in advance. The workshop included presentations on analyzing a study and the journal's expectations for a quality review, discussion of the sample manuscript's flaws and how to address them in a review, discussion of the reviews written by the attendees, and discussion of real reviews of other manuscripts illustrating key points. The performance of attendees on the basis of standard editor quality ratings (1 to 5) was assessed for the 2 years after workshop attendance. Control reviewers matched for previous review quality and volume were selected from nonattendees of the workshop. In study 1, all average reviewers received a standard written invitation. In study 2, 75 randomly selected average reviewers were personally and actively recruited with intensive follow-up by means of e-mail and telephone calls in an effort to reduce self-selection bias.", "In study 1, 25 reviewers volunteered for the course, were eligible for study, attended, and were compared with 25 matched control reviewers. Of attendees filling out evaluations, 19% thought it somewhat and 81% thought it very helpful. All thought it would improve their subsequent reviews, and 85% thought it would improve their review ratings. The mean change in rating after the workshop was 0.11 (95% confidence interval [CI] -0.25 to 0.48) for control reviewers and 0.10 (95% CI -0.20 to 0.39) for attendees. In study 2, of 75 reviewers intensively recruited, only 12 (41%) of those who said they would attend did. All of the participants thought the workshop would improve their performance and ratings. Test scores at the end of the workshop improved in 73% of participants compared with scores on pretests. The control reviewers' average rating changed by -0.10 (95% CI -0.49 to 0.29) versus 0.06 (95% CI -0.34 to 0.23) for attendees."]

['Under physiological conditions the blood flow velocity waveform in the umbilical vein (UV) has an even non-pulsating pattern. Pulsations in the UV have been described in human fetuses exposed to chronic hypoxia and heart failure. Current techniques for fetal surveillance during labor and delivery involve a risk of both over- and underestimation of fetal hypoxia. We aimed to examine whether pulsations in the UV appear in the human fetus during suspected intrapartum hypoxia, and if so whether they are associated with increased risk of operative delivery for fetal distress (ODFD).', 'This was a prospective double blind study including 52 normal pregnancies. A Doppler examination of the UV was performed on 26 fetuses with pathological and 26 fetuses with normal cardiotocography (CTG) during labor. Presence or absence of pulsations in the UV were noted and related to perinatal outcome.', 'Pulsations in the UV were seen in eight (30.8%) of the fetuses with pathological CTG, of which six (75%) underwent ODFD. No pulsations were seen in the other 18 (69.2%) fetuses with pathological CTG and these were all delivered without ODFD. No pulsations were seen in the UV in the fetuses with normal CTG and these were all delivered without ODFD. Among the fetuses with pathological CTG, there was an increased risk of ODFD in fetuses with vs. those without pulsations in the UV (P < 0.0001).']

['(5R)-5-Hydroxytriptolide (LLDT-8), an analogue of triptolide, displays lower toxicity compared to triptolide and has comparable immunosuppressive effects. We investigated the anti-inflammatory and neuroprotective effects of LLDT-8 on cerebral ischemia/reperfusion injury.', 'Nitric oxide production from microglia was assessed by measuring the nitrite concentration in the culture medium with Griess reagent. Microglial cells and ischemic brain tissues were examined for the expression of proinflammatory mediators by qPCR and western blot. Infarct volumes were assessed with TTC histology. The TLR4/NF-κB signaling pathway was analyzed with western blot and immunocytochemistry.', 'LLDT-8 significantly reduced infarct sizes and expression of pro-inflammatory cytokines in the ischemic cortex. LLDT-8 inhibited NO release and expression of TNF-α, IL-1β and iNOS in BV-2 microglia and primary microglia treated with LPS. In addition, LLDT-8 suppressed expression of TLR4, degradation of IκBα and nuclear translocation of NF-κB.']

['To evaluate the effects of keratinocyte growth factor (KGF) on intestinal adaptation after resection of 85% of the small intestine and consider its potential application in short bowel syndrome (SBS).', 'Experimental study using a known model of SBS.', 'Thirty male Sprague Dawley rats.', 'Four groups of animals were designated. Two groups underwent 85% resection of the small intestine, while the other two groups were sham-operated, undergoing transection and reanastomosis. Resected and sham-operated groups then received either 3 mg/kg KGF or vehicle subcutaneously daily for 3 days. Gut adaptation was evaluated by measurements of mucosal cellularity and biochemical activity in duodenal, jejunal, and ileal segments.', 'Significant small intestinal growth after bowel resection alone was confirmed in resected versus sham-operated rats. KGF further augmented this growth in the resected animals. Mucosal wet weight of the small intestine increased with resection and was further increased (by 20% or more) with KGF administration. Mucosal thickness, villus length, and crypt depth exhibited similar patterns of response. The KGF-induced increase in mucosal morphology was accompanied by increased mucosal DNA and protein content, followed by a trend toward increased mucosal enzyme activity. Histology demonstrated an increase in goblet cells in KGF-treated animals. In situ hybridization analysis demonstrated that KGF markedly increased mucosal expression of intestinal trefoil protein (ITF) mRNA.']

['In this study, we investigated the effect of (-)-epigallocatechin-3-gallate (EGCG) on cyclic nucleotide production and vasodilator-stimulated phosphoprotein (VASP) phosphorylation in collagen (10 µg/mL)-stimulated platelet aggregation.', "Washed platelets (10(8)/mL) from Sprague-Dawley rats (6-7 weeks old, male) were preincubated for 3 min at 37°C in the presence of 2 mM exogenous CaCl(2) with or without EGCG or other materials, stimulated with collagen (10 µg/mL) for 5 min, and then used for the determination of intracellular cytosolic Ca(2+) ([Ca(2+)](i)), thromboxane A(2) (TXA(2)), adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and VASP phosphorylation.", 'EGCG dose-dependently inhibited collagen-induced platelet aggregation by inhibiting both [Ca(2+)](i) mobilization and TXA(2) production. Of two aggregation-inhibiting molecules, cAMP and cGMP, EGCG significantly increased intracellular levels of cAMP, but not cGMP. EGCG-elevated cAMP level was decreased by SQ22536, an adenylate cyclase inhibitor, but not by etazolate, a cAMPspecific phosphodiesterase inhibitor. In addition, EGCG elevated the phosphorylation of VASP-Ser(157), a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-Ser(239), a cGMP-dependent protein kinase substrate, in intact platelets and collagen-induced platelets, and VASP-Ser(157) phosphorylation by EGCG was inhibited by both an adenylate cyclase inhibitor SQ22536 and an A-kinase inhibitor Rp-8-Br-cAMPS. We have demonstrated that EGCG increases cAMP via adenylate cyclase activation and subsequently phosphorylates VASP-Ser(157) through A-kinase activation to inhibit [Ca(2+)](i) mobilization and TXA(2) production on collagen-induced platelet aggregation.']

['The primary objective of this study was to determine the feasibility of ultrasound-guided femoral nerve blocks in elderly patients with hip fractures in the emergency department (ED). The secondary objective was to examine the effectiveness of this technique as an adjunct for pain control in the ED.', 'This prospective observational study enrolled a convenience sample of 13 patients with hip fractures. Ultrasound-guided femoral nerve block was performed on all participants. To determine feasibility, time to perform the procedure, number of attempts, and complications were measured. To determine effectiveness of pain control, numerical rating scores were assessed at baseline and at 15 minutes, 30 minutes, and hourly after the procedure for 4 hours. Summary statistics were calculated for feasibility measures. Wilcoxon matched-pairs signed-rank tests and Friedman analysis of variance test were used to compare differences in pain scores.', 'The median age of the participants was 82 years (range, 67-94 years); 9 were female. The median time to perform the procedure was 8 minutes (range, 7-11 minutes). All procedures required only one attempt; there were no complications. After the procedure, there were 44% and 67% relative decreases in pain scores at 15 minutes (P < or = .002) and at 30 minutes (P < or = .001), respectively. Pain scores were unchanged from 30 minutes to 4 hours after the procedure (P < or = .77).']

