Datasets:

316usman

/

pubmedqa_train_cleaned

like 0

{ "CONTEXT": "As more patients are treated by haematopoietic stem cell transplantation (HSCT), development of secondary malignancy (SM) becomes an increasingly common issue in long-term survivors. We conducted a nationwide population-based study of the Taiwanese population to analyse patients who received HSCT between January 1997 and December 2010. Standardised incidence ratios (SIRs) were used to compare the risk of SM in HSCT patients and the general population. Multivariate analysis was performed to identify independent predictors of SM. Patients receiving HSCT had a significantly greater risk of developing SM (SIR 2.00; 95% confidence interval (CI) 1.45-2.69; P<0.001). Specifically, the incidence increased for cancers of the oral cavity (SIR 14.18) and oesophagus (SIR 14.75) after allogeneic HSCT. Multivariate analysis revealed an increased SIR for cancer in patients who received the immunosuppressant azathioprine. The risk of SM also increased with greater cumulative doses of azathioprine.", "LONG_ANSWER": "This study demonstrates an increased incidence of SM in Taiwanese patients who received allogeneic HSCT, especially for cancers of the oral cavity and oesophagus. This finding is different from results in populations of Western countries. Physicians should be cautious about azathioprine use for graft-vs-host disease after HSCT.", "QUESTION": "Is use of azathioprine for graft-vs-host disease the major risk for development of secondary malignancies after haematopoietic stem cell transplantation : a nationwide population-based study?" }

{ "CONTEXT": "A model of independent, external review of significant event analysis by trained peers was introduced by NHS Scotland in 1998 to support the learning needs of general practitioners (GPs). Engagement with this feedback model has increased over time, but participants' views and experiences are largely unknown and there is limited evidence of its educational impact. This is important if external feedback is to play a potential role in appraisal and future revalidation. The study aimed to explore aspects of the acceptability and educational impact of this external feedback model with participating GPs. Semi-structured interviews were carried out with nine GPs. Participants were sampled to reflect their level of learning need (low, moderate or high) to gain a range of views and experiences. Transcribed interviews were analysed for content. This system of external peer feedback is generally acceptable to participants. It complemented and enhanced the appraisal process. External feedback had positive educational outcomes, particularly in imparting technical knowledge on how to analyse significant events. Training issues for peer reviewers were suggested that would further enhance the educational gain from participation. There was disagreement over whether this type of feedback could or should be used as supporting evidence of the quality of doctors' work to educational and regulatory authorities.", "LONG_ANSWER": "The findings add to the evidence for the acceptability and educational impact of external review by trained peers. Aligning such a model with the current national appraisal system may provide GPs with a more robust demonstration of participation in reflective learning.", "QUESTION": "Do acceptability and educational impact of a peer feedback model for significant event analysis?" }

{ "CONTEXT": "To improve detection and quality of assessment of child and partner abuse within a health service. A formal organisational change approach was used to implement the New Zealand Family Violence Intervention Guidelines in a mid-sized regional health service. The approach includes obtaining senior management support, community collaboration, developing resources to support practice, research, evaluation and training. Formal pre-post evaluations were conducted of the training. Barriers and enablers of practice change were assessed through 85 interviews with 60 staff. More than 6000 clinical records were audited to assess rates of questioning for partner abuse. Identifications of partner abuse and referrals made were counted through the Family Violence Accessory File. Referrals to the Department of Child, Youth and Family Services (CYFS) were recorded routinely by the CYFS. Audits assessed quality of assessment of child and partner abuse, when identified. More than 700 staff were trained in dual assessment for child and partner abuse. Evaluations demonstrate improved confidence following training, though staff still need support. Barriers and enablers to asking about partner abuse were identified. Referrals from the health service to the CYFS increased from 10 per quarter to 70 per quarter. Identification of partner abuse increased from 30 to 80 per 6-month period. Routine questioning rates for partner abuse vary between services.", "LONG_ANSWER": "Achieving and sustaining improved rates of identification and quality of assessment of child and partner abuse is possible with a formal organisational change approach.", "QUESTION": "Is improving detection and quality of assessment of child abuse and partner abuse achievable with a formal organisational change approach?" }

{ "CONTEXT": "To determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation. Prospective, randomized study. Animal laboratory of an institute for research traumatology. Male Sprague-Dawley rats, weighing 450 to 480 g. Anesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg i.v., starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5. The 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group).", "LONG_ANSWER": "These data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats.", "QUESTION": "Does monoclonal antibody to endotoxin attenuate hemorrhage-induced lung injury and mortality in rats?" }

{ "CONTEXT": "Hyperlipidemia associated with the protease inhibitor (PI) component of highly active antiretrovial treatment can lead to accelerated atherosclerosis. The apolipoprotein A-V (APOA5) gene, which affects VLDL production and lipolysis, may play a role in PI-induced hyperlipidemia, particularly in individuals with the APOA5-1131T-->C genotype. We measured lipoprotein changes in HIV-positive patients (n = 229) who had been followed for 5 years. For statistical analyses, we segregated the patients with respect to PI treatment and APOA5-1131T-->C genotype. The frequency of the C allele was 0.08, similar to that in the general population. We found a strong effect of the APOA5-1131T-->C genotype among patients receiving PIs. Carriers of the C allele had consistently increased mean (SD) triglyceride concentrations compared with noncarriers after 1 year [2.11 (1.62) vs 3.71 (4.27) mmol/L; P = 0.009], 2 years [2.48 (2.09) vs 4.02 (4.05) mmol/L, P = 0.050], 3 years [2.32 (1.71) vs 4.13 (4.26) mmol/L; P = 0.013], 4 years [2.90 (2.95) vs 5.35 (7.12) mmol/L; P was not significant], and 5 years [4.25 (5.58) vs 9.23 (9.63) mmol/L; P was not significant]. We observed the same effect on total cholesterol concentrations: after 1 year [4.93 (1.31) vs 5.87 (1.66) mmol/L; P = 0.006], 2 years [5.03 (1.12) vs 6.42 (2.48) mmol/L; P = 0.001], 3 years [5.11 (1.17) vs 6.38 (2.43) mmol/L; P = 0.009], 4 years [5.49 (1.71) vs 6.78 (3.03) mmol/L; P was not significant], and 5 years [5.56 (1.75) vs 7.90 (3.60) mmol/L; P was not significant]. HDL cholesterol showed a progressive reduction, leading to a considerably higher cholesterol/HDL cholesterol ratio after 3 years.", "LONG_ANSWER": "Variability in the APOA5 gene predisposes patients with HIV, particularly those treated with PI, to severe hyperlipidemia.", "QUESTION": "Is protease inhibitor-associated dyslipidemia in HIV-infected patients strongly influenced by the APOA5-1131T- > C gene variation?" }

