Riverapost1251

The frequencies of the variant allele were 1.29%-5.50%. The genes were MTOR, TSC2, IRS1, RAB6B, RALA, HTR6, and ZNF337. PDSVs in IRS1, RAB6B, ZNF337, RALA, and HTR6 had not been previously associated with FCD. In one lesion, two PDSVs were found in two genes. In a transfected cell line, we demonstrated that the c.1791dupG (identified in FCDII from Patient 1) led to a truncated IRS1 and significant mTOR hyperactivation compared to cells that carried wild-type IRS1. mTOR was also activated in FCDII tissue from Patient 1. SIGNIFICANCE Seven PDSVs were identified in FCDII lesions in six of 17 children. Five variant genes had not been previously associated with cortical malformations. We demonstrated that the IRS1 variant led to mTOR hyperactivation in vitro. Although functional experiments are needed, the results provide evidence for novel candidate genes in the pathogenesis of FCDII. Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report a novel ortho-selective C-H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using R f I and R f Br as commercially available reagents. The availability and price of the starting materials as well as the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, e.g. for bio-active compounds and materials. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIMS The aim of this systematic review was to identify generic instruments for drug discontinuation in patients with polypharmacy in the primary care setting. METHODS We systematically searched PubMed and EMBASE, 8 guideline databases (AWMF, NICE, NGC, SIGN, NHMRC, CPG, KCE), the Cochrane Library and grey literature (Google) in 2016 and 2017. Two independent researchers screened and analysed data. The drug discontinuation instruments of the included publications were described and classified. RESULTS We identified 16 relevant publications. Here we found complex algorithms as well as instruments composed of distinct sequential steps. Two guidelines are constructed as electronic web-applications. Instruments revealed diverging emphases on the stages of deprescribing, i.e. preparation, drug evaluation, decision-making and implementation. Accordingly, 3 types of instruments emerged general frameworks, detailed drug assessment tools and comprehensive discontinuation guidelines. CONCLUSION Diverse generic instruments exist for different areas of applications in regard to drug discontinuation. However, there is still a need for practical and user-friendly tools that support physicians in communicational aspects, visualise trade-offs and also enhance patient involvement. © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.Autosomal recessive spastic paraplegia 52 is caused by biallelic mutations in AP4S1 which encodes a subunit of the adaptor protein complex 4 (AP-4). Using next-generation sequencing, we identified three novel unrelated SPG52 patients from a cohort of patients with cerebral palsy. The discovered variants in AP4S1 lead to reduced AP-4 complex formation in patient-derived fibroblasts. To further understand the role of AP4S1 in neuronal development and homeostasis, we engineered the first zebrafish model of AP-4 deficiency using morpholino-mediated knockdown of ap4s1. In this model, we discovered several phenotypes mimicking SPG52, including altered CNS development, locomotor deficits, and abnormal neuronal excitability. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.Self-assembled metallosupramolecular architectures (MSAs) with built-in functionalities such as light-harvesting metal centers are a promising approach for developing emergent properties within discrete molecular systems. Herein we describe the synthesis of two new but simple "click" ligands featuring a bidentate 2-pyridyl-1,2,3-triazole chelate pocket linked to a monodentate pyridyl (either 3- or 4-substituted, L1 and L2) units. The ligands and the corresponding four Pd 2+ and Pt 2+ metallo-ligands (Pd1, Pd2, Pt1 and Pt2) were synthesized and were characterized by nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and X-ray crystallography. Solid-state characterization of the series of ligands and metallo-ligands revealed that these compounds adopt a co-planar conformation of all the aryl units. The Pt 2+ containing metallo-ligands (Pt1 and Pt2) were found to assemble into square (Sqr) and triangular (Tri) shaped architectures when combined with neutral PdCl 2 linker units. Additionally, the ability of the Pt 2+ metallo-ligands and Tri to photocatalyze the cycloaddition of singlet oxygen to anthracene was investigated. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.We encountered a 64-year-old man with hyperosmolar hyperglycemic syndrome, having a sudden-onset homonymous right inferior quadrantanopia. This is the first documentation of such a phenomenon in hyperosmolar hyperglycemic syndrome. We believe this is a variant of hemianopia in patients with hyperglycemic hyperosmolar syndrome. © 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.This study describes the clinical characteristics of the African swine fever (ASF) outbreaks in 14 domestic pig farms in the Republic of Korea. ASF outbreak was identified by farmers' notifications in 11 farms and by active surveillance in the remaining three. At the time of notification, farmers reported sudden death, abortion, and anorexia in sows. Death was the primary symptom identified by farmers in fattener pigs. The number of animals exhibiting clinical symptoms did not exceed four heads at notification, and the number of asymptomatic virus positives was four heads per farm on average. As ASF virus was detected only in the same pig house (in a pen for fattener pigs) in each of 14 ASF outbreak farms, there has been no evidence of house-to-house viral spread within any of the ASF outbreak farms. PF-04620110 nmr This in turn supports our hypothesis that infection was successfully detected during its initial phase. This article is protected by copyright. All rights reserved.