['Prep1 and Pbx2 are the main homeodomain DNA-binding proteins of the TALE (three amino acid loop extension) family expressed in the thymus. We previously reported reduced Pbx2 expression and defective thymocyte maturation in Prep1 hypomorphic mice. To further investigate the role of this homeodomain DNA-binding protein in T cell development, we generated transgenic mice expressing the N-terminal fragment of Pbx1 (Pbx1NT) under the control of the Lck proximal promoter.', 'Pbx1NT causes Prep1 cytosolic sequestration, abolishes Prep1-dependent DNA-binding activity and results in reduced Pbx2 expression in developing thymocytes. Transgenic thymi reveal increased numbers of CD4(-) CD8(-) CD44(-) (DN3 and DN4) thymocytes, due to a higher frequency of DN2 and DN4 Pbx1NT thymocytes in the S phase. Transgenic thymocytes however do not accumulate at later stages, as revealed by a normal representation of CD4/CD8 double positive and single positive thymocytes, due to a higher rate of apoptotic cell death of DN4 Pbx1NT thymocytes.']

['Iron deficiency (ID) is prevalent, particularly among women of reproductive age (WRA). How mild ID without anemia relates to cognition is poorly understood. Executive functioning (EF) has emerged as potentially being affected by mild ID in WRA.', 'We sought to examine how iron markers relate to performance on EF tasks in nonanemic WRA.', 'Participants included 127 females aged 18-35 y. Hematological indicators included hemoglobin, RBC distribution width, transferrin saturation (TSAT), ferritin, transferrin receptor (TfR), and total body iron (TBI). EF was assessed using 5 tasks. Associations between EF outcomes and iron status were examined using continuous iron predictors and group comparisons.', 'Better iron status was associated with better attention [faster reaction time (RT) with lower TfR (P = 0.028) and higher TSAT (P = 0.013)], inhibitory control [lower RT variability with higher TSAT (P = 0.042) and planning ability (faster planning time and a smaller planning time increase with increasing difficulty with higher ferritin; P = 0.010)]. No associations with iron status were found for several EF outcomes, possibly due to performance ceilings. Paradoxically, worse performance on a working memory task was related to better iron status, which may reflect hippocampal-frontal interference [lower capacity with lower TfR (P = 0.034) and higher TBI (P = 0.043) and a larger accuracy change with increasing difficulty with higher TBI (P = 0.016)]. Longer RTs on a working memory task were observed among those with positive TBI (iron surplus; P = 0.021) and <2 abnormal iron markers (P = 0.013) compared with those with negative TBI (iron deficit) and ≥2 abnormal markers, respectively.']

['The reported mortality reduction of emergency endovascular aneurysm repair (eEVAR) compared with open repair in patients with a ruptured abdominal aortic aneurysm (rAAA), as observed in observational studies, might be flawed by selection bias based on anatomical suitability for eEVAR. In the present study, we compared mortality in EVAR suitable versus non-EVAR-suitable patients with a ruptured AAA who were all treated with conventional open repair.', 'In all patients presenting with a suspected rAAA, computed tomography angiography (CTA) scanning was performed. All consecutive patients with a confirmed rAAA on preoperative CTA scan and treated with open repair between April 2002 and April 2008 were included. Anatomical suitability for eEVAR was determined by two blinded independent reviewers. Outcomes evaluated were mortality (intra-operative, 30-day, and 6-month), morbidity, complications requiring re-intervention and length of hospital stay.', 'A total of 107 consecutive patients presented with a rAAA and underwent preoperative CTA scanning. In 25 patients, eEVAR was performed. In the 82 patients who underwent open repair, CTA showed an EVAR-suitable rAAA in 33 patients (41.8%) and a non-EVAR-suitable rAAA in 49 patients. Thirty-day and 6-month mortality rate was 15/33 (45.5%; 95% confidence interval (CI) 28.1-63.7) and 18/33 (54.5%; 95% CI 36.4-71.9) in the EVAR-suitable group versus 24/49 (49.0%; 95% CI 34.4-63.7) (P=0.75) and 29/49 (59.2%; 95% CI 44.2-73.0) (P=0.68) in the non-EVAR-suitable group, respectively.']

['Emergency department (ED) visits for ambulatory care sensitive conditions (ACSCs) are common among older adults. The high-intensity telemedicine model of care has been proposed as an innovative approach to expand access to acute illness care, thereby preventing ED visits. The aim of this study was to assess the effect of a high-intensity telemedicine program for senior living community (SLC) residents on the rate of ED use for ACSCs.', 'We performed a prospective cohort study at a primary care geriatrics practice that provides care to 22 SLCs. Six SLCs selected as intervention facilities, with the remaining SLCs serving as controls. Consenting practice patients at intervention facilities could have patient-to-provider, real-time, or store-and-forward high-intensity telemedicine services to diagnose and treat illnesses. The primary outcome was the rate of ED visits for which the primary diagnosis was an "ambulatory-care-sensitive" condition by the Institute of Medicine, which we compared between control and intervention participants.', 'During the study period, control participants had 310 ED visits for ACSCs, for a rate of 0.195 visits/person-year. Intervention participants visited the ED for ACSCs 85 times, for a rate of 0.138 visits/person-year [unadjusted rate ratio (RR): 0.71, 95% confidence interval (CI): 0.53-0.94]. Among intervention participants, ED use for ACSCs decreased at an annual rate of 34% (RR: 0.661, 95% CI: 0.444-0.982), whereas, in the control group there was no statistically significant change in ED use over time (RR: 1.01, 95% CI: 0.90-1.14).']

['Many studies have demonstrated that microRNA-21 (miR-21) acts as an oncogene in the tumourigenesis of a variety of tumours and may be involved in the chemotherapeutic drug resistance of tumour cells. In this study, we utilized the leukaemia cell line K562 as an in vitro cell model to investigate whether miR-21 is involved in X-ray irradiation resistance.', 'Retroviral transduction and antisense oligonucleotide transfection were used to overexpress or knock down miR-21 expression, respectively. An MTT assay was used to measure cell viability, and western blotting was performed to detect the expression of the miR-21 target gene, PTEN (phosphatase and tensin homologue), and its downstream signalling components, phosphatidylinositol 3-kinase (PI3K), and AKT.', 'The overexpression of miR-21 decreased the protein expression levels of PTEN, increased the phosphorylation level of AKT, and enhanced the X-ray irradiation resistance in K562 cells. In contrast, the knockdown of miR-21 increased the PTEN protein expression, reduced the phosphorylation levels of the AKT, and increased the sensitivity of K562 cells to X-ray irradiation. The overexpression of PTEN or the knockdown of AKT also increased the sensitivity of K562 cells to X-ray irradiation.']

['To evaluate the prognostic value of L-type amino acid transporter 1 (LAT1) in patients with stage I non-small cell lung cancer (NSCLC).', 'A total of 282 consecutive patients with completely resected pathological stage I NSCLC were retrospectively reviewed. Expression of LAT1 and proliferative activity, as determined by the Ki67 labelling index, were also evaluated immunohistochemically and correlated with the prognosis of patients after complete resection of the tumour. LAT1 expression was positive in 114 patients (40%) [19% of adenocarcinoma (36 of 186 patients), 83% of squamous cell carcinoma (73 of 88 patients) and 63% of large cell carcinoma (five of eight patients)]. There was a significant correlation between LAT1 expression and Ki67 labelling index (gamma = 0.6935, P < 0.001). LAT1 expression was significantly associated with gender, disease stage and pathological features. The 5-year survival rate of LAT1+ patients (69.1%) was significantly worse than that of LAT1- patients (89.4%; P < 0.001). Multivariate analysis confirmed that positive expression of LAT1 was an independent factor for predicting a poor prognosis.']

['This study aims to investigate the association between insulin resistance (IR) and silent lacunar infarction (SLI) in healthy adults.', 'We recruited 2326 healthy Korean adults who took health checkups, including a brain magnetic resonance imaging. SLI was defined as an infarction measuring 0.3 to 1.5 cm in diameter that was localized in the territory of perforating branches of cerebral arteries, as seen in the brain magnetic resonance imaging. The homeostasis model assessment-estimated insulin resistance index was used for IR estimation, and the cutoff value for its diagnosis for Koreans was 2.56.', 'The mean age of the study population was 56.2 years (range, 40-79 years), and 1279 subjects (55.0%) were male. The prevalence of SLI and IR was 8.1% and 18.1%, respectively. In multivariate logistic analysis, after adjusting for traditional SLI-associated risk factors, IR was positively associated with the prevalence of SLI (adjusted odds ratio, 1.69; 95% confidence interval, 1.16-2.46). The proportion of subjects with multiple SLI lesions (≥2) was also higher in the IR (+) group than that in the IR (-) group (4.3% versus 1.7%; P<0.001). In ordered logistic regression, IR was positively associated with an increase in SLI severity (adjusted odds ratio, 1.76; 95% confidence interval, 1.21-2.56).']