{ "CONTEXT": "We previously demonstrated that tenascin-C was highly expressed in the fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR). However, its role in the pathogenesis of FVMs has not been determined. The purpose of this study was to investigate what role tenascin-C plays in the formation and angiogenesis of FVMs. The level of tenascin-C was determined by sandwich enzyme-linked immunosorbent assay in the vitreous samples collected from patients with PDR and with a macular hole as control. The locations of tenascin-C, α- smooth muscle actin (SMA), CD34, glial fibrillary acidic protein (GFAP), and integrin αV in the FVMs from PDR patients were determined by immunohistochemistry. We also measured the in vitro expression of the mRNA and protein of tenascin-C in vascular smooth muscle cells (VSMCs) stimulated by interleukin (IL)-13. The effects of tenascin-C on cell proliferation, migration, and tube formation were determined in human retinal endothelial cells (HRECs) in culture. The mean vitreous levels of tenascin-C were significantly higher in patients with PDR than in patients with a macular hole (p<0.001). Double immunofluorescence analyses of FVMs from PDR patients showed that tenascin-C co-stained FVMs with α-SMA, CD34, and integrin αV but not with GFAP. In addition, IL-13 treatment increased both the expression and secretion of tenascin-C by VSMCs in a dose-dependent manner. Tenascin-C exposure promoted proliferation, migration, and tube formation in HRECs. Tenascin-C neutralizing antibody significantly blocked the tube formation by HRECs exposed to VSMC-IL-13-conditioned medium.", "LONG_ANSWER": "Our findings suggest that tenascin-C is secreted from VSMCs and promotes angiogenesis in the FVMs associated with PDR.", "QUESTION": "Does tenascin-C promote angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy?" }

{ "CONTEXT": "Progressive hepatocarcinogenesis is a stepwise process that drives liver transformation. However, the molecular mechanisms of early liver transformation are far from clear. A role for microRNAs (miRNA) as diagnostic and prognostic factors in human tumours, including hepatocellular carcinoma (HCC), is promising. We aimed to identify novel miRNA as biomarkers for differential diagnosis and predictors of disease progression. We used a low-density array platform to profile the expression of 664 mature miRNA in a cohort of 60 hepatitis C virus-positive liver lesions representative of all stages of progressive hepatocarcinogenesis. We validated selected miRNA in two independent patient series by qPCR and we characterized the genomic status of the miRNA cluster C19MC by fluorescent in situ hybridization and copy-number variation analyses. A 18-miRNA signature distinguished cirrhosis, dysplastic nodules and HCC lesions. Four miRNAs overexpressed in HCCs belonged to chromosome 19 miRNA cluster (C19MC). Significant overexpression of C19MC in early HCC compared to dysplastic nodules could be confirmed in a second series of hepatitis B virus-related liver lesions (n = 30). In a third series of 61 HCCs, C19MC cluster was overexpressed in HCCs compared to matched cirrhotic parenchyma and regardless of the type of viral infection. High C19MC miRNA levels were correlated with poor clinico-pathological features, increased risk of tumour recurrence and shorter overall survival time. HCCs overexpressing the C19MC cluster showed genetic amplification of the corresponding locus.", "LONG_ANSWER": "C19MC cluster is a novel molecular alteration characteristic of liver cancer and predictor of poor prognosis. C19MC is an attractive candidate for novel HCC therapies.", "QUESTION": "Does microRNA profiling of hepatocarcinogenesis identify C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Increased CpG methylation of cccDNA is associated with old age, low serum HBV DNA levels and suppressed replicative activity in HBV-LC.", "QUESTION": "Is replicative activity of hepatitis B virus negatively associated with methylation of covalently closed circular DNA in advanced hepatitis B virus infection?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The molecular detection of carcinoembryonic antigen messenger RNA in the preoperative peripheral blood is an independent prognostic factor in patients with non-small cell lung cancer who undergo a curative operation.", "QUESTION": "Is preoperative evidence of circulating tumor cells by means of reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen messenger RNA an independent predictor of survival in non-small cell lung cancer : a prospective study?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Our results suggested that common genetic variants related to vitamin D levels are not associated with risk of ESCC in this Chinese population.", "QUESTION": "Are common genetic variants related to vitamin D status associated with esophageal squamous cell carcinoma risk in China?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "The stage-IIB category is comprised of eight sub-categories, with either single factors or factor combinations; these sub-categories have different prognoses. The worst survivals were for cases with T2bN1M0 as a single factor or for cases with multiple factors, although these represented a small proportion of resected stage-IIB NSCLC cases.", "QUESTION": "Do single T factors predict survival of patients with resected stage-IIB non-small-cell lung cancers?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Overexpression of LEF1 is a favorable prognostic factor in childhood ALL. The prognostic impact of LEF1 may assist treatment stratification and suggest the need of alternative regimens.", "QUESTION": "Is overexpression of lymphoid enhancer-binding factor-1 ( LEF1 ) a novel favorable prognostic factor in childhood acute lymphoblastic leukemia?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "This experiment supports previous studies in humans suggesting a link between calcium intake during pregnancy and blood pressure in the offspring, and provides an animal model to explore the mechanisms involved in such association.", "QUESTION": "Does a deficient maternal calcium intake during pregnancy increase blood pressure of the offspring in adult rats?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "ZA is effective against experimental MPE, suggesting that this intervention should be considered for testing in clinical trials.", "QUESTION": "Is zoledronic acid effective against experimental malignant pleural effusion?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The expression of MMP-9 in the follicular fluid and culture media is a prerequisite for successful pregnancy in IVF cycle. The zymography of MMP-9 activity in follicular fluids of human and culture media was developed as a pre-diagnostic method and zymographic diagnosis marker for successful fertilisation, implantation and pregnancy in human IVF.", "QUESTION": "Is the expression of matrix metalloproteinase-9 in human follicular fluid associated with in vitro fertilisation pregnancy?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.", "QUESTION": "Does scavenger receptor CD36 expression contribute to adipose tissue inflammation and cell death in diet-induced obesity?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.", "QUESTION": "Is hypercalciuria associated with high dietary protein intake due to acid load?" }

