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62, 95% CI 0.45-0.84, p=0.002) as compared to flexible sigmoidoscopy but not statistically different for CRC (OR 1.15, 95% CI 0.65-2.02, p=0.63).

Despite lower participation amongst patients, CRC screening with flexible sigmoidoscopy leads to higher detection of advanced colorectal neoplasia, when compared to a single round of fecal immunochemical testing.

Despite lower participation amongst patients, CRC screening with flexible sigmoidoscopy leads to higher detection of advanced colorectal neoplasia, when compared to a single round of fecal immunochemical testing.

Functional dyspepsia (FD) symptoms may lead to depression or anxiety in affected individuals and vice versa. These individuals often have more serious somatic symptoms, longer disease recovery time, and tend to consume more medical resources and health care costs. Therefore, recognition of depression and anxiety is crucial to improve clinical outcome in FD patients. The aim of this study is to systematically review the association of functional dyspepsia with depression and anxiety.

This systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A Literature search was carried out with PubMed and ProQuest databases from 1 January 2010 to 5 October 2020. The outcomes of interest were association of functional dyspepsia with depression and anxiety. The quality of each study was assessed using the Joanna Briggs Institute (JBI) tool.

A total of 13 studies involving 14,076 subjects were included in this review. Almost all of the studies nd quality of life of the patients.

In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice.

Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected.

Among 82 patients included in this study (median age 68 years, men 61%), 48 (59%) received chemotherapy. Ac-DEVD-CHO purchase Median overall survival was 4.9 months (0.2-38.7) in the group of patients who did not receive chemotherapy and 12.2 months (1.9-61.0) in chemotherapy group (HR=2.93; 95%CI 1.6-5.3; p<0.0001). In univariate analysis, younger age, male gender, Eastern Cooperative Oncology Group (ECOG) score ≤2, high albumin level, low C-reactive protein level, and endoscopic drainage were significantly associated with introduction of chemotherapy. In multivariate analysis, only ECOG score ≤2 at diagnosis (HR=70.4; 95%CI 4.6-1097.6; p=0.002) and male gender (HR=5; 95%CI 1.5-16.5; p=0.009), were significant independent predictive factors of chemotherapy introduction. Age and bilirubin level at diagnosis were not significant factors in multivariate analysis.

ECOG score ≤ 2 and male gender were the only independent predictive factors of chemotherapy introduction in unresectable biliary tract cancers. Age or initial bilirubin level were not predictors for chemotherapy introduction. These results might help defining the initial therapeutic strategy.

ECOG score ≤ 2 and male gender were the only independent predictive factors of chemotherapy introduction in unresectable biliary tract cancers. Age or initial bilirubin level were not predictors for chemotherapy introduction. These results might help defining the initial therapeutic strategy.Shear stress induced by laminar blood flow has a profound effect on the morphology and functional phenotype of macrovascular endothelial cells. The influence of laminar flow on the glomerular microvascular endothelium, however, remains largely elusive. The glomerular endothelium, including its glycocalyx, is a crucial part of the glomerular filtration barrier, which is involved in blood filtration. We therefore investigated the influence of laminar flow-induced shear stress on the glomerular endothelium. Conditionally immortalized mouse glomerular endothelial cells were cultured for 7 days under a laminar flow of 5 dyn/cm2 to mimic the glomerular blood flow. The cells were subsequently analysed for changes in morphology, expression of shear stress-responsive genes, nitric oxide production, glycocalyx composition, expression of anti-oxidant genes and the inflammatory response. Culture under laminar flow resulted in cytoskeletal rearrangement and cell alignment compared to static conditions. Moreover, production of nitric oxide was increased and the expression of the main functional component of the glycocalyx, Heparan Sulfate, was enhanced in response to shear stress. Furthermore, glomerular endothelial cells demonstrated a quiescent phenotype under flow, characterized by a decreased expression of the pro-inflammatory gene ICAM-1 and increased expression of the anti-oxidant enzymes HO-1 and NQO1. Upon exposure to the inflammatory stimulus TNFα, however, glomerular endothelial cells cultured under laminar flow showed an enhanced inflammatory response. In conclusion, laminar flow extensively affects the morphology and functional phenotype of glomerular endothelial cells in culture. Furthermore, glomerular endothelial cells respond differently to shear stress compared to macrovascular endothelium. To improve the translation of future in vitro studies with glomerular endothelial cells to the in vivo situation, it appears therefore crucial to culture glomerular endothelial cells under physiological flow conditions.During the glyoxylate cycle, isocitrate lyases (ICLs) catalyze the lysis of isocitrate to glyoxylate and succinate. Itaconate has been reported to inhibit an ICL from Mycobacterium tuberculosis (tbICL). To elucidate the molecular mechanism of ICL inhibition, we determined the crystal structure of tbICL in complex with itaconate. Unexpectedly, succinate and itaconate were found to bind to the respective active sites in the dimeric form of tbICL. Our structure revealed the active site architecture as an open form, although the substrate and inhibitor were bound to the active sites. Our findings provide novel insights into the conformation of tbICL upon its binding to a substrate or inhibitor, along with molecular details of the inhibitory mechanism of itaconate.