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T cell lineage decisions are critical for the development of proper immune responses to pathogens as well as important for the resolution of inflammatory responses. This differentiation process relies on a combination of intrinsic and extrinsic factors converging upon epigenetic regulation of transcriptional networks relevant to specific T cell lineages. As these biochemical modifications represent therapeutic opportunities in cancer biology and autoimmunity, implications of writers and readers of epigenetic marks to immune cell differentiation and function are highly relevant. Given the ready adoption of histone methyltransferase inhibitors in the clinic, we focus this review on the role of three histone modifying complexes: PRC-1, PRC-2, and G9A in modulating T cell fate decisions. Furthermore, we explore the role of long non-coding RNAs in regulating these processes, and discuss recent advances and challenges of implementing epigenetic therapies into clinical practice.

AIMTo characterize isolated non-obstructive sinusoidal dilatation (SD) by identifying associated conditions, laboratory findings, and histological patterns.METHODSRetrospectively reviewed 491 patients with SD between 1995 and 2015. Patients with obstruction at the level of the small/large hepatic veins, portal veins, or right-sided heart failure were excluded along with history of cirrhosis, hepatic malignancy, liver transplant, or absence of electrocardiogram/cardiac echocardiogram. Liver histology was reviewed for extent of SD, fibrosis, red blood cell extravasation, nodular regenerative hyperplasia, hepatic peliosis, and hepatocellular plate atrophy (HPA).RESULTSWe identified 88 patients with non-obstructive SD. Inflammatory conditions (32%) were the most common cause. The most common pattern of liver abnormalities was cholestatic (76%). Majority (78%) had localized SD to Zone III. Medication-related SD had higher proportion of portal hypertension (53%), ascites (58%), and median AST (113 U/L) and ALT (90 U/L) levels. Nineteen patients in our study died within one-year after diagnosis of SD, majority from complications related to underlying diseases.CONCLUSIONSignificant proportion of SD and HPA exist without impaired hepatic venous outflow. Isolated SD on liver biopsy, in the absence of congestive hepatopathy, requires further evaluation and portal hypertension should be rule out.

Background Gastric cancer (GC) is an important cause of morbidity and mortality worldwide. However, population-based data on GC mortality dynamics in low and middle income countries are scarce. Methods We analyzed GC mortality in Brazil based on all GC-related deaths registered 2000-2015.Results A total of 17,374,134 deaths were recorded, with GC identified in 214,808 (1.24%) cases-203,941 (94.9%) as underlying cause, and 10,867 (5.1%) as associated cause of death. Adjusted rates for age and sex was 6.85 deaths/100,000 inhabitants [95% confidence interval (CI) 6.73-6.97]. The highest mortality rates were found in males [10.00; rate ratio (RR) 1.85; 95% CI 1.78-1.91; p < 0.0001] and patients ≥ 45 years of age (24.98; RR 3.79; 95% CI 3.55-4.05; p < 0.0001). The South (7.56; RR 1.62; 95% CI 1.50-1.76; p < 0.0001) and Southeast (7.36; RR 1.59; 95% CI 1.48-1.71; p < 0.0001) regions had the highest regional rates. Spatial and spatiotemporal high-risk mortality areas in 2004-2007 were located mainly in the South, Southeast, and Central-West regions. After 2008, the Northeast region became a high-risk area, especially Ceará State. Conclusion GC remains a significant public health problem with high mortality burden and unequal distribution in Brazilian states. The new patterns in poorer regions and the high risk in some specific populations show a clear process of epidemiological transition over time. There is a need to strengthen nationwide epidemiological monitoring, surveillance, prevention, and control for GC in the country.

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