{ "CONTEXT": "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 % (n = 301) of all surveillance colonoscopies performed. Among the premature cases, rationale was attributed to inadequate bowel preparation in 17.3 % (n = 52) and due to a new clinical indication in 21.6 % (n = 65). Most commonly, in 61.1 % (n = 184) of premature cases, no rationale was documented for the early colonoscopy.", "LONG_ANSWER": "Documented decision-making rationale for premature surveillance colonoscopy is usually absent in premature cases with inadequate bowel preparation and new clinical indications explaining only a minority of the occurrences.", "QUESTION": "Is most Premature Surveillance Colonoscopy Attributable to Bowel Preparation or New Clinical Indications?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Plasma MMP-8 concentration is associated with the presence and severity of CAD.", "QUESTION": "Are plasma matrix metalloproteinase-8 concentrations associated with the presence and severity of coronary artery disease?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These findings suggest that enhanced reactivity to stress is associated with higher hormone levels among postmenopausal women, which could have potential implications for health.", "QUESTION": "Is psychological reactivity to laboratory stress associated with hormonal responses in postmenopausal women?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Topical immunotherapy with DPCP is an effective and preferred method in the treatment of periungual warts.", "QUESTION": "Is topical immunotherapy with diphenylcyclopropenone effective and preferred in the treatment of periungual warts?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen.", "QUESTION": "Does surfactant Protein D modulate allergen particle uptake and inflammatory response in a human epithelial airway model?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.", "QUESTION": "Is protection against infarction afforded by preconditioning mediated by A1 adenosine receptors in rabbit heart?" }

{ "CONTEXT": "Abdominal pain of functional origin is very common in childhood, and environmental factors are thought to be of aetiologic importance. The anthroposophic lifestyle has dietary and lifestyle characteristics that may influence child health, and this study aimed to assess the effect of such lifestyles on abdominal pain of functional origin. A prospective Swedish lifestyle cohort (n = 470) was followed from birth to five years of age. Family lifestyles were characterised through questionnaires. Abdominal pain was defined as irritable bowel syndrome or functional abdominal pain according to the Rome III criteria and measured with parental questionnaires and interviews at the age of five. The prevalence of abdominal pain was 15%. Children were more likely to have abdominal pain at five years of age if their family had a partly anthroposophic lifestyle, with an adjusted odds ratio (OR) of 2.61 (95% CI 1.15-5.93), or an anthroposophic lifestyle, with an adjusted OR of 2.34 (95% CI 0.96-5.70).", "LONG_ANSWER": "A family lifestyle with anthroposophic characteristics was associated with an increased risk of abdominal pain in five-year-old children. The mechanisms for this increase were unclear, but we speculate that there may have been different prerequisites for coping with stressors.", "QUESTION": "Are irritable bowel syndrome and functional abdominal pain in five-year-old children related to lifestyle?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "In this study, the response to the different drug classes differed. The response to drugs that work relatively nonspecifically (diuretics, calcium blockers) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems. This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day.", "QUESTION": "Do different drug classes have variable effects on blood pressure depending on the time of day?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Part of the asthma process might involve T cell-dependent airway narrowing with no requirement for IgE, mast cells, or infiltrating inflammatory cells.", "QUESTION": "Are late asthmatic reactions provoked by intradermal injection of T-cell peptide epitopes associated with bronchial mucosal infiltration of eosinophils or T ( H ) 2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These findings demonstrate that hypoxia-induced abnormal calpain activation may increase ER stress-induced apoptosis in AD pathogenesis. In contrast, a reduction in the expression of the m-calpain isoform reduces ER stress-linked apoptosis that is triggered by hypoxia. These findings suggest that hypoxia-triggered m-calpain activation is involved in ER stress-mediated AD pathogenesis. m-calpain is a potential target for AD therapeutics.", "QUESTION": "Does hypoxia-triggered m-calpain activation evoke endoplasmic reticulum stress and neuropathogenesis in a transgenic mouse model of Alzheimer 's disease?" }

{ "CONTEXT": "Gemcitabine is a drug commonly used to treat pancreatic cancer but chemoresistance to it is a common clinical issue. KML001 (sodium meta-arsenite) has demonstrated certain antitumor activity. The objective of the study was to evaluate the influence of KML001 on the anticancer activity of gemcitabine against pancreatic cancer cells. Cell proliferation, migration, and invasion were assessed, as well as the expression of nuclear factor-kappa B (NF-κB) p65, epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP2), and vascular endothelial growth factor-C (VEGFC) in pancreatic cancer cells. Treatment with a combination of KML001 and gemcitabine resulted in significant inhibition of cell proliferation, migration, and invasion, and significantly reduced EGFR and MMP2 expression compared to gemcitabine treatment-alone.", "LONG_ANSWER": "Combination treatment of gemcitabine and KML001 could be an effective chemotherapeutic treatment for pancreatic cancer.", "QUESTION": "Does kML001 enhance anticancer activity of gemcitabine against pancreatic cancer cells?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Our data suggest that S1P(3) mediates the chemotactic effect of S1P in macrophages in vitro and in vivo and plays a causal role in atherosclerosis by promoting inflammatory monocyte/macrophage recruitment and altering smooth muscle cell behavior.", "QUESTION": "Does sphingosine-1-phosphate receptor 3 promote recruitment of monocyte/macrophages in inflammation and atherosclerosis?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "This work demonstrates the utility of exome sequencing to rapidly screen heterogeneous genetic disorders such as the ataxias. Exome sequencing is more comprehensive, faster, and significantly cheaper than conventional Sanger sequencing, and thus represents a superior diagnostic screening tool in clinical practice.", "QUESTION": "Does exome sequencing in an SCA14 family demonstrate its utility in diagnosing heterogeneous diseases?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "A large class teaching activity, framed as a simulation of a natural disaster is an acceptable and effective activity for medical students to develop the non-technical skills of collaboration, negotiation and communication, which are essential to team working. The design could be of value in medical schools in disaster prone areas, including within low resource countries, and as a feasible intervention for learning the non-technical skills that are needed for patient safety.", "QUESTION": "Do a large-scale mass casualty simulation to develop the non-technical skills medical students require for collaborative teamwork?" }

