KGaA, Weinheim.Short telomere syndromes are a heterogenous spectrum of disorders leading to premature cellular aging. These may involve bone marrow failure, adult-onset idiopathic pulmonary fibrosis, and liver disease, and classical entities such as dyskeratosis congenita. We report a patient who presented with common variable immunodeficiency at 3 years of age and autoimmune cytopenias at 8 years of age. He was found to have short telomeres, and genetic testing confirmed a hemizygous mutation NM_001363.4 c.-142C > G in DKC1 gene. He subsequently developed cirrhosis with severe portal hypertension and hepatopulmonary syndrome, prompting liver transplantation at 11 years of age. He remains well 10 years after transplant with no progression of bone marrow failure or progressive lung disease. In conclusion, short telomere syndromes should be considered as a potential cause of pediatric liver disease of unknown etiology, and in severe cases, isolated liver transplantation may be both appropriate and successful. © 2020 Wiley Periodicals, Inc.BACKGROUND For better application in human forensic cases and population genetics research, it is imperative to investigate the genetic characteristics of Guanzhong Han population using enhanced Y-chromosomal short tandem repeats (Y-STR) detecting system with higher discriminating power than previous ones. METHODS In this study, 38 Y-STRs were profiled in 430 unrelated Chinese Han male individuals from Guanzhong region of Shaanxi Province, Northwest China, using the Yfiler™ Platinum PCR Amplification Kit. Haplotype frequencies and forensic parameters were calculated. Comprehensive population comparisons with geographically/ethnically different populations in China and other worldwide countries were performed. RESULTS A total of 422 different haplotypes were observed with the overall haplotype diversity (HD), discriminatory power (DC) and haplotype match probability (HMP) were 0.9999, 0.9814, and 0.0024, respectively. Guanzhong Han showed genetically affinity with Han ethnicity from Shanxi and Henan provinces, while far distant from Tibetan populations. CONCLUSION This study offered a unique insight into Guanzhong Han population, the 38 Y-STRs included in the the Yfiler™ Platinum system are highly polymorphic and informative and can be used for forensic practice and human genetic research. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.The replacement of carbon with nitrogen can affect the aromaticity of organic rings. Nucleus-independent chemical shift (NICS) calculations at the center of the aromatic π-systems reveal that incorporating nitrogen into 5-membered heteroaromatic dienes has only a small influence on aromaticity. In contrast, each nitrogen incorporated into benzene results in a sequential and substantial loss of aromaticity. The contrasting effects of nitrogen-substitution in 5-membered dienes and benzene are reflected in their Diels-Alder reactivities as dienes. 1,2-Diazine experiences a 1011-fold increase in reactivity upon nitrogen-substitution at the 4- and 5-positions, whereas a 5-membered heteroaromatic diene, furan, experiences a comparatively incidental 102-fold increase in reactivity upon nitrogen-substitution at the 3- and 4-positions. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty-five adults aged 55 to 85 were recruited and divided into three groups control (apnea-hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract-Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free-water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p  less then  .05 corrected) and lower FW fraction (p  less then  .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p  less then  .05 corrected). No between-group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.In vitro studies have indicated that the P2Y12 receptor antagonist selatogrel is a substrate of organic-anion-transporting-polypeptide (OATP)1B1 and OATP1B3 that are known to mediate hepatic uptake. Selatogrel is primarily eliminated via the biliary route. Therefore, the study aim was to investigate the effect of rifampin-mediated OATP1B1 and OATP1B3 inhibition on the pharmacokinetics (PK) of selatogrel. This was a randomized, double-blind, placebo-controlled, two-period, cross-over study in 14 healthy subjects. In each period, a single subcutaneous dose of 4 mg selatogrel was administered, either immediately after a single intravenous 30 min infusion of 600 mg rifampin or after placebo. Plasma samples were collected for 36 h and analyzed using a validated LC-MS/MS method.  https://www.selleckchem.com/products/fht-1015.html  PK parameters of selatogrel were calculated using non-compartmental analysis. The effect of rifampin was explored based on geometric mean Cmax and AUC0-∞ ratios and for tmax by Wilcoxon signed rank test. In addition, the safety and tolerability of the study treatments were evaluated. The geometric mean ratios of Cmax and AUC0-∞ were 1.19 (90% CI 1.11, 1.28) and 1.43 (90% CI 1.36, 1.51), respectively, indicating a minor selatogrel exposure increase when administered after an infusion of rifampin compared to placebo. Rifampin administration did not affect t½ or tmax of selatogrel. All study treatments were safe and well tolerated. A single dose of 600 mg rifampin, a potent OATP1B1/1B3 inhibitor, did not impact the PK of selatogrel to a clinically relevant extent suggesting that OATP1B1 and OATP1B3 transporters do not play a major role in the elimination of selatogrel. This article is protected by copyright. All rights reserved.