['Sepsis has been shown to induce the expansion of CD4+CD25+ regulatory T cells (Tregs), and this paradoxical immune suppression has been suggested to be closely associated with the development of sepsis-induced organ dysfunction. In the present study, we aimed to investigate the possible link between immune suppression and the development of septic acute kidney injury (AKI).', 'We prospectively enrolled patients with a diagnosis of sepsis, with or without AKI and as well as patients with AKI but without sepsis. Serum and urine samples at the time of the diagnosis were collected to measure neutrophil gelatinase-associated lipocalin (NGAL), cytokines, and soluble CD25 (sCD25).', 'Of the 82 patients enrolled, 44, 18, and 20 patients were classified into septic-AKI, sepsis-non AKI and non-septic AKI groups. There were no differences in the baseline characteristics in all three groups and the severity of infection in the two sepsis groups. Serum levels of interleukin (IL)-10 were significantly elevated in patients with septic-AKI compared to the other two groups. Serum and urine NGAL levels and the level of serum sCD25, a marker of regulatory T cells, were significantly elevated in patients with septic AKI group, indicating the potential association of paradoxical immune suppression and the development of septic-AKI.']

['The nature of wheezing after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) is usually transient. However, some children will develop persistent or late wheezing.', 'We hypothesized that early and late postbronchiolitis wheezing are determined by distinct clinical, immunologic, and genetic variables.', 'A cohort of 101 children hospitalized for RSV LRTI was prospectively followed for 6 years. During RSV LRTI, cytokine studies were performed and genetic polymorphisms were determined. Parents performed daily log registration of respiratory symptoms during the first 3 years of follow-up and again at age 6 years during the winter season.', 'Distinctive associations for early and late postbronchiolitis wheezing were found. We previously showed that airflow limitation during RSV LRTI as well as convalescent monocyte IL-10 production are associated with early wheezing. These variables were not associated with late wheezing. On the other hand, atopic family history was not associated with early wheezing, but it was associated with late wheezing. Most importantly, the IL-13 Gln allele was associated with late wheezing (odds ratio 3.27, 95% confidence interval 1.32-8.06), but it was not associated with early wheezing.']

['To assess the effect of endotoxin on cytochrome aa3 (Caa3) redox status in a controlled blood flow preparation of pig isolated hindlimb, at a constant oxygen delivery (Do2limb) (constant flow period) and during progressive ischemia (decreasing flow period).', 'Randomized, controlled experimental study.', 'University hospital experimental laboratory.', 'Ten piglets.', 'Hindlimb blood flow was restricted to the femoral vessels. The arterial femoral blood flow coming from the carotid artery was controlled by a roller occlusive pump. The femoral venous blood flow was returned to the jugular vein. During the first 100 mins, the hindlimb blood flow was maintained at a normal level and then decreased stepwise. Animals were randomized to receive 150 microg/kg endotoxin lipopolysaccharide (LPS; n = 5) or saline (control; n = 5).', 'Hindlimb muscle Caa3 redox status was monitored by near-infrared spectroscopy. Hindlimb Do2limb and oxygen consumption (Vo2limb) were calculated. In the LPS group, a rapid reduction of Caa3 redox status was observed after LPS administration, whereas the hindlimb blood flow remained normal with no change in Do2limb and Vo2limb. A progressive simultaneous decrease in Do2limb and Vo2limb was observed during the decreasing flow period with no further reduction in Caa3 redox status. In the control group, no change was observed in Caa3, Do2limb, or Vo2limb during the constant flow period. During the decreasing flow period, Caa3 redox status was reduced as Do2limb and Vo2limb decreased.']

['The aim of this study was to investigate whether the stimulation of monocytic cells with procalcitonin (PCT) results in the release of proinflammatory cytokines. The effects of intravenous immunoglobulin (IVIG) on the production of cytokines from the cells stimulated with PCT were also studied.', 'Cultured monocytic cells [THP-1 cells treated with phorbol myristate acetate or peripheral blood mononuclear cells (PBMCs)] were stimulated with PCT. The protein levels of proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and high mobility group box-1] in the culture supernatants were determined by ELISA kits. The concentration of PCT-specific IgG antibody in IVIG was measured using a specific ELISA.', 'PCT induced the release of cytokines from THP-1 cells in a time- and dose-dependent manner. IVIG inhibited the release of cytokines from the cells stimulated with PCT. It was confirmed that IVIG also inhibited TNF-α release in the same dose range for PBMCs stimulated with PCT. The presence of PCT-specific IgG antibody was detected in the tested IVIG, which might be one of the mechanisms.']

['Internal elastic lamella and elastic lamellae serve as barriers for macromolecular accumulation in vascular wall. The function of internal elastic lamella in atherogenesis induced by shear stress has not been well understood yet. In the present study, internal elastic lamella remodeling and transmural accumulation of macromolecules in the arterial wall under altered shear stress were investigated.', 'The ligation of left distal carotid branches induced low shear stress in the left common carotid artery and high shear stress in the right common carotid artery of rats for 7 days. Fenestrae in internal elastic lamella were assessed by confocal microscopy. Horseradish peroxidase accumulation was determined by its transmural concentration profiles. Fibronectin expression was examined by immunohistologic staining and Western blotting.', 'Low shear stress significantly decreased the percentage of fenestrae area in internal elastic lamella from 15.35% to 8.03% in left common carotid artery, while high shear stress nearly had no influence in right common carotid artery. Comparing with less accumulation of horseradish peroxidase in right common carotid artery, horseradish peroxidase was significantly accumulated in the innermost part of the media, and fibronectin expression increased to 3.3-fold in left common carotid artery.']

['Overexpression of EGFR is one of the most frequently diagnosed genetic aberrations of glioblastoma multiforme (GBM). EGFR signaling is involved in diverse cellular functions and is dependent on the type of preferred receptor complexes. EGFR translocation to mitochondria has been reported recently in different cancer types. However, mechanistic aspects of EGFR translocation to mitochondria in GBM have not been evaluated to date.', 'In the present study, we analyzed the expression of EGFR in GBM-patient derived specimens using immunohistochemistry, reverse-transcription based PCR and Western blotting techniques. In clinical samples, EGFR co-localizes with FAK in mitochondria. We evaluated this previous observation in standard glioma cell lines and in vivo mice xenografts. We further analyzed the effect of human umbilical cord blood stem cells (hUCBSC) on the inhibition of EGFR expression and EGFR signaling in glioma cells and xenografts. Treatment with hUCBSC inhibited the expression of EGFR and its co-localization with FAK in glioma cells. Also, hUCBSC inhibited the co-localization of activated forms of EGFR, FAK and c-Src in mitochondria of glioma cells and xenografts. In addition, hUCBSC also inhibited EGFR signaling proteins in glioma cells both in vitro and in vivo.']

['HIV-1 shedding from the female genital tract is associated with increased sexual and perinatal transmission and has been broadly evaluated in cross-sectional studies. However, few longitudinal studies have evaluated how the immune microenvironment effects shedding.', 'Thirty-nine HIV-1-infected women had blood, cervicovaginal lavage, and biopsies of the uterine cervix taken quarterly for up to 5 years. Cytokines/chemokines were quantified by Luminex assay in cervicovaginal lavage, and cellular phenotypes were characterized using immunohistochemistry in cervical biopsies. Comparisons of cytokine/chemokine concentrations and the percent of tissue staining positive for T cells were compared using generalized estimating equations between non-shedding and shedding visits across all women and within a subgroup of women who intermittently shed HIV-1.', 'Genital HIV-1 shedding was more common when plasma HIV-1 was detected. Cytokines associated with cell growth (interleukin-7), Th1 cells/inflammation (interleukin-12p70), and fractalkine were significantly increased at shedding visits compared with non-shedding visits within intermittent shedders and across all subjects. Within intermittent shedders and across all subjects, FOXP3 T cells were significantly decreased at shedding visits. However, there were significant increases in CD8 cells and proportions of CD8FOXP3 T cells associated with HIV-1 shedding.']