{ "CONTEXT": "To document the preoperative core temperature of adult elective surgical patients. A prospective audit obtained sublingual temperatures from 446 adult elective surgical patients on arrival in the preoperative holding area. Temperatures ranged from 35.7 degrees C to 37.8 degrees C with a mean of 36.5 degrees C (0.4 SD). The median was 36.4 degrees C and the mode was 36.1 degrees C. There was a skewed distribution with a clustering of values at the lower end of the range. All recordings were within the accepted normothermic range.", "LONG_ANSWER": "The asymmetric distribution we observed differs from previously published normothermia data which shows a symmetrical distribution of temperatures. This skewed distribution has not previously been documented and we interpret it as being due to the effect of preoperative cooling factors.", "QUESTION": "Do preoperative core temperatures in elective surgical patients show an unexpected skewed distribution?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Jingjielianqiao Decoction and Shengjiyuhong Decoction can obviously promote the healing of leg ulcer in rabbits.", "QUESTION": "Does [ Jingjielianqiao Decoction promote leg ulcer healing in rabbits ]?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "ACE deletion polymorphism is strongly and independently associated with coronary atherosclerosis and, to a lesser extent, with myocardial infarction. As such, the results are analogous to what has already been reported in French white, Japanese, and Welsh coronary patients.", "QUESTION": "Is angiotensin converting enzyme gene deletion allele independently and strongly associated with coronary atherosclerosis and myocardial infarction?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Polar coordinates can be applied to cephalometry to accurately and integrally describe maxillofacial profile features. There are minor differences between the profile features of beautiful men and women, and the differences are mainly shown in mandible and the fullness of lips.", "QUESTION": "Does [ An analysis of soft tissue profile features of beautiful men and women with polar coordinate ]?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Alternative splicing and potentially other editing mechanisms generate ASC isoforms with distinct abilities to function as inflammasome adaptor, which is potentially utilized to regulate inflammasomes during the inflammatory host response.", "QUESTION": "Does differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain ( ASC ) regulate inflammasomes?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "We demonstrated, for the first time, that breast cancer cell CD44v4 is a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers. This finding offers new insights into the molecular basis of E-selectin-dependent adhesive interactions that mediate breast cancer cell transendothelial metastasis.", "QUESTION": "Is cD44v4 a major E-selectin ligand that mediates breast cancer cell transendothelial migration?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These results indicate that hysterectomy status (with or without BLO) is associated with greater arterial stiffening in estrogen-deficient postmenopausal women. The greater arterial stiffening with hysterectomy was not related to an adverse CVD risk profile. Large artery stiffening may be an important mechanism by which hysterectomy increases the risk of CVD in postmenopausal women.", "QUESTION": "Is hysterectomy associated with large artery stiffening in estrogen-deficient postmenopausal women?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "RF of lungs from NHBD improves graft function by elimination of microthrombi from the pulmonary vasculature, resulting in lower pulmonary vascular resistance upon reperfusion.", "QUESTION": "Does retrograde flush following warm ischemia in the non-heart-beating donor result in superior graft performance at reperfusion?" }

{ "CONTEXT": "To find sustainable alternatives to the application of synthetic chemicals for oomycete pathogen suppression. Here, we present experiments on an Arabidopsis thaliana model system in which we studied the antagonistic properties of rhizobacterium Paenibacillus polymyxa strains towards the oomycete plant pathogens Phytophthora palmivora and Pythium aphanidermatum. We carried out studies on agar plates, in liquid media and in soil. Our results indicate that P. polymyxa strains significantly reduced P. aphanidermatum and P. palmivora colonization in liquid assays. Most plants that had been treated with P. polymyxa survived the P. aphanidermatum inoculations in soil assays.", "LONG_ANSWER": "The antagonistic abilities of both systems correlated well with mycoidal substance production and not with the production of antagonistic substances from the biocontrol bacteria.", "QUESTION": "Does paenibacillus polymyxa antagonize oomycete plant pathogens Phytophthora palmivora and Pythium aphanidermatum?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity.", "QUESTION": "Are pro-inflammatory cytokines elevated in adolescent females with emotional disorders not treated with SSRIs?" }

{ "CONTEXT": "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 ± 10 years) with STEACS (n = 95) or NSTEACS (n = 131) 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 ± 3 months and 60 ± 10 months 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 = 0.018). Multivariate analysis showed that the independent predictors of CP between the second and final CAGs were NSTEACS (odds ratio 2.709, P = 0.003), estimated glomerular filtration rate <60 ml/min/1.73 m", "LONG_ANSWER": "Irrespective of conventional risk factors and angiographic findings, ST-segment category at initial presentation is associated with the persistency of widespread coronary disease activity following presentation in ACS patients undergoing PCI. This may partly explain the time-dependent differences in outcomes of patients with STEACS and NSTEACS.", "QUESTION": "Is sT-segment category at acute presentation associated with the time course of coronary artery disease progression in patients with acute coronary syndromes?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "GHH can be managed safely and effectively laparoscopically, without the use of a prosthesis.", "QUESTION": "Is laparoscopic repair of giant hiatus hernia : prosthesis required for successful outcome?" }

