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Summary from the species of the genus Sphaeromyxa Thélohan, 1892 (Myxosporea: Bivalvulida: Variisporina: Sphaeromyxidae).
OBJECTIVE Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder due to pathogenic mutations in the MECP2 gene. Motor impairment constitutes the core diagnostic feature of RTT. Preclinical studies have consistently demonstrated alteration of excitation/inhibition (E/I) balance and aberrant synaptic plasticity at the cortical level. We aimed to understand neurobiological mechanisms underlying motor deficit by assessing in vivo synaptic plasticity and E/I balance in the primary motor cortex (M1). METHODS In 14 patients with typical RTT, 9 epilepsy control patients, and 11 healthy controls, we applied paired-pulse transcranial magnetic stimulation (TMS) protocols to evaluate the excitation index, a biomarker reflecting the contribution of inhibitory and facilitatory circuits in M1. Intermittent TMS-theta burst stimulation was used to probe long-term potentiation (LTP)-like plasticity in M1. Motor impairment, assessed by ad hoc clinical scales, was correlated with neurophysiological metrics. RESULTS RTT patients displayed a significant increase of the excitation index (p = 0.003), as demonstrated by the reduction of short-interval intracortical inhibition and increase of intracortical facilitation, suggesting a shift toward cortical excitation likely due to GABAergic dysfunction. Impairment of inhibitory circuits was also confirmed by the reduction of long-interval intracortical inhibition (p = 0.002). LTP-like plasticity in M1 was abolished (p = 0.008) and scaled with motor disability (all p = 0.003). INTERPRETATION TMS is a method that can be used to assess cortical motor function in RTT patients. Our findings support the introduction of TMS measures in clinical and research settings to monitor the progression of motor deficit and response to treatment. ANN NEUROL 2020. © 2020 American Neurological Association.A late stage functionalization of the aromatic ring in amino acid derivatives is described. The key step is a copper-catalysed diversification of a boronate ester by amination (Chan-Lam reaction) that can be carried out on a complex β-aryl-β-amino acid scaffold, and not only considerably extends the substrate scope of amination partners, but also delivers an array of potent and selective integrin inhibitors as potential treatments of idiopathic pulmonary fibrosis (IPF). This versatile chemistry strategy, which is amenable to high throughput array protocols, allows the installation of pharmaceutically valuable heteroaromatic fragments at a late stage by direct coupling to the NH heterocycles, leading to compounds with drug-like attributes, and is a useful addition to the medicinal chemist's repertoire. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIM We investigated whether adolescents who had recently disclosed sexual abuse or family violence displayed more psychological trauma symptoms and physical health complaints than unaffected controls. We also investigated to what degree physical health complaints were associated with trauma symptoms in these abuse victims. METHODS Abuse, trauma symptoms and physical health complaints were assessed during face-to-face interviews with 40 sexual abuse victims and 35 family violence victims aged 10-18 years. They had all attended forensic interviews at the Barnehus in Oslo, a specialised Norwegian police unit where evidence is gathered in adolescent-friendly surroundings, from October 2016 to November 2018. Their symptoms were compared with 41 controls from the general population. Linear regression analyses investigated associations between trauma symptoms and physical health complaints. selleck chemicals llc RESULTS Sexually abused adolescents displayed higher levels of post-traumatic stress reactions, depression, dissociation and physical health complaints than unaffected controls. Family violence victims displayed higher levels of post-traumatic stress reactions. Trauma symptoms were associated with physical health complaints and these were most prominent in the adolescents with the highest burden of symptoms. CONCLUSION Based on the high burden of symptoms revealed, clinical examinations of abused adolescents should include a systematic assessment of trauma symptoms and physical health complaints. This article is protected by copyright. selleck chemicals llc All rights reserved.MicroRNAs (miRNAs) provide context-dependent transcriptional regulation of genes comprising signalling networks throughout the developing organism including morphogenesis of the embryonic neural tube (NT). Using a high-sensitivity, high-coverage microarray analysis platform, miRNA expression in the murine embryonic NT during the critical stages of its formation was examined. Analysis of a number of differentially expressed (DE) miRNAs enabled identification of several gene targets associated with cellular processes essential for normal NT development. Using computational pathway analysis, interactive biologic networks and functional relationships connecting DE miRNAs with their targeted messenger RNAs (mRNAs) were identified. Potential mRNA targets and a key signal transduction pathway governing critical cellular processes indispensable for normal mammalian neurulation were also identified. RNA preparations were also used to hybridize both miRNA arrays and mRNA arrays allowing miRNA-mRNA target analysis using data of DE miRNAs and DE mRNAs - co-expressed in the same developing NT tissue samples. Identification of these miRNA targets provides key insight into the epigenetic regulation of NT development as well as into potential mechanistic underpinning of NT defects. SIGNIFICANCE OF THE STUDY This study underscores the premise that microRNAs are potential coordinators of normal neural tube (NT) formation, via regulation of the crucial, planar cell polarity pathway. Any alteration in their expression during neurulation would result in abnormal NT development. © 2020 John Wiley & Sons Ltd.BACKGROUND Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database. METHODS Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios. RESULTS The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.
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