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A single case of intergenotypic recombinant form (2b/1a) and a single case of mixed infection (1a and 3a) were also identified. Each sequence derived from hemophiliacs was more than 0.05 genetic distance away from the other sequences in phylogenetic analysis. CONCLUSIONS Various HCV genotypes were identified in Japanese hemophiliacs, a finding that reflects the HCV genotypic distribution in the USA. The genetic distance among them are the results of viral evolution in each patient plus HCV genetic diversity in the USA. © 2020 The Japan Society of Hepatology.The 40th Annual David W. Smith Workshop on Malformations and Morphogenesis occurred August 23rd -28th, 2019 at the Snowbird Resort in Snowbird, Utah. The Workshop, which honors the legacy of David W. Smith, brought together clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis from around the world. In addition to mechanisms of morphogenesis and delineation of new syndromes, the Workshop highlighted five themes deformations, disruptions and fetal dysmorphology; orofacial clefting; central nervous system malformations; ciliopathies; and X-linked intellectual disabilities. This Conference Report includes the abstracts presented at the 2019 Workshop. © 2020 Wiley Periodicals, Inc.The human PXR (pregnane X receptor), a master regulator of drug metabolism, has essential roles in intestinal homeostasis and abrogating inflammation. Existing PXR ligands have substantial off-target toxicity. Based on prior work that established microbial (indole) metabolites as PXR ligands, we proposed microbial metabolite mimicry as a novel strategy for drug discovery that allows exploiting previously unexplored parts of chemical space. Here, we report functionalized indole derivatives as first-in-class non-cytotoxic PXR agonists as a proof of concept for microbial metabolite mimicry. The lead compound, FKK6 (Felix Kopp Kortagere 6), binds directly to PXR protein in solution, induces PXR-specific target gene expression in cells, human organoids, and mice. FKK6 significantly represses pro-inflammatory cytokine production cells and abrogates inflammation in mice expressing the human PXR gene. The development of FKK6 demonstrates for the first time that microbial metabolite mimicry is a viable strategy for drug discovery and opens the door to underexploited regions of chemical space. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.BACKGROUND Previous studies have shown that the dysregulation of lncRNAs participates in non-small cell lung cancer (NSCLC) development. The purpose of this study was to research the biological function of lncRNA SNHG14 and its molecular mechanism in NSCLC progression. METHODS RT-PCR was applied for investigating the expression of SNHG14, miR-206 and G6PD. The progression of NSCLC was detected by CCK-8, Transwell and western blot assays. The targets of SNHG14 and miR-206 were measured by dual-luciferase reporter assay. RESULTS We found a higher expression of SNHG14 in NSCLC and upregulation of SNHG14 contributed to NSCLC cell proliferation, invasion and migration. However, knockdown of SNHG14 showed the opposite effect on the progression of NSCLC. Specifically, SNHG14 negatively regulated miR-206 expression by binding with it directly. Furthermore, G6PD served as the target of miR-206. Rescue experiments showed that SNHG14 promoted G6PD expression by inhibiting miR-206. CONCLUSIONS LncRNA SNHG14 contributed to NSCLC progression through miR-206/G6PD axis, providing novel clues for understanding the mechanism of NSCLC. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.AIMS Sacubitril/valsartan (SV) reduced heart failure hospitalization and cardiovascular mortality compared with enalapril in the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure trial. However, this trial excluded patients with end stage of renal disease (ESRD); thus, the efficacy and safety of SV in heart failure with reduced ejection fraction (HFrEF) with ESRD remains uncertain. METHODS AND RESULTS We retrospectively analysed the clinical and laboratory data of 501 HFrEF patients who administered with SV from March 2017 to April 2019 in a single tertiary university hospital. A total of 23 HFrEF patients with ESRD on dialysis [58.3% non-ischaemic heart failure; left ventricular ejection fraction (LVEF) 29.7 ± 4.4%] were included in this study. At baseline and follow-up visit, we evaluated cardiovascular biomarkers such as high-sensitive troponin T (hsTnT), soluble ST2 (sST2), echocardiographic parameters, and clinical and adverse events. The meashould be warranted. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.Even when they no longer require the presence of iron, cells use zinc as a divalent cation, involved in a large variety of catalytic and regulatory functions. This metal is so important that it appears that ribosomes are instrumental in its ultimate storage. Here, we summarize a detailed analysis which investigates the way the global cell metabolism is integrated by zinc. This integration results from the zinc-dependent way in which the one-carbon metabolism is always coupled to the translation process, not only via methionine and S-adenosylmethionine, but via the complex set-up of the modification of the position 34 of the anticodon of tRNAs. © 2020 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.AIM The associations between types of dietary protein intake and child anthropometric measurements have not been fully studied. Therefore, we examined dietary protein pattern in relation to anthropometric