{ "CONTEXT": "To investigate the presence of rmpA and wcaG virulence genes and Class 1, 2, and 3 integrons, and to evaluate a relationship between antibiotic resistance and virulence in Klebsiella pneumoniae METHODS: We collected a total of 200 K. pneumoniae isolates from hospitals in Tehran, Iran. Antibiotic susceptibility was determined using the disk diffusion method. The extended-spectrum β-lactamase (ESBL) producers were detected using the combination disk method. We detected the rmpA and wcaG genes and class 1, 2, and 3 integrons via polymerase chain reaction (PCR). The χ Of 200 isolates, 115 (57.5%) were ESBL producers; 74.0% carried the class 1 integron, and 1.0% carried the class 2 integron. The gene rmpA was detected in 7% of isolates and the gene wcaG in 23.5% of isolates. Integron-positive isolates showed a higher prevalence of wcaG compared with to integron-negative isolates (P <.05).", "LONG_ANSWER": "Our results showed a correlation between presence of virulence gene and antibiotic resistance in K. pneumoniae.", "QUESTION": "Does association Between Presence of Virulence Genes and Antibiotic Resistance in Clinical Klebsiella Pneumoniae isolate?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "The single troponin measurement at hospital admission in patients with decompensated HF predicts adverse outcomes and should be considered at the early stratification of long-term morbimortality.", "QUESTION": "Does [ Single cardiac troponin T measurement predict risk for adverse outcome in decompensated heart failure ]?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Disagreement between BIS and NeuroSENSE during the maintenance of general anesthesia was worse in the propofol group than that in the sevoflurane groups. The disagreement increases during deep anesthesia or in the occurrence of burst suppression.", "QUESTION": "Does a Randomized Controlled Trial Comparison of NeuroSENSE and Bispectral Brain monitor During Propofol-Based Versus Sevoflurane-Based General Anesthesia?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Compared with off-pump coronary artery bypass surgery patients with complete revascularizations, those with IRs have reduced survival, but only in the first 4 to 6 months after surgery. Patients' preoperative condition, rather than IR itself, may explain these findings because IRs should have mid-term as well as early effects.", "QUESTION": "Is incomplete revascularization during OPCAB surgery associated with reduced mid-term event-free survival?" }

{ "CONTEXT": "Hematopoietic stem cells (HSCs) are defined by their capacity to self-renew and to differentiate into all blood cell lineages, and are currently the foundation of HSC transplantation therapy. A variety of methods have recently been explored to find a way to expand hematopoietic stem and progenitor cells (HSCs/PCs) ex vivo in order to improve the efficiency and outcome of HSC transplantation. Recent studies of HSCs/PCs have led to the development of new ways to detect and purify HSCs/PCs and have also revealed several intrinsic and extrinsic factors that control the molecular signals fundamental to self-renewal and differentiation of HSCs. These findings have provided new approaches for expanding HSCs/PCs ex vivo utilizing protein factors and small-molecule compounds (SMCs) and have also demonstrated promising outcomes in clinical trials.", "LONG_ANSWER": "Although further technical innovation is still needed, elucidation of the whole picture of signaling pathways critical to HSCs/PCs and manipulation of such pathways by SMCs could establish efficient, cost-effective, riskless and robust methods for ex vivo expansion of HSCs/PCs. With these efforts, more sophisticated HSC transplantation would be possible in the near future.", "QUESTION": "Does new approach to expand hematopoietic stem and progenitor cells?" }

{ "CONTEXT": "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 = 0.96). 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 = 0.56 and -0.31, respectively, P < 0.001), as well as carers' measures, such as Caregiver Burden Inventory (CBI) total and EQ-5D index (Spearman's ρ = 0.85 and -0.39, respectively, P < 0.001), 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.", "LONG_ANSWER": "The 26-item Parkinsonism Carers QoL (PQoL Carer) is a concise instrument with adequate psychometric qualities that can be used for clinical and research purposes.", "QUESTION": "Do development and validation of a carers quality-of-life questionnaire for parkinsonism ( PQoL Carers )?" }

{ "CONTEXT": "Leptin is an adipocyte secreted hormone involved in regulation of body weight and metabolism in man. Placenta leptin levels correlate positively with birth weight. It is therefore possible that variation in the leptin receptor gene (LEPR) may contribute to obesity and influence birth weight. This study investigates the influence of the leptin receptor gene variant Gln223Arg (A-->G, 668), on maternal body mass index (BMI), foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian (India, Bangladesh, Pakistan) and UK/Irish origin. Maternal genotype distributions did not differ from those expected under Hardy-Weinberg equilibrium conditions in either population of origin. Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no significant association with foetal birth weight (adjusted for gestational length) or with maternal BMI during first trimester (adjusted for age) in either population group.", "LONG_ANSWER": "These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight, and is not associated with variation in maternal BMI in early pregnancy in our sample.", "QUESTION": "Is maternal leptin receptor gene variant Gln223Arg associated with variation in birth weight or maternal body mass index in UK and South Asian populations?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Myocardial contrast echocardiography performed early after PCS provides information on the extent of infarction, and hence the likelihood for recovery of resting systolic function or contractile reserve. The presence of perfusion before PCS, from either collateral or antegrade flow, predicts the maintenance of perfusion and recovery of systolic function.", "QUESTION": "Does detection of myocardial viability by contrast echocardiography in acute infarction predict recovery of resting function and contractile reserve?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "There is a low prevalence of coinfection with HGV in patients with mixed cryoglobulinemia and HCV infection in the United States. HCV is selectively precipitated by type II cryoglobulins in coinfected sera. HGV infection does not appear to have a role in mixed cryoglobulinemia.", "QUESTION": "Does hepatitis C virus but not GB virus C/hepatitis G virus have a role in type II cryoglobulinemia?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Acutely admitted patients might not be representative for milder forms of disease.", "QUESTION": "Do bipolar disorder patients have similar levels of education but lower socio-economic status than the general population?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The data unveil a hitherto unknown interaction of pronociceptive cAMP and antinociceptive PI3K/Akt signalling pathways in neuronal cells. PI3Kγ was identified as a mediator of the inhibitory action of cAMP on Akt in SK-N-LO cells and DRG. The data indicate that PI3Kγ has a critical role in cAMP-mediated inflammatory hypernociception and analgesic signalling via μ-opioid receptors and PI3K/Akt in neuronal cells.", "QUESTION": "Does pI3Kγ integrate cAMP and Akt signalling of the μ-opioid receptor?" }