['This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports.', 'Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle.', 'In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports.']

['Chronic heart failure (CHF) is associated with endothelial dysfunction including impaired endothelium-mediated, flow-dependent dilation (FDD). There is evidence for increased radical formation in CHF, raising the possibility that nitric oxide is inactivated by radicals, thereby impairing endothelial function. To test this hypothesis, we determined the effect of the antioxidant vitamin C on FDD in patients with CHF.', 'High-resolution ultrasound and Doppler was used to measure radial artery diameter and blood flow in 15 patients with CHF and 8 healthy volunteers. Vascular effects of vitamin C (25 mg/min IA) and placebo were determined at rest and during reactive hyperemia (causing endothelium-mediated dilation) before and after intra-arterial infusion of N-monomethyl-L-arginine (L-NMMA) to inhibit endothelial synthesis of nitric oxide. Vitamin C restored FDD in patients with heart failure after acute intra-arterial administration (13.2+/-1.7% versus 8.2+/-1.0%; P<.01) and after 4 weeks of oral therapy (11.9+/-0.9% versus 8.2+/-1.0%; P<.05). In particular, the portion of FDD mediated by nitric oxide (ie, inhibited by L-NMMA) was increased after acute as well as after chronic treatment (CHF baseline: 4.2+/-0.7%; acute: 9.1+/-1.3%; chronic: 7.3+/-1.2%; normal subjects: 8.9+/-0.8%; P<.01).']

['Induction of endoplasmic reticulum (ER) stress-mediated apoptosis in cancer cells represents an alternative approach for cancer therapy. The objective of this study was to elucidate whether ethanol extract of the marine brown alga Dictyopteris undulata can induce apoptosis, via ER stress, in human colon adenocarcinoma cells.', 'Anti-proliferative activity was evaluated by the colony forming assay. ER stress response was evaluated using flow cytometry and confocal imaging after Rhod2 and ER tracker staining. The expression of ER stress-related proteins was assessed by Western blotting.', 'D. undulata extract (DUE) inhibited colony forming ability in SW480 cells. Furthermore, DUE induced characteristic signs of ER stress: mitochondrial Ca(2+) overloading, ER staining, expression of ER stress-related proteins, phosphorylation of RNA-dependent protein kinase-like ER kinase and inositol requiring enzyme 1, cleavage of activating transcription factor 6, and induction of the pro-apoptotic factors, CCAAT/enhancer-binding protein-homologous protein (CHOP) and caspase-12. Moreover, down-regulation of CHOP by siCHOP RNA attenuated DUE-induced apoptosis.']

['Metabolic acidosis (MA) adversely affects protein and lipid metabolism as well as endocrine function. Adipose tissue communicates with the rest of the body through synthesis and release adipokines, such as leptin, adiponectin and TNF-alpha. Adiponectin enhances insulin sensitivity and possesses anti-atherogenic and anti-inflammatory properties. Circulating adiponectin correlates inversely with cardiovascular events. It is possible that MA negatively regulates adiponectin contributing to poor patient outcome. The present study investigates the effect of MA on adiponectin in vivo and in vitro.', 'Twenty healthy female volunteers underwent a 7-day course of oral ammonium chloride (NH4Cl)-induced acidosis. Serum adiponectin was determined before and after NH4Cl ingestion. Adipocytes were differentiated from their precursors, human mesenchymal stem cells (hMSCs), in culture. Concentrated HCl was added to the media to lower pH. Adiponectin mRNA and protein were determined at 48 and 96 h by real-time RT-PCR and ELISA, respectively.', 'After a 7-day course of NH4Cl, serum bicarbonate decreased significantly associated with the increase in urine ammonium and titratable acid. Adiponectin decreased significantly from 10,623 to 9723 pg/mL (P<0.005). MA suppressed adiponectin mRNA in hMSC-derived adipocytes at 48 and 96 h (P<0.01). The amount of adiponectin released into the culture media declined corresponding to the mRNA levels (P<0.001). MA did not affect adipocyte triglyceride or protein content.']

['Conditional survival estimates provide useful prognostic information for cancer survivors. The objective of this study was to determine conditional survival estimates for melanoma patients with substages of stage III disease.', 'A retrospective analysis of 760 patients who underwent lymphadenectomy for node-positive melanoma was conducted, and patients were stratified into substages: IIIA, IIIB, and IIIC. The 5-year conditional disease-free survival (DFS) and disease-specific survival (DSS) were calculated following lymphadenectomy using the methods of Kaplan and Meier and were reassessed for survivors on an annual basis. Multivariate Cox regression models were used to calculate adjusted conditional DFS and DSS accounting for age, gender, tumor histology, and extracapsular extension.', 'For patients with IIIA, IIIB, and IIIC disease, 5-year conditional DSS from treatment to year 5 improved from 78% to 90%, 54% to 79%, and 39% to 78%, respectively. For 5-year conditional DFS over the same period, the estimates increased from 65% to 79%, 37% to 81%, and 26% to 92%, respectively. Male patients experienced decreased 5-year conditional DSS and DFS across all substages, with the most pronounced effect on DSS in stage IIIC. Multivariate analysis demonstrated that survival differences among stage IIIC patients based on histologic subtype and extracapsular extension decreased over time.']

['We aimed to study the role of T-bet-positive mononuclear cell infiltration in different compartments of kidney graft tissues in patients with chronic transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and stable graft function.', 'There were 80 living-related renal transplant recipients included (chronic transplant glomerulopathy, n = 28; interstitial fibrosis and tubular atrophy, n = 28; stable graft function, n = 24). Histologic characteristics and scoring for peritubular capillaritis, glomerulitis, interstitial fibrosis and tubular atrophy, and intimal arteritis were performed according to Banff 2007 classification and compared between the groups. Immunohistologic staining was performed for transcription factor T-bet, T-bet mononuclear cells were counted, and T-bet infiltration score was compared between groups.', 'Patients in different groups had similar clinical profiles and human leukocyte antigen mismatches, except the groups differed in serum creatinine and proteinuria. The prevalence and scoring of peritubular capillaritis and glomerulitis were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy (P = .001) and stable graft function (P < .001). Tubulitis was observed in 6 patients (21.4%) with chronic transplant glomerulopathy but no patients with interstitial fibrosis and tubular atrophy. The C4d/donor-specific antibody was positive in 100% patients with chronic transplant glomerulopathy, 0% patients with interstitial fibrosis and tubular atrophy, and 4.1 % patients with stable graft function. Interstitial fibrosis and tubular atrophy was seen in 100% patients who had interstitial fibrosis and tubular atrophy; in patients who had chronic transplant glomerulopathy, 24 patients (85.7%) had interstitial fibrosis and 78.5% patients had tubular atrophy. The degree and severity of T-bet-positive cell infiltration were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy or stable graft function; however, 85% patients with interstitial fibrosis and tubular atrophy also had T-bet-positive infiltration, suggesting a role of T-bet-positive cells in interstitial fibrosis and tubular atrophy.']

['Resuming two lung ventilation (2LV) from one lung ventilation (OLV) has been proven to induce significant oxidative stress, mainly by superoxide release. Although total intravenous anesthesia and inhalational anesthesia are both used in thoracic surgery, different anesthetics may alter the oxidant/antioxidant balance.', 'Thirty patients undergoing thoracic surgery were randomly allocated to the propofol infusion (intravenous) group or isoflurane (inhalational) group after induction and placement of a double lumen endobronchial tube. Reactive oxygen species (ROS) production and total antioxidant status (TAS) were measured during OLV and 2LV manipulations. Blood samples were taken in the lateral position before OLV (T1), immediately before resuming 2LV (T2), and 5 minutes (T3) and 20 minutes (T4) after resuming 2LV, for measurement of ROS.', 'ROS production increased significantly at T3 and T4 in both groups but to a lesser extent in the propofol infusion group. TAS levels increased with time in the propofol group but not in the isoflurane group.']

