Notes

Growing your phenotypic array of Mendelian ligament problems to feature notable kidney phenotypes.
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm with 5-year survival as low as 6%. It is therefore imperative to explore potential treatment avenues to improve survival in these groups of patients. Anti-estrogenic hormone therapy (AEHT) is well-tolerated and has been used in estrogen receptor (ER) subgroups of breast cancer. ER is a type of sex hormone receptor which have been reported to be expressed inconsistently in pancreatic cancer. This study aims to identify the presence of ER in PDAC specimens to guide potential use of AEHT in the management of unresectable PDAC.

This is a retrospective case control study of 10 patients (5 males, 5 females) who underwent pancreatic resections for PDAC from 2011 to 2012. Sections of the post-operative specimens were prepared and sent for ER staining. Pancreatic tissue specimens that were analysed included (I) ductal epithelial cells; (II) acinar cells; (III) islet cells; (IV) intralobular stromal cells; and (V) adenocarcinoma cells.

Intralobular stromal cells were positively stained for ER in 7/10 (70%) of the cases, but were of weak intensity and patchy in distribution. Islet cells (<1%) stained for ER in 3/10 (30%) of the cases. Ductal epithelial cells, acinar cells and adenocarcinoma cells stained negative for ER in all of the cases.

This pilot study did not detect the presence of ER expression in PDAC. ER expression in intralobular stromal and islet cells which was previously unreported, were noted in our study. The role of AEHT in pancreatic cancer remains uncertain and does not appear to be of value at present.
This pilot study did not detect the presence of ER expression in PDAC. ER expression in intralobular stromal and islet cells which was previously unreported, were noted in our study. The role of AEHT in pancreatic cancer remains uncertain and does not appear to be of value at present.
The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired clearance of gut-derived neurotoxins and increased systemic inflammation are thought to play key roles. The diagnosis is based on detection of neurophysiological and neuropsychometric abnormalities. The Psychometric Hepatic Encephalopathy Score (PHES) have been found to correlate with markers of systematic inflammation including interleukin 6, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). This study explores the associations between the PHES score and systemic inflammation, endotoxins and disease severity using baseline data from a trial involving patients with cirrhosis and minimal or no HE (NCT01769040).

Arterial blood was obtained during hepatic vein catheterization, from 54 patients [median age 55 (range, 33-70) years; 83% men] with decompensated but stable cirrhosis. None had clinical evidence of HE but 34 (55.6%) had an abnormal PHES score indicating the presence of minimal HE. Relationships were sought between the PHES score and markers of systemic inflammation, high sensitivity-CRP, cytokines (SDF-1α, TGF-b1, IP-10, IL-6, 10 and 18, and TNF-α; lipopolysaccharide (LPS), the lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14); and the blood ammonia.

No significant relationships were found between the PHES score and any of the variables tested with the single exception of the correlation with serum IL-6 (r=-0.29, 95% confidence interval, -0.53 to -0.02, P=0.031). No independent predictors of the PHES score were identified in regression analyses.

No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.
No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are highly prevalent forms of chronic liver diseases globally, associated with rising all-cause morbidity and mortality. While distinct diseases, NAFLD and ALD share several similarities; both can result in fatty liver disease, steatohepatitis, associated hepatic fibrosis and cirrhosis-related complications, including hepatocellular carcinoma (HCC). Our understanding of the pathophysiology and manifestations of these diseases has advanced significantly, which has established a new foundation to identify therapeutic targets and test new treatments. This review underscores emerging pathogenic pathways that establish a template for target identification and clinical trials. see more Success is critically dependent upon productive interactions between academic investigators and industry to address unmet therapeutic needs in NAFLD and ALD.Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are some of the most common liver diseases worldwide. The human gut microbiome is dynamic and shifts in bacterial composition have been implicated in many diseases. Studies have shown that there is a shift in bacterial overgrowth favoring pro-inflammatory mediators in patients with advanced disease progression such as cirrhosis. Further investigation demonstrated that the transplantation of gut microbiota from advanced liver disease patients can reproduce severe liver inflammation and injury in mice. Various techniques in manipulating the gut microbiota have been attempted including fecal transplantation and probiotics. This review focuses on the changes in the gut microbiota as well as emerging lines of microbiome work with respect to NAFLD and ALD.Inter-individual and inter-ethnic differences and difference in the severity and progression of liver disease among patients with non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) suggests the involvement of genetic and epigenetic factors in their pathogenesis. This article reviews the genetic and epigenetic modifiers in patients with NAFLD and ALD. Evidence regarding the genetic and epigenetic disease modifiers of NAFLD and ALD was reviewed by searching the available literature. Both genome wide association studies (GWAS) and candidate gene studies pertaining to the pathogenesis in both diseases were included. Clinical implications of the available information are also discussed. Several studies have shown association of both NAFLD and ALD with I148M PNPLA3 variant. In addition to the higher prevalence of hepatic steatosis, the I148M PNPLA3 variant is also associated with severity of liver disease and risk of hepatocellular carcinoma (HCC). TM6SF2 is the other genetic variant shown to be significantly associated with hepatic steatosis and cirrhosis in patients with NAFLD and ALD.
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