{ "CONTEXT": "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 ± 4.7 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 ± 11 kg) was accompanied by a significant reduction in sCD163 (2.1 ± 0.8 mg/l vs. 1.7 ± 0.7 mg/l), SAT, VAT, and IHL (all, P < 0.001). At baseline, sCD163 was associated with VAT (r = 0.40, P < 0.05) but not with SAT or IHL. Moreover, CD163 mRNA was significantly upregulated in VAT compared with SAT at baseline (P < 0.05) and significantly downregulated in SAT after RYGB (P < 0.001). ΔsCD163 was significantly associated with ΔIHL after RYGB compared with baseline (r = 0.40, P < 0.05).", "LONG_ANSWER": "RYGB-induced weight loss results in a reduction of sCD163 and CD163 mRNA. The association between ΔsCD163 and ΔIHL may reflect a reduction in sCD163-producing Kupffer cells in the liver. Moreover, sCD163 may be a marker of \"unhealthy\" fat distribution in obese subjects.", "QUESTION": "Does intrahepatic fat content correlate with soluble CD163 in relation to weight loss induced by Roux-en-Y gastric bypass?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Among invited peer reviewers, voluntary attendance at a highly structured and interactive workshop was low and did not improve the quality of subsequent reviews, contrary to the predictions of attendees. Efforts to aggressively recruit average reviewers to a second workshop were time consuming, had low success rates, and showed a similar lack of effect on ratings, despite improvement in scores on a test instrument. Workshop teaching formats, although traditional, are of unproven efficacy.", "QUESTION": "Do effect of structured workshop training on subsequent performance of journal peer reviewers?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Pulsations in the UV can be observed in human fetuses during suspected intrapartum hypoxia and these pulsations are associated with an increased risk of ODFD. Doppler examination of the UV might give important additional information on fetal condition during labor and delivery.", "QUESTION": "Are pulsations in the umbilical vein during labor associated with increased risk of operative delivery for fetal distress?" }

{ "CONTEXT": "(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.", "LONG_ANSWER": "LLDT-8 exerted anti-inflammatory effects and protected against acute cerebral ischemia/reperfusion injury possibly by acting through the IκB/NF-κB cascade to suppress microglia-mediated neuroinflammation.", "QUESTION": "Does lLDT-8 protect against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "KGF enhances gut growth, differentiation, and gene regulation during adaptation in rat small intestine after massive resection.", "QUESTION": "Does keratinocyte growth factor enhance early gut adaptation in a rat model of short bowel syndrome?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These results strongly indicate that EGCG is a beneficial compound elevating cAMP level in collagen-platelet interaction, which may result in the prevention of platelet aggregation-mediated thrombotic diseases.", "QUESTION": "Does epigallocatechin-3-gallate have an anti-platelet effect in a cyclic AMP-dependent manner?" }

{ "CONTEXT": "Even moderate increases in levels of homocysteine cause cardiovascular degeneration. Various genetic and nutritional factors affect plasma homocysteine concentrations, and hyperhomocysteinemia damages vascular endothelial cells; hence their functions are disrupted. In diabetes mellitus, homocysteine metabolism is altered and as a result, more severe diabetic complications are expected when hyperhomocysteinemia occurs. In the present study we experimentally induced diabetes in rats and examined effects of low or high dose of insulin administration on homocysteine metabolism. We determined that homocysteine levels were reduced in STZ-induced diabetic rats. This reduction was normalized by insulin in a dose-dependent manner. On the other hand, increased levels of lipid parameters (cholesterol, triglycerides, HDL) were reduced by insulin.", "LONG_ANSWER": "Hcy level in experimentally induced insulin-dependent diabetes mellitus is decreased and injection of insulin normalizes Hcy levels in a dose-dependent manner. We speculate that insulin increases activities of enzymes of transsulfuration and remethylation reactions and hence speeds up conversion of Hcy to methionine and cysteine.", "QUESTION": "Does insulin increase homocysteine levels in a dose-dependent manner in diabetic rats?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Ultrasound-guided femoral nerve blocks are feasible to perform in the ED. Significant and sustained decreases in pain scores were achieved with this technique.", "QUESTION": "Does ultrasound-guided femoral nerve block in elderly patients with hip fractures?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The results obtained by genetic (Prep1 hypomorphic) and functional (Pbx1NT transgenic) inactivation of Prep1 support nonredundant roles for this homeodomain protein during different stages of T cell development.", "QUESTION": "Does cytosolic sequestration of Prep1 influence early stages of T cell development?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These findings suggest cognitive ramifications of mild ID in otherwise healthy WRA and have implications for daily well-being. Future investigators should explore how brain system interactions change according to iron availability.", "QUESTION": "Does iron Status be Associated with Performance on Executive Functioning Tasks in Nonanemic Young Women?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The present study suggests that anatomical suitability for EVAR is not associated with lower early and midterm mortality in patients treated with open ruptured AAA repair. Therefore, the reported reduction in mortality between eEVAR and open repair is unlikely due to selection bias based on anatomical AAA configuration.", "QUESTION": "Is eVAR suitability a predictor for early and midterm mortality after open ruptured AAA repair?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Providing acute illness care by high-intensity telemedicine to older adults residing in SLCs significantly decreases the rate of ED use for ACSCs over 1 year, compared with no change in the rate of ED use for ACSCs among the control group.", "QUESTION": "Does high-Intensity Telemedicine decrease Emergency Department Use for Ambulatory Care Sensitive Conditions by Older Adult Senior Living Community Residents?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "By regulating the expression of its target gene PTEN, which subsequently affects the PI3K/AKT signalling pathway, miR-21 exerts its regulatory role on the radiation sensitivity of K562 cells. These results may help to provide the basis for microRNA-based targeted therapies to overcome radiation resistance in tumour cells.", "QUESTION": "Is microRNA-21 involved in X-ray irradiation resistance in K562 leukaemia cells?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "LAT1 expression is a promising pathological factor for predicting the prognosis in patients with resectable stage I NSCLC.", "QUESTION": "Is l-type amino acid transporter 1 expression a prognostic marker in patients with surgically resected stage I non-small cell lung cancer?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "IR is an independent risk factor of SLI presence and its severity in Koreans. Whether improvement of IR might prevent SLI occurrence needs to be addressed by clinical trials.", "QUESTION": "Does insulin Resistance be a Risk Factor for Silent Lacunar Infarction?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "These results suggest that immune suppression in sepsis may be closely linked to the development of AKI and that sCD25 or IL-10 may be useful as novel biomarkers for the development of septic AKI.", "QUESTION": "Is soluble CD25 increased in patients with sepsis-induced acute kidney injury?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "This study revealed distinct clinical, immunologic, and genetic determinants of early and late wheezing after RSV LRTI, indicating distinct pathophysiological mechanisms. We conclude that late wheezing at age 6 years, but not early postbronchiolitis wheezing, is an asthmatic phenomenon and genetically related to a functional IL-13 polymorphism.", "QUESTION": "Does iL-13 genetic polymorphism identify children with late wheezing after respiratory syncytial virus infection?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Our results suggest that endotoxin may induce a reduction of Caa3 redox status independently of Do2 and Vo2.", "QUESTION": "Does escherichia coli endotoxin reduce cytochrome aa3 redox status in pig skeletal muscle?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "PCT induced the release of proinflammatory cytokines from THP-1 cells and PBMCs. The function of PCT was prevented by the presence of IVIG.", "QUESTION": "Does intravenous immunoglobulin prevent release of proinflammatory cytokines in human monocytic cells stimulated with procalcitonin?" }