['To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide high-dose (FEC-HD) neoadjuvant chemotherapy.', 'One hundred twenty patients have been enrolled by nine French centers in this double-blind, parallel-group, vehicle-controlled study to compare at each cycle subcutaneous lenograstim (5 micrograms/kg/d) with placebo given from day 6 to day 15 after the induction chemotherapy (day 1 to day 4, fluorouracil 750 mg/m2 continuous intravenous [IV] infusion; day 2 to day 4, epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push). Four cycles were planned every 3 weeks before locoregional treatment. Patients with febrile neutropenia remained blinded for the subsequent cycles.', 'Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days, respectively, as compared with 5 and 7 days in the placebo group. This translated into a statistically significant reduced incidence of microbiologically documented infections, and a decreased need for rehospitalizations for infectious events and antibiotic use. Clinical objective tumor response rate observed after four cycles was 89.6% and 93%, respectively, in the placebo and treated groups. Mild transient bone and injection-site pain, myelemia, and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim.']

['Extended-release niacin effectively lowers plasma TG levels and raises plasma high-density lipoprotein (HDL) cholesterol levels, but the mechanisms responsible for these effects are unclear.', 'We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to placebo, on the kinetics of apolipoprotein (apo) A-I and apoA-II in HDL, apoB-100 in TG-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), and apoB-48 in TRL in 5 men with combined hyperlipidemia. Niacin significantly increased HDL cholesterol and apoA-I concentrations, associated with a significant increase in apoA-I production rate (PR) and no change in fractional catabolic rate (FCR). Plasma TRL apoB-100 levels were significantly lowered by niacin, accompanied by a trend toward an increase in FCR and no change in PR. Niacin treatment significantly increased TRL apoB-48 FCR but had no effect on apoB-48 PR. No effects of niacin on concentrations or kinetic parameters of IDL and LDL apoB-100 and HDL apoA-II were noted. The addition of lovastatin to niacin promoted a lowering in LDL apoB-100 attributable to increased LDL apoB-100 FCR.']

['This study aimed to improve existing prediction models for age at menopause.', 'We identified all reproductive aged women with regular menstrual cycles who met our eligibility criteria (n\u200a=\u200a1,015) in the Tehran Lipid and Glucose Study-an ongoing population-based cohort study initiated in 1998. Participants were examined every 3 years and their reproductive histories were recorded. Blood levels of antimüllerian hormone (AMH) were measured at the time of recruitment. Age at menopause was estimated based on serum concentrations of AMH using flexible parametric survival models. The optimum model was selected according to Akaike Information Criteria and the realness of the range of predicted median menopause age.', 'We followed study participants for a median of 9.8 years during which 277 women reached menopause and found that a spline-based proportional odds model including age-specific AMH percentiles as the covariate performed well in terms of statistical criteria and provided the most clinically relevant and realistic predictions. The range of predicted median age at menopause for this model was 47.1 to 55.9 years. For those who reached menopause, the median of the absolute mean difference between actual and predicted age at menopause was 1.9 years (interquartile range 2.9).']

['We sought an optimal medial branch block (MBB) cutoff value for both single and double MBB protocols that would best correlate with a positive outcome of medial branch neurotomy (MBN).', "We analyzed the percentage of subjective pain relief following MBB, confirmed by numerical rating scale (NRS) in aggravating positions before and 45 minutes after MBB. The percentage of overall pain relief following MBB was plotted against the following outcome variables: degree of subjective pain relief, duration of relief, patient satisfaction and activity level, no other doctor's visits, and reduction in medications use.", 'Using the percent of pain relief post-MBB plotted in 10% increments in the double-MBB group, patients reporting 70% or greater pain relief following MBB showed statistically favorable outcome for the following four criteria: percentage of pain relief, duration of relief, patient satisfaction, and pain medications reduction. In the single MBB group, patients reporting 80% or greater pain relief following MBB had favorable outcomes for improvement in activity level and patient satisfaction.']

['Cell penetrating peptides (CPPs) can mediate effective delivery of their associated drugs and drug carriers intracellularly, however their lack of cell specificity remains a major obstacle for their clinical development. We aimed at improving the cell specificity and therapeutic efficacy of HPMA copolymer-octaarginine (R8) conjugate (P-R8) in cells at the tumor micro-environment.', 'To avoid premature cell-penetration, the positively charged R8 moieties were masked via electrostatic complexation with various polyanionic molecules (heparin sulfate, hyaluronic acid, fucoidan and poly-glutamic acid). We followed the kinetics of the FITC-labeled P-R8 penetration into endothelial and cancer cells over-time after its complexation in vitro and further tested whether the in situ addition of a stronger polycation can trigger the release of P-R8 from the complexes to resume cell penetration activity. A murine model of B16-F10 lung metastasis was then used as an in vivo model for assessing the therapeutic efficacy of the P-R8, loaded with doxorubicin (P-R8-DOX), after its complexation with PGA.', 'The intracellular penetration of P-R8-FITC was reversibly inhibited by forming electrostatic interactions with counter polyanions, and can be restored either gradually over time by dissociation from the polyanions, or promptly following the addition of protamine sulfate. Mice injected with B16-F10 cells and treated with P-R8-DOX/PGA complexes, exhibited a significant prolonged survival times when compared with DOX-treated mice or relative to mice treated with either P-R8-DOX or P-DOX alone.']

['Chronic hepatitis C is frequently associated with increased hepatic iron stores. It remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. Therefore our aim was to assess associations between HFE mutations and hepatic inflammation and stage of fibrosis in German hepatitis C patients.', 'Liver biopsies from 166 patients were scored for inflammatory activity (A0-4) and hepatic fibrosis (F0-4). Gene mutations were determined by LightCycler, restriction fragment length polymorphism analysis, or direct sequencing.', 'The frequencies of common HFE mutations C282Y and H63D are 4.2% and 21.3%, whereas the recently described S65C substitution and the Y250X mutation in the transferrin receptor 2 gene are very rare. In regression analysis, heterozygous carriers of C282Y or H63D mutations display significantly (P < 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. For C282Y heterozygous patients, the odds ratios for marked inflammatory activity (A2-4) and advanced liver fibrosis or cirrhosis (F2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. C282Y mutations are associated with significantly (P < 0.05) increased serum iron and aminotransferase levels, whereas H63D heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (P < 0.01).']

['Short-term clinical trials suggest that dietary protein lowers blood pressure (BP); however, long-term effects of total, animal, and plant proteins are less clear. Our goal was to evaluate effects of these dietary proteins on mean systolic BP (SBP) and diastolic BP (DBP) and incident high BP (HBP) risk among middle-aged adults in the Framingham Offspring Study.', "Men and women (aged 30-54 years) without prevalent HBP, cardiovascular disease, or diabetes with 3-day dietary records from exams 3 or 5 (n = 1,361) were included and followed for a mean of 11.3 years for development of HBP. Protein intakes adjusted for body size were derived using the residual method. Analysis of covariance and Cox proportional hazard's models were used to adjust for age, sex, education, height, activity, smoking, fat calories, diet quality, and body mass index.", 'Higher protein intakes were associated with lower mean SBP and DBP. Both animal and plant proteins lowered BP and led to statistically significant reductions in HBP risk (hazard ratios of 0.68 and 0.51, respectively). Participants in the highest tertile of total protein intake had 40% less risk (95% confidence interval [CI], 0.45-0.78) of developing HBP. Beneficial effects of protein were apparent for men and women and for normal-weight and overweight individuals. Higher protein diets also characterized by higher fiber intakes led to a 59% reduction (95% CI, 0.37-0.66) in HBP risk.']

