Hansondowling6253

Background & aims Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel-like-factor-6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data is yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid-X-receptor (FXR) signalling. Methods Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analyzed in hepatocyte-specific Klf6-knockout mice following bile duct ligation (BDL). Chromatin-immunoprecipitation-assays (ChIP) and KLF6-overexpressing HepG2 cells were used to analyze the interaction of KLF6 and FXR target genes such as NR0B2. Results Based on IHC, PSC patients could be subdivided into two groups showing either low (80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan-Meier analysis. Klf6-knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region. Conclusion Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2.As of 18 February 2020, the e-cigarette or vaping product use-associated lung injury (EVALI) epidemic has claimed the lives of 68 patients in the USA with the total number of reported cases standing at 2807 to date. We present the clinical and radiologic findings, course of illness, and treatment of EVALI in seven adolescent patients in Northeast Ohio. Five of our patients required supplemental oxygen with four requiring intensive care unit care for respiratory support during admission. Three patients were treated with systemic steroids while inpatient. Bilateral opacities were seen on radiographic imaging of all seven of our patients. All patients were discharged alive on room air. However, impaired diffusing capacity of the lungs for carbon monoxide (DLCO) with nonobstructive spirometry was seen in patients that were tested postdischarge. This suggests that although recovery from the acute illness process of EVALI is achieved, there may be long-term impact on lung function in these patients. We recommend close follow-up with a pediatric pulmonologist where spirometry and DLCO can be performed.Aims We sought to describe the frequency/type/timing of clinical events, and delineate patterns in their transitions, after a first episode of heart failure (HF). SN-011 in vitro Methods and results In 1036 Framingham participants with new-onset HF (mean age 79 years; 53% women), we used mixture models to estimate probabilities of, and time to cardiac death, other-cardiovascular disease (CVD) death, recurrent HF, cardiac events and other-CVD events, accounting for age, sex, HF type (preserved vs. reduced ejection fraction), and prevalent cardiac/CVD events. The most common first events after new-onset HF were cardiac (36%), recurrent HF (28%) and death (29%). Compared with recurrent HF (referent transition state), prevalent cardiac events were associated with higher odds of fatal (odds ratio, OR [95%CI] 1.90 [1.11-3.23]) and non-fatal (2.13 [1.52-3.00]) cardiac events; prevalent CVD increased odds of other-CVD death (1.90 [1.04-3.47]). Among 715 participants without a fatal initial event, there were 3337 distinct epochs (inter-event time-periods), with median 3.0 epochs/participant (49% cardiac [n=1639]; 27% recurrent HF [n=912]). Median inter-event times varied between 12 to 285 days (recurrent HF to other CVD death and non-fatal other CVD, respectively). Prior HF, cardiac and other-CVD events significantly increased odds of developing the same event-type (OR ~5-7-fold), with shortened time to recurrence, indicating "rapid cycling loops" of the same event type. HF type did not impact the nature or timing of future events. Conclusions Comorbidities but not HF type impact clinical course of HF by influencing the type/timing of subsequent events, denoting "natural history loops" within the overall HF population. This article is protected by copyright. All rights reserved.Polymers with sulfur-nitrogen bonds have been underestimated for a long time, although the intrinsic characteristics of these polymers offer a myriad of superior properties (e.g., degradation, flame retardancy, film-forming ability, good solubility in polar solvents, and high refractivity with small chromatic dispersions, among other things) compared to their carbon analogues. The remarkable characteristics of these polymers result from the unique chemical properties of the sulfur-nitrogen bond (e.g., its polar character and the multiple valence states of sulfur), and thus open excellent perspectives for the development of innovative (bio)materials. Accordingly, this review describes the most common chemical approaches toward the efficient synthesis of these ubiquitous polymers possessing diverse sulfur-nitrogen bonds, and furthermore highlights their applications in multiple fields, ranging from biomedicine to energy storage, with the aim of providing an informative perspective on challenges facing the synthesis of sulfur-nitrogen polymers with desirable properties.Objective Community engagement activities are the entry point to a "pipeline" of activity aimed at supporting under-represented students and nurturing their interest in medical careers following graduation. This review aimed to describe the range of activities medical schools undertake to encourage and support rural students or other targeted under-represented populations to apply to medical school, and the reported outcomes. The overarching aim was to identify which programs prior to application into medicine are most effective. Design A systematised review. Setting Medical Education articles published January 2000 to May 2018. Participants Population groups under-represented in medicine, including rural students. Interventions Programs delivered to participants prior to application to medical school. Main outcome measures Reach, format and duration of programs, number of participants applying and completing medical school. Results A search of several databases identified 2688 articles. After filtering for relevance, 1271 articles were considered for the final review.