indicators among 6-year-old children. METHODS We carried out a cross-sectional study of 788 randomly selected children from health centres in Tehran, Iran. Dietary intake was assessed using a food frequency questionnaire completed by the mothers. Anthropometric measurements were based on standard protocols. Principle component analysis was performed to identify different dietary protein patterns. We used multivariate logistic regression to evaluate how these patterns were associated with child anthropometry. RESULTS Three dietary protein patterns were identified pattern 1 (rich in red and processed meats, dairy products and eggs), pattern 2 (rich in fish and poultry) and pattern 3 (rich in soy and legumes). After adjusting for potential confounders (energy intake, socioeconomic status and physical activity), being in the third compared to the first tertiles of pattern 2 was associated with increased (OR = 1.57; 95% CI 1.09-2.27; P = .01) and decreased (OR = 0.54; 95% CI 0.32-0.92; P = .02) risk of overweight/obesity and underweight/wasting, respectively. There was no association between other dietary patterns and risk of overweight/obesity or underweight/wasting. CONCLUSIONS The present study showed inverse association between the fish/white meat pattern and underweight/wasting and also a positive association between higher fish/white meat protein intake and higher risk of overweight/obesity. Further studies are needed to confirm these results. © 2020 Dietitians Association of Australia.INTRODUCTION Pre-exposure prophylaxis (PrEP) is a key HIV prevention technology, and is a pillar of a comprehensive HIV prevention approach for men who have sex with men (MSM). Because there have been no national data to characterize trends in the PrEP continuum in the United States, overall and for key demographic groups of MSM, we aimed to describe the extent to which PrEP awareness, willingness and use changed over time, overall and for specific groups of MSM critical for HIV prevention (e.g. Black and Hispanic MSM, younger MSM, MSM in rural areas and MSM without health coverage). METHODS The American Men's Internet Survey (AMIS) is an annual survey of US MSM conducted in the United States among MSM aged ≥15 years since 2013. We analysed data on trends in elements of the PrEP continuum (awareness, willingness and use of PrEP) in a sample of 37,476 HIV-negative/unknown status MSM from December 2013 through November 2017. We evaluated trends in continuum steps overall and among demographic subgroups using Po epidemic control or health equity. © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.OBJECTIVE To chart patient-reported outcome measures (PROMs) in Norwegian patients treated for definite neuroborreliosis (NB). MATERIAL AND METHODS Adult patients treated for definite NB 1-10 years earlier supplied demographics, symptoms and treatment during NB, and answered validated questionnaires; Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), health-related quality of life questionnaire (RAND-36), and Patient Health Questionnaire (PHQ-15). RESULTS A higher proportion of NB-treated persons reported severe fatigue, defined as FSS score ≥ 5, than in Norwegian normative data, but when removing persons with confounding fatigue associated comorbidities (n = 69) from the analyses, there was no difference between groups. Physical health-related quality of life (RAND-36 PCS), mean FSS score, proportions of persons reporting moderate or severe somatic symptom burden (PHQ-15 score ≥ 10), anxiety (HADS-A ≥ 8), or depression (HADS-D ≥ 8) did not differ between NB-treated persons and reference scores. Mental health-related quality of life (RAND-36 MCS) was poorer than in normative data (47.1 vs. 53.3), but associated with anxiety, depression and current moderate or severe somatic symptom burden, and not with NB characteristics. CONCLUSIONS Results on validated PROM questionnaires measuring fatigue, anxiety, depression, self-reported somatic symptom burden, and physical health-related quality did not differ between persons treated for definite NB 1-10 years earlier and reference scores. NB-treated persons tended to report a slightly poorer mental health-related quality of life than found in normative data, but when adjusting for confounders the causative connection is questionable. Overall, the long-term prognosis of definite NB seems to be good. © 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.INTRODUCTION Heterogeneity of sociodemographics and risk behaviours across the HIV treatment cascade could influence the public health impact of universal ART in sub-Saharan Africa if those not virologically suppressed are more likely to be part of a risk group contributing to onward infections. Sociodemographic and risk heterogeneity across the treatment cascade has not yet been comprehensively described or quantified and we seek to systematically review and synthesize research on this topic among adults in Africa. METHODS We conducted a systematic review of peer-reviewed literature in Embase and MEDLINE databases as well as grey literature sources published in English between 2014 and 2018. AMG 487 order We included studies that included people living with HIV (PLHIV) aged ≥15 years, and reported a 90-90-90 outcome awareness of HIV-positive status, ART use among those diagnosed or viral suppression among those on ART. We summarized measures of association between sociodemographics, within each outcome, and as a composite measure of population-wide viral suppression.

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