{ "CONTEXT": "We have showed that secretory Apolipoprotein J/Clusterin (sCLU) is down-regulated in senescent, stressed or diseased red blood cells (RBCs). It was hypothesized that sCLU loss relates to RBCs vesiculation, a mechanism that removes erythrocyte membrane patches containing defective or potentially harmful components. To investigate this issue we employed a combination of biochemical and microscopical approaches in freshly prepared RBCs or RBCs stored under standard blood bank conditions, an in vitro model system of cellular aging. We found that sCLU is effectively exocytosed in vivo during membrane vesiculation of freshly prepared RBCs. In support, the RBCs' sCLU content was progressively reduced during RBCs ex vivo maturation and senescence under cold storage due to its selective exocytosis in membrane vesicles. A range of typical vesicular components, also involved in RBCs senescence, like Band 3, CD59, hemoglobin and carbonylated membrane proteins were found to physically interact with sCLU.", "LONG_ANSWER": "The maturation of RBCs is associated with a progressive loss of sCLU. We propose that sCLU is functionally involved in the disposal of oxidized/defected material through RBCs vesiculation. This process most probably takes place through sCLU interaction with RBCs membrane proteins that are implicit vesicular components. Therefore, sCLU represents a pro-survival factor acting for the postponement of the untimely clearance of RBCs.", "QUESTION": "Is apolipoprotein J/clusterin in human erythrocytes involved in the molecular process of defected material disposal during vesiculation?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Our results suggested that shear stress alteration could influence the endothelial cell function as well as internal elastic lamella and elastic lamellae remodeling. Low shear stress decreased the permeability of internal elastic lamella and elastic lamellae by reducing fenestrae of them, which involved the enhanced fibronectin expression. Therefore, the increased accumulation of macromolecules in the arterial wall was observed. Our data supply new evidence on the mechanisms of atherogenesis induced by low shear stress.", "QUESTION": "Does flow shear stress affect macromolecular accumulation through modulation of internal elastic lamina fenestrae?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "We have shown that hUCBSC treatments inhibit phosphorylation of EGFR, FAK and c-Src forms. Our findings associate EGFR expression and its localization to mitochondria with specific biological functions in GBM cells and provide relevant preclinical information that can be used for the development of effective hUCBSC-based therapies.", "QUESTION": "Do cord blood stem cells inhibit epidermal growth factor receptor translocation to mitochondria in glioblastoma?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Within intermittent HIV-1 shedders, decreases in FOXP3 T cells at the shedding visit suggests that local HIV-1 replication leads to CD4 T-cell depletion, with increases in the proportion of CD8FOXP3 cells. HIV-1-infected cell loss may promote a cytokine milieu that maintains cellular homeostasis and increases immune suppressor cells in response to HIV-1 replication in the cervical tissues.", "QUESTION": "Is hIV-1 shedding from the female genital tract associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study.", "QUESTION": "Are all APAPs Equivalent for the Treatment of Sleep Disordered Breathing : A Bench Evaluation of Eleven Commercially Available Devices?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Vitamin C improves FDD in patients with CHF as the result of increased availability of nitric oxide. This observation supports the concept that endothelial dysfunction in patients with CHF is, at least in part, due to accelerated degradation of nitric oxide by radicals.", "QUESTION": "Does vitamin C improve endothelial function of conduit arteries in patients with chronic heart failure?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The ER stress response plays an important role in DUE-induced apoptosis in human colon cancer cells.", "QUESTION": "Does dictyopteris undulata Extract induce Apoptosis via Induction of Endoplasmic Reticulum Stress in Human Colon Cancer Cells?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "MA lowered circulating adiponectin through inhibition of adiponectin gene transcription in adipocytes.", "QUESTION": "Does metabolic acidosis lower circulating adiponectin through inhibition of adiponectin gene transcription?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Conditional survival estimates are more optimistic and realistic for cancer survivors than traditional survival estimates over time. For node-positive melanoma survivors, 5-year conditional DFS and DSS improve significantly over time. These estimates are critical to treatment decisions and non-treatment-related planning for both clinicians and patients.", "QUESTION": "Does conditional survival estimate improve over 5 years for melanoma survivors with node-positive disease?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Chronic transplant glomerulopathy is a consequence of chronic active immune-mediated injury. Interstitial fibrosis and tubular atrophy may be associated with T-bet-positive mononuclear cell infiltration in the peritubular region. The T-bet infiltration should be evaluated in patients with chronic allograft injury.", "QUESTION": "Is t-bet-positive mononuclear cell infiltration associated with transplant glomerulopathy and interstitial fibrosis and tubular atrophy in renal allograft recipients?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Propofol infusion, compared with isoflurane inhalation, attenuates ROS production and limits it for 20 minutes after resuming 2LV from OLV. Propofol infusion may be beneficial to patients with inadequate antioxidant capacity.", "QUESTION": "Does propofol infusion shorten and attenuates oxidative stress during one lung ventilation?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer. Response rate is not affected.", "QUESTION": "Does lenograstim prevent morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Niacin treatment was associated with significant increases in HDL apoA-I concentrations and production, as well as enhanced clearance of TRL apoB-100 and apoB-48.", "QUESTION": "Does extended-release niacin alter the metabolism of plasma apolipoprotein ( Apo ) A-I and ApoB-containing lipoproteins?" }