['We reported before that, in baboons, the alcohol-induced oxidative stress in the liver is associated with depletion of dilinoleoylphosphatidylcholine [the major component of polyenylphosphatidylcholine (PPC)] and that both can be corrected by the administration of PPC, but we did not determine whether this protection extended to iron-induced oxidative stress.', 'To compare the effects of PPC on alcohol- and iron-induced hepatic oxidative stress, 56 Sprague Dawley male rats were pair-fed nutritionally adequate liquid diets containing ethanol (36% of energy) or isocaloric carbohydrate and PPC (3 mg/ml) or safflower oil (2.73 mg/ml), with or without 5 mg/ml carbonyl iron for 2 months. Markers of oxidative stress (4-hydroxynonenal and reduced glutathione), antioxidants (vitamin E, ubiquinol-9, and ubiquinol-10), and phosphatidylcholine (PC) species were assessed by HPLC and/or gas chromatography/mass spectrometry.', 'Alcohol feeding increased hepatic 4-hydroxynonenal 3-fold and decreased glutathione by 19%, ubiquinol-10 by 53%, and PC species containing arachidonate (palmitoyl- and stearoylarachidonoylphosphatidylcholines by 24% and 21%, respectively) and total phospholipids by 14%. PPC feeding prevented the rise of 4-hydroxynonenal, restored glutathione, and increased the hepatic content of dilinoleoylphosphatidylcholine and of some other PC carrying polyunsaturated fatty acids. Administration of iron alone increased hepatic iron, doubled 4-hydroxynonenal and glutathione, whereas it decreased vitamin E, ubiquinol-9, total phospholipids, and several polyunsaturated PC. Alcohol given with iron further exacerbated the hepatic oxidative stress, as documented by the increase of 4-hydroxynonenal and the decrease in glutathione and ubiquinols-10. PPC did not prevent this oxidative stress, although it increased hepatic glutathione. Hepatic dilinoleoylphosphatidylcholine content was comparable with and without dietary iron.']

['Myocardial infarction (MI) is associated with early metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation. We hypothesized that preserving the original ECM of the infarcted left ventricle (LV) by use of early short-term doxycycline (DOX) treatment preserves cardiac structure and function.', 'LV morphometry and function were measured in 3 groups of rats (sham, MI, and MI+DOX). DOX (30 mg/kg per day) was given orally 48 hours before and 48 hours after MI. Rats were examined at 2 and 4 weeks after MI. By 4 weeks, DOX significantly decreased (P<0.05 versus MI) the heart weight to body weight ratio, myocyte cross-sectional area, and internal LV diameter, whereas it preserved anterior wall thickness within the infarct. Collagen/muscle area fraction did not change in the region of the infarct/scar. Parallel left shifts (versus MI) were observed in pressure-volume relationships of DOX MI rats at all pressures. DOX treatment also shifted passive epicardial strains within the scar area toward normal values. No differences were observed in LV end-diastolic or peak systolic pressures, peak positive or negative LV dP/dt, or isovolumic relaxation rates. Assessment of LV global MMP and MMP-2/9 activities 1 hour after MI using fluorescent probes yielded significant differences with DOX.']

['The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer.', 'Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used.', 'All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients.']

['Warts are thought to be associated with the development of squamous cell carcinoma (SCC) in organ transplant patients. We investigated the association between the different types of warts and SCC in organ transplant patients.', 'A prospective multicenter case-control study was conducted. Cases were patients with a kidney or heart transplant who were referred for a SCC. Controls were organ transplant patients without SCC, individually matched for age, gender, type of organ transplant (heart or kidney), skin phototype, time from transplantation, and center. Four types of warts: flat warts, verrucae vulgares (including palmo-plantar warts and common warts), verrucous papilloma, and verrucokeratotic lesions were compared between cases and controls using conditional logistic regression.', 'Ninety-nine cases and 169 controls were included. In multivariate analysis, number of rejections, azathioprine, prednisolone and anti-lymphocyte anti-serum or anti-CD3 monoclonal antibodies use, cumulative sun exposure, actinic keratosis, and verrucokeratic lesions (odds ratio [OR] 16.50; 95% confidence interval [CI] 2.82-96.80) were independently associated with SCC, whereas the association with verrucous papilloma was borderline significant (OR 2.21; 95% CI 0.97-8.15). The association between the presence of at least one of these two types of warts (verruco-keratotic lesions and verrucous papilloma) and the occurrence of SCC was highly significant (OR 18.36; 95% CI 3.03-111) when these warts were located in the same area than SCC, whereas no significant association was evidenced when these warts were located in another area (OR 1.02; 95% CI 0.13-5.79).']

['The objective of this study was to determine whether amniotic fluid index < or = 5.0 cm or two-diameter pocket volume < or = 15 cm2 is a predictor of abdominal delivery because of fetal distress or of Apgar score < 7 at 1 or 5 minutes.', 'The study was prospective and involved 209 parturients in early labor who had ultrasonographic assessment of amniotic fluid volume by both methods.', 'The incidences of cesarean delivery because of fetal distress and of Apgar scores < 7 at 1 and 5 minutes were 8.1%, 9.0%, and 1.9%, respectively. Only Apgar scores < 7 at 1 minute were significantly higher among patients with a two-diameter pocket < 15 cm2 (16/114) as compared with > 15(2) (3/95, p = 0.007). Oligohydramnios by either method was a poor predictor of adverse outcomes (p values ranging from 0.06 to 0.21). Receiver-operating characteristic curves generated for the amniotic fluid index or two-diameter pocket to predict abdominal delivery because of fetal distress or Apgar scores < 7 at 1 minute indicate that both methods are poor diagnostic tests to predict these complications.']

['The purpose of this study was to investigate the mitochondrial effects exerted by physiological and supra-physiological concentrations of recombinant human growth hormone (rhGH) and recombinant insulin-like growth factor-1 (rIGF-1) under conditions of substrate saturation in peripheral blood mononuclear cells (PBMCs).', 'PBMCs from healthy male subjects were treated with either rhGH, at concentrations of 0.5, 5 and 50\xa0μg/L, or rIGF-1 at concentrations of 100, 300 and 500\xa0μg/L for 4\xa0h. Mitochondrial membrane potential (Δψm) and mitochondrial levels of highly reactive oxygen species (hROS) were subsequently analysed. This analysis was performed by flow cytometry in digitonin permeabilized cells, following treatment with saturating concentrations of various respiratory substrate combinations and the use of specific electron transport chain (ETC.) complex inhibitors, enabling control over both the sites of electron entry into the ETC. at complexes I and II and the entry of electrons from reduced carriers involved in β-oxidation at the level of ubiquinol.', 'Neither rhGH nor rIGF-1 exerted any significant effect on Δψm or the rate of hROS production in either lymphocyte or monocyte sub-populations under any of the respiratory conditions analysed.']

['To compare the effectiveness of 70-mg and 200-mg doses of intravenous erythromycin in improving gastric emptying in critically ill patients.', 'Gastric emptying was measured on consecutive days; day 1 (pre-treatment), day 2 (post-treatment) after an intravenous infusion of either 70 or 200 mg erythromycin or saline placebo (0.9%), in a randomized double-blind fashion.', 'Mixed medical/surgical intensive care unit, tertiary referral.', 'Thirty-five randomly selected, mechanically ventilated, enterally fed critically ill patients (median APACHE II score 19 on admission).', 'On day 2 either 70 or 200 mg erythromycin or saline was administered intravenously over 20 min.', 'Gastric emptying was measured using the [13C]octanoic acid breath test. The gastric emptying coefficient (GEC) and half-emptying time (t1/2) were calculated from the area under the 13CO2-recovery curve. Pre-treatment gastric emptying measurements were similar in all three patient groups. Treatment with both doses of erythromycin significantly reduced the gastric t1/2: 70 mg, 98 min (IQR 88-112); 200 mg, 86 min (75-104); vs. placebo, 122 min (102-190) (p<0.05). The GEC was higher with both doses of erythromycin: 70 mg, 3.8 (3.3-4.0); 200 mg, 4.0 (3.6-4.2); vs. placebo, 2.9 (2.5-3.7) (p<0.05). There was no difference in gastric emptying post-treatment between the two doses of erythromycin. The effect of erythromycin was greatest in patients with delayed gastric emptying.']

['most fractures are preceded by falls.', 'the aim of this study was to determine whether tests of physical performance are associated with fractures.', 'a total of 10,998 men aged 65 years or above were recruited.', 'questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference.', 'fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture.']