{ "CONTEXT": "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 = 1,015) 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).", "LONG_ANSWER": "The model including the age-specific AMH percentiles as the covariate and using proportional odds as its covariate metrics meets all the statistical criteria for the best model and provides the most clinically relevant and realistic predictions for age at menopause for reproductive-aged women.", "QUESTION": "Are flexible parametric survival models built on age-specific antimüllerian hormone percentiles better predictors of menopause?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The double MBB protocol better correlated with favorable MBN outcomes compared with a single MBB protocol. Using a double MBB protocol, a 70% cutoff value for reported subjective pain relief post-MBB best predicted overall outcome following MBN. Without a confirmatory MBB, an 80% cutoff value was the optimal value.", "QUESTION": "Does correlation of lumbar medial branch neurotomy result with diagnostic medial branch block cutoff values to optimize therapeutic outcome?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "The gradual release of P-R8 from P-R8-DOX/PGA may improve the therapeutic efficacy of water-soluble based nanomedicines for the treatment of solid lung tumors.", "QUESTION": "Does complexation of cell-penetrating peptide-polymer conjugates with polyanions control cells uptake of HPMA copolymers and anti-tumor activity?" }

{ "CONTEXT": "Interleukin-1 (IL-1) is an alleged important cytokine in osteoarthritis (OA), although the exact contribution of IL-1 to joint destruction remains unclear. Here we investigated the involvement of IL-1α and IL-1β in joint pathology during collagenase-induced OA (CiOA). CiOA was induced in wild type (WT) and IL-1αβ Synovial IL-1β expression was strongly elevated 7 days after induction of CiOA in WT mice but decreased afterwards, whereas S100A8/A9, previously described to aggravate OA, remained elevated for 21 days. Remarkably, synovial inflammation was comparable between WT and IL-1αβ", "LONG_ANSWER": "IL-1α and IL-1β are not involved in synovial inflammation and cartilage destruction during CiOA, implicating that other mediators are responsible for the joint damage.", "QUESTION": "Is interleukin-1 involved in synovial inflammation and cartilage destruction in collagenase-induced osteoarthritis?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. Our findings support a role of HFE mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis C.", "QUESTION": "Are common heterozygous hemochromatosis gene mutations risk factors for inflammation and fibrosis in chronic hepatitis C?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Adults consuming more dietary protein from either plant or animal sources had lower long-term risks of HBP.", "QUESTION": "Do diets higher in protein predict lower high blood pressure risk in Framingham Offspring Study adults?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "PPC prevents the alcohol-induced oxidative stress but only in the absence of iron overload.", "QUESTION": "Does polyenylphosphatidylcholine protect against alcohol but not iron-induced oxidative stress in the liver?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Brief, early MMP inhibition after MI yields preservation of LV structure and global as well as scar area passive function, supporting the concept that preserving the original ECM early after coronary occlusion lessens ventricular remodeling.", "QUESTION": "Does early short-term treatment with doxycycline modulate postinfarction left ventricular remodeling?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "FhSPECT is a feasible technology that allows the accurate identification of SLNs in oral cancer. FhSPECT overcomes the shine-through phenomenon, one of the most important limitations of SLNB, thereby confirming the importance of SLNB in patients with cN0 oral cancer.", "QUESTION": "Does intraoperative 3-D imaging improve sentinel lymph node biopsy in oral cancer?" }

{ "CONTEXT": "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).", "LONG_ANSWER": "Verrucous papilloma and mainly verrucokeratotic lesions are strongly associated with the risk of SCC in organ transplant patients, whereas the most typical types of warts: verrucae vulgares and flat warts, are not.", "QUESTION": "Are squamous cell carcinomas associated with verrucokeratotic cutaneous lesions but not with common warts in organ-transplant patients . A case-control study?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Intrapartum assessment of amniotic fluid volume, by amniotic fluid index or the two-diameter pocket technique, is a poor predictor of adverse neonatal outcome.", "QUESTION": "Are intrapartum amniotic fluid index and two-diameter pocket poor predictors of adverse neonatal outcome?" }

{ "CONTEXT": "In this study, we confirmed a protective effect of 15d-PGJ2 in concanavalin A (ConA)-induced fulminant hepatitis in mice and investigated the potential mechanism. Balb/C mice were injected with ConA (25mg/kg) to induce acute fulminant hepatitis, and 15d-PGJ2 (2.5-10μg) was administered 30min after the ConA injection. The histological grade, pro-inflammatory cytokine and ROS levels, apoptosis and autophagy activity, the expression of HO-1, Nrf2, JNK and Bcl-2 activity were determined 2, 4, and 8h after the ConA injection. Following ConA challenge, the expression of cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) was up-regulated. Treatment with 15d-PGJ2 reduced the pathological effects of ConA-induced fulminant hepatitis and significantly reduced the levels of TNF-α, IL-1β and ROS after injection. 15d-PGJ2 inhibited apoptosis and autophagic cell death, facilitated Nrf2 nuclear translocation, increased HO-1 expression and suppressed the JNK activation.", "LONG_ANSWER": "15d-PGJ2 alleviates ConA-induced acute liver injury in mice by up-regulating the anti-oxidative stress factor HO-1 and reducing the production of cytokines and ROS, thereby inhibiting hepatic cell autophagy probably induced by ROS.", "QUESTION": "Does 15d-PGJ2 alleviate ConA-induced acute liver injury in mice by up-regulating HO-1 and reducing hepatic cell autophagy?" }

{ "CONTEXT": "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 μg/L, or rIGF-1 at concentrations of 100, 300 and 500 μg/L for 4 h. 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.", "LONG_ANSWER": "That neither hormone was capable of attenuating levels of oxidative stress mediated via either complex I linked respiration or lipid-derived respiration could have serious health implications for the use of rhGH in healthy individuals, which is frequently associated with significant increases in the bioavailability of free fatty acids (FFA). Such elevated supplies of lipid-derived substrates to the mitochondria could lead to oxidative damage which would negatively impact mitochondrial function.", "QUESTION": "Do recombinant human growth hormone and insulin-like growth factor-1 affect mitochondrial derived highly reactive oxygen species production in peripheral blood mononuclear cells under conditions of substrate saturation in-vitro?" }

{ "CONTEXT": "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.", "LONG_ANSWER": "Treatment with 70 and 200 mg intravenous erythromycin are equally effective in accelerating gastric emptying in the critically ill.", "QUESTION": "Does erythromycin dose of 70 mg accelerate gastric emptying as effectively as 200 mg in the critically ill?" }