['Histological examination of pre-transplant renal biopsy specimens can be used to select grafts from older donors after cardiac death (DCD) with a satisfactory transplant outcome. The aim was to determine whether such biopsy specimens can be reproducibly scored between pathologists and are representative of the whole kidney.', 'In renal biopsy specimens from DCD aged >or=60 years (n = 44), globally sclerosed glomeruli, vascular narrowing, tubular atrophy and interstitial fibrosis were scored by three independent pathologists according to the Pirani scoring system. Interobserver agreement on the sum of scores improved considerably with the introduction of a combined tubulo-interstitial scoring system (intraclass correlation coefficient increased from 0.38 to 0.64). In small needle biopsy specimens (n = 144) obtained at autopsy, estimates of the proportion of globally sclerosed glomeruli were more precise with increasing sample size. Reasonably precise estimates may be obtained from specimens with at least seven glomeruli.']

['Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response.', 'In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated.', 'A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12).']

['To evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation.', 'Lewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment.', 'Neutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina.']

['The steroid ouabain is found in plasma and in many mammalian tissues, and is now considered as a hormone. In the immune system, ouabain regulates a number of lymphocyte functions, but little is known about its effects on monocyte function. Monocytes are important for adequate immune responses. The aim of this work was to analyze the effect of ouabain on mCD14 expression, a surface molecule involved in the response against Gram-negative bacteria and phagocytosis.', 'Human peripheral blood mononuclear cells obtained from healthy donors were separated by density gradient centrifugation. Monocytes were separated by adherence and treated for 24 h with 100 nM ouabain. mCD14, CD1a and P-p38 expression was analyzed by flow cytometry. Inhibitors of cell-signaling pathways, i.e. SB202190, reduced glutathione, rottlerin, tyrphostin A23, genistein, chelerythrine chloride, PD98059, PP1 and Ly 294002, were used concomitantly with ouabain to observe their effect on mCD14 expression.', 'Ouabain induced a significant decrease in mCD14 expression. This feature was not related to receptor endocytosis or cell death. Furthermore, mCD14 downregulation did not reflect a shift in differentiation into dendritic cells because this hormone failed to induce CD1a expression. Amongst several inhibitors of cell-signaling pathways triggered by ouabain, only epidermal growth factor receptor (EGFR) and p38 mitogen-activated protein kinase (MAPK) inhibitors (tyrphostin A23 and SB202109) significantly reverted the effect of ouabain on mCD14 expression. Accordingly, the levels of P-p38 were increased on monocytes after ouabain treatment. However, incubation with epidermal growth factor did not alter mCD14 expression.']

['Smoking and stress, pancreatic cancer (PanCa) risk factors, stimulate nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and catecholamines production respectively. NNK and catecholamine bind the β-adrenoceptors and induce PanCa cell proliferation; and we have previously suggested that β-adrenergic antagonists may suppress proliferation and invasion and stimulate apoptosis in PanCa. To clarify the mechanism of apoptosis induced by β2-adrenergic antagonist, we hypothesize that blockage of the β2-adrenoceptor could induce G1/S phase arrest and apoptosis and Ras may be a key player in PanCa cells.', 'The β1 and β2-adrenoceptor proteins were detected on the cell surface of PanCa cells from pancreatic carcinoma specimen samples by immunohistochemistry. The β2-adrenergic antagonist ICI118,551 significantly induced G1/S phase arrest and apoptosis compared with the β1-adrenergic antagonist metoprolol, which was determined by the flow cytometry assay. β2-adrenergic antagonist therapy significantly suppressed the expression of extracellular signal-regulated kinase, Akt, Bcl-2, cyclin D1, and cyclin E and induced the activation of caspase-3, caspase-9 and Bax by Western blotting. Additionally, the β2-adrenergic antagonist reduced the activation of NFκB in vitro cultured PanCa cells.']

['Compensatory enlargement of the coronary arterial wall has been described in the early stages of native atherosclerosis. However, little is known about the specific effect of aging on this adaptive process in atherosclerosis. The purpose of the current study was to characterize the effects of advancing age on vascular remodeling and endothelium-dependent and -independent coronary vasodilation in patients without coronary artery disease risk factors.', 'Twenty-six patients without coronary risk factors and with normal and mildly diseased coronary arteries were studied. Vessel, lumen and atherosclerotic plaque areas were evaluated by intravascular ultrasound and coronary flow response was assessed using papaverine and acetylcholine in the left anterior descending coronary artery.', 'There was a weak but significant correlation between plaque area and age (r = 0.29, P<0.01). Vessel area was also weakly but significantly correlated with age (r = 0.22, P<0.05). However, lumen area had no correlation with age. Vessel area in the younger group (<50 years) and the older group (> or =50 years) increased 1.64 and 0.55 mm2 for every 1 mm2 increase in plaque area (r = 0.62, P<0.0001 and r = 0.39, P<0.05, respectively). With regard to vascular reactivity, there was an inverse correlation between the percentage increases in coronary blood flow (CBF) evoked by acetylcholine and aging (r = -0.49, P<0.05). The percentage increases in CBF evoked by papaverine also inversely correlated with aging (r=-0.53, P<0.01). However, the percentage changes in coronary artery diameter evoked with acetylcholine did not correlate with aging.']

['intimal hyperplasia (IH) and constrictive remodelling are important causes of restenosis following endovascular interventions, such as percutaneous transluminal angioplasty. Photodynamic therapy (PDT) with 5-aminolaevulinic (ALA) may prevent restenosis by cellular depletion and the elimination of cholinergic innervation.', 'rats (n=90) were subdivided into 4 main groups. In the experimental group (n=36: 3 replications x 4 doses x 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633nm at either 12.5, 25, 50 or 100J/cm diffuser length (dl BI+PDT group). As control groups served the BI+Light only (LO) group (n=36) that received no ALA, the BI only group (n=9) (BI), and a group (n=9) that received a Sham procedure (Sham group).', 'planimetric analysis showed IH of 0.28+/-0.12mm(2) (BI), 0.27+/-0.12mm(2) (BI+LO at 100J/cmdl) in contrast to 0.02+/-0.02mm(2) after BI+PDT at 100J/cmdl at 16 weeks (p<0.05). In the BI+PDT groups, a light-dose increase of a factor 2 led to an IH decrease of 17% (p<0.05). In the BI and BI+LO groups constrictive remodelling was found, in contrast to BI+PDT treated groups at 16 weeks. The staining of cholinergic innervation of the tunic media of the blood vessel wall in BI+PDT showed no damage at the highest fluence.']

['Peripheral blood biomarkers are needed to identify and determine the extent of idiopathic pulmonary fibrosis (IPF). Current physiologic and radiographic prognostic indicators diagnose IPF too late in the course of disease. We hypothesize that peripheral blood biomarkers will identify disease in its early stages, and facilitate monitoring for disease progression.', 'Gene expression profiles of peripheral blood RNA from 130 IPF patients were collected on Agilent microarrays. Significance analysis of microarrays (SAM) with a false discovery rate (FDR) of 1% was utilized to identify genes that were differentially-expressed in samples categorized based on percent predicted D(L)CO and FVC.', 'At 1% FDR, 1428 genes were differentially-expressed in mild IPF (D(L)CO >65%) compared to controls and 2790 transcripts were differentially- expressed in severe IPF (D(L)CO >35%) compared to controls. When categorized by percent predicted D(L)CO, SAM demonstrated 13 differentially-expressed transcripts between mild and severe IPF (< 5% FDR). These include CAMP, CEACAM6, CTSG, DEFA3 and A4, OLFM4, HLTF, PACSIN1, GABBR1, IGHM, and 3 unknown genes. Principal component analysis (PCA) was performed to determine outliers based on severity of disease, and demonstrated 1 mild case to be clinically misclassified as a severe case of IPF. No differentially-expressed transcripts were identified between mild and severe IPF when categorized by percent predicted FVC.']

['Interferon lambda 3 (IFN-λ3) is a newly identified cytokine with antiviral activity, and its single nucleotide polymorphisms are strongly associated with the treatment effectiveness and development of chronic hepatitis C virus infection. We thus examined the potential of IFN-λ3 to inhibit HIV replication and the possible mechanisms of the anti-HIV action by IFN-λ3 in human macrophages.', 'Under different conditions (before, during, and after HIV infection), IFN-λ3 significantly inhibited viral replication in macrophages, which was associated with the induction of multiple antiviral cellular factors (ISG56, MxA, OAS-1, A3G/F and tetherin) and IFN regulatory factors (IRF-1, 3, 5, 7 and 9). This anti-HIV action of IFN-λ3 could be compromised by the JAK-STAT inhibitor. In addition, IFN-λ3 treatment of macrophages induced the expression of toll-like receptor 3 (TLR3) and two key adaptors (MyD88 and TRIF) in type I IFN pathway activation. However, HIV infection compromised IFN-λ3-mediated induction of the key elements in JAK-STAT signaling pathway.']

['Asporin is a novel extracellular matrix protein (ECM) with an important role in the development of osteoarthritis (OA), because it has been reported that functional polymorphisms in the aspartic acid repeat (D) of the asporin gene (ASPN) are associated with susceptibility to OA.', 'This study was planned to investigate the association of the ASPN polymorphism with primary OA of the knee in a Mexican population, including several countryside regions.', 'We conducted a case-control study in which 93 cases with primary OA of the knee and 118 controls were included. Cases included patients > 40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee of ≥ 2. Controls were subjects > 40 years of age with a radiologic score of < 2. The D repeat polymorphism was genotyped and logistic regression was developed to evaluate risk magnitude.', 'The D14 allele was more common in our cases and was associated with an increased risk for developing OA, while the frequencies of the remaining alleles did not exhibit differences.']

['Ovarian cancer is the most lethal gynecological malignancy in North America. Although survival rates are high when the disease is diagnosed at an early stage, this decreases exponentially in late-stage diagnoses. As such, there is a need for novel early detection biomarkers. Through an integrated approach to ovarian cancer biomarker discovery that combines proteomics with transcriptomics and bioinformatics, our laboratory has identified folate-receptor 1 (FOLR1) and Dickkopf-related protein 3 (Dkk-3) as putative biomarkers. The objective of this study was to measure the levels of FOLR1 and Dkk-3 in the serum of patients with ovarian cancer, benign gynecological conditions and healthy women.', 'FOLR1 and Dkk-3 were analyzed in serum of 100 ovarian cancer patients, 100 patients with benign gynecological conditions, and 100 healthy women using enzyme-linked immunosorbent assays (ELISAs). All specimens were analyzed in triplicate.', 'FOLR1 was significantly elevated in the serum of ovarian cancer patients compared to serum of both healthy controls (P<0.0001) and patients with benign gynecological conditions (P<0.0001). Furthermore, FOLR1 was strongly correlated with CA125 as both were elevated in the serous histotype and in late-stage disease. FOLR1 did not outperform CA125 in receiver operating characteristic curve analysis and there was no significant complementarity between the two markers. Dkk-3 was not significantly different between the three serum cohorts and was not correlated with CA125.']

['Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF.', 'A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities.', 'There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years.']

['There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role.', 'We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring.', 'In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information.', 'Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively.']

['Heat shock protein 27 (HSP27) is a cytoprotective chaperone, activated by stressful stimuli. HSP27 modulates aggregation and degradation of many proteins. Recent evidence suggests that HSP27 could be involved in the progression of tumor growth and in the development of resistance of various tumors to chemo- and radiotherapy. It has been reported that melatonin protects pancreatic cells and various tissues against inflammatory damage. Previous experimental studies have shown that melatonin stimulates pancreatic enzyme secretion and improves the outcome of experimental pancreatitis. To investigate whether melatonin could affect HSP27 protein level in human pancreatic carcinoma cells (PANC-1). PANC-1 cells were incubated in the standard medium DMEM supplemented with 10% fetal bovine serum at 37 degrees C with 5% CO2 and humidified atmosphere under basal conditions or in the presence of decreasing doses of melatonin (10(-6) - 10(-12)M). Control experiments were performed with the vehicle only (0,1% DMSO) without melatonin. After 24 h and 48 h the cells were harvested, the cytoplasmic and nuclear proteins were isolated for western blot and immunoblotting studies. Incubation of the PANC-1 cells with melatonin resulted in the stimulation both cytoplasmic and nuclear nonphosphorylated HSP27 protein levels after 24 h of incubation, however, above pools of nonphosphorylated chaperone protein levels were strongly diminished after subsequent 24 h. These changes were accompanied by marked rise of nuclear phosphorylated HSP27. The significant increase of this nuclear protein was observed after 48h of incubation.']

['The endopeptidase dipeptidyl peptidase-IV (DPP-IV) has been shown to NH2-terminally truncate incretin hormones, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1, thus ablating their ability to potentiate glucose-stimulated insulin secretion. Increasing the circulating levels of incretins through administration of DPP-IV inhibitors has therefore been introduced as a therapeutic approach for the treatment of type 2 diabetes. DPP-IV inhibitor treatment has also been shown to preserve islet mass in rodent models of type 1 diabetes. The current study was initiated to define the effects of the DPP-IV inhibitor sitagliptin (MK0431) on transplanted islet survival in nonobese diabetic (NOD) mice, an autoimmune type 1 diabetes model.', 'Effects of MK0431 on islet graft survival in diabetic NOD mice were determined with metabolic studies and micropositron emission tomography imaging, and its underlying molecular mechanisms were assessed.', 'Treatment of NOD mice with MK0431 before and after islet transplantation resulted in prolongation of islet graft survival, whereas treatment after transplantation alone resulted in small beneficial effects compared with nontreated controls. Subsequent studies demonstrated that MK0431 pretreatment resulted in decreased insulitis in diabetic NOD mice and reduced in vitro migration of isolated splenic CD4+ T-cells. Furthermore, in vitro treatment of splenic CD4+ T-cells with DPP-IV resulted in increased migration and activation of protein kinase A (PKA) and Rac1.']

['To investigate the rate of spontaneous passage of single and symptomatic common bile duct (CBD) stones ≤ 10 mm in diameter in 4 wk with or without a 2-wk course of anisodamine.', 'A multicenter, randomized, placebo-controlled trial was undertaken. A total of 197 patients who met the inclusion criteria were enrolled. Ninety-seven patients were assigned randomly to the control group and the other 100 to the anisodamine group. The anisodamine group received intravenous infusions of anisodamine (10 mg every 8 h) for 2 wk. The control group received the same volume of 0.9% isotonic saline for 2 wk. Patients underwent imaging studies and liver-function tests every week for 4 wk. The rate of spontaneous passage of CBD stones was analyzed.', 'The rate of spontaneous passage of CBD stones was significantly higher in the anisodamine group than that in the control group (47.0% vs 22.7%). Most (87.2%, 41/47) stone passages in the anisodamine group occurred in the first 2 wk, and passages in the control group occurred at a comparable rate each week. Factors significantly increasing the possibility of spontaneous passage by univariate logistic regression analyses were stone diameter (< 5 mm vs ≥ 5 mm and ≤ 10 mm) and anisodamine therapy. Multivariate logistic regression analyses revealed that these two factors were significantly associated with spontaneous passage.']

['Using high resolution magnetic resonance imaging, we detected severely underdeveloped trabecular bone microarchitecture in the distal femur of children with cerebral palsy who can not ambulate independently vs. typically developing controls. Furthermore, very good short-term reliability of trabecular bone microarchitecture measurements was observed in both groups of children.', 'Severe forms of cerebral palsy (CP) are associated with very low areal bone mineral density and a very high incidence of fracture in the distal femur; however, the state of trabecular bone microarchitecture has not been evaluated. Furthermore, the short-term reliability of trabecular bone microarchitecture assessment in children using high-resolution magnetic resonance imaging (MRI) has not been determined.', 'Apparent bone volume to total volume (appBV/TV), trabecular number, (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp) were determined in the distal femur of non-ambulatory children with CP and typically developing children using MRI.', 'Children with CP had a 30% lower appBV/TV, a 21% lower appTb.N, a 12% lower appTb.Th and a 48% higher appTb.Sp in the distal femur than controls (n = 10/group; P < 0.001). The short-term reliability of the trabecular bone microarchitecture measures was very good, with coefficients of variation ranging from 2.0 to 3.0% in children with CP (n = 6) and 1.8 to 3.5% in control children (n = 6).']