Zobrazení zdroje stránky Schaefersmart1015

We have previously demonstrated functional and molecular changes in hippocampal subfields in individuals with schizophrenia (SZ) psychosis associated with hippocampal excitability. In this study, we use RNA-seq and assess global transcriptome changes in the hippocampal subfields, DG, CA3, and CA1 from individuals with SZ psychosis and controls to elucidate subfield-relevant molecular changes. We also examine changes in gene expression due to antipsychotic medication in the hippocampal subfields from our SZ ON- and OFF-antipsychotic medication cohort. We identify unique subfield-specific molecular profiles in schizophrenia postmortem samples compared with controls, implicating astrocytes in DG, immune mechanisms in CA3, and synaptic scaling in CA1. We show a unique pattern of subfield-specific effects by antipsychotic medication on gene expression levels with scant overlap of genes differentially expressed by SZ disease effect versus medication effect. These hippocampal subfield changes serve to confirm and extend our previous model of SZ and can explain the lack of full efficacy of conventional antipsychotic medication on SZ symptomatology. With future characterization using single-cell studies, the identified distinct molecular profiles of the DG, CA3, and CA1 in SZ psychosis may serve to identify further potential hippocampal-based therapeutic targets.The objective was to describe funding sources and publication trends for the primary literature on Peyronie's disease (PD), including direct industry research support. A search of EMBASE, PubMed, Scopus, and Web of Science was performed to identify articles published from 2006 to 2018. Articles not published in English, reviews, case reports, editorials, guidelines, and meta-analysis were excluded from analysis. Data collected included year and journal of publication, major focus, and funding sources. The US Federal Open Payments database was searched for direct industry research payments to authors. Four hundred thirty-seven articles met criteria. The median number of yearly publications was 31. The most frequent publications were Journal of Sexual Medicine (25.6%), Urology (8.9%), BJU International (7.3%), and Journal of Urology (5.7%). Plaque excision/grafting was the most common topic (16.5%) followed by pathophysiology (15.3%), and intralesional therapy (14.9%). Only 15.1% (n = 66) of articles had a funding source with only 2.3% (n = 10) articles receiving any National Institutes of Health (NIH) funding. In total, 4.1% (n = 18) of the articles were industry funded, 61.1% (n = 11) of these from Xiaflex manufacturer Endo/Auxilium. Remaining articles appeared self-funded. There were 1524 unique authors and just 13 received any direct industry funds, totaling US$718,426. Most PD research is self-funded with only a small percentage from NIH or industry.Reconstructive surgery of the penis holds many unique challenges due to the unique physiological properties of the tissues. Much of the effort involved therefore goes to preserving as much of the native tissue as possible whilst novel and creative methods have been adopted to repair defects and in creation of neophallus. A search of the PubMed database was carried out using the following keywords 'penile trauma', 'penile cancer', 'lichen sclerosus', 'glansectomy', 'glans resurfacing', 'penile-sparing surgery', 'micropenis', 'aphallia', 'female-to-male sex reassignment surgery', 'scrotal flap' and 'genital lymphoedema'. Results for glans resurfacing in treating cancer showed low local recurrence rates at 0-10% whilst 90% of lichen sclerosus patients reported complete resolutions of pain and pruritis. For repairs of penile shaft skin defects the literature supports the use of full-thickness skin graft and pedicled scrotal flaps. The radial artery-based forearm free flap remains the best option for neophallus creation in terms of function, sensation and cosmesis but unfortunately leaves a disfiguring scar and involves multiple stages. Some novel techniques have been developed to circumvent these issues and are discussed. This article presents an update on the important developments in the field of penile reconstructive surgery.Peyronie's disease (PD)-related penile deformity is managed with multiple treatment modalities including oral medications, intralesional injections, and surgery. Penile traction therapy (PTT) is one such modality with purported benefits, albeit with notable differences in the characteristics of available traction devices and published study protocols. We provide a comprehensive review of the available data supporting PTT for PD treatment. We performed a rigorous database search to identify all studies pertaining to PTT for the treatment of PD through November 2019. Seventeen trials explored use of PTT as monotherapy or in combination with surgical or nonsurgical treatment, using over five different commercially available devices. All devices were well tolerated, although compliance and daily duration of use were highly variable. PTT resulted in variable improvements in stretched penile length and penile curvature, depending on study protocol, patient population, and device. PTT appears to be a safe and well-tolerated treatment for PD as monotherapy or in combination with other nonsurgical and surgical treatments, and for men in both the acute and chronic phases. Further studies are needed to compare available devices, evaluate device characteristics associated with treatment success, differentiate outcomes in acute vs. chronic PD populations, and determine the optimal duration of use.Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.The treatment of acute myeloid leukemia (AML) is adjusted according to cytogenetic risk factors and molecular markers. Cytarabine remains the main drug to treat AML, and several studies have explored the prognostic relevance of the genotype of cytarabine metabolizing enzymes in AML. Glucuronidation has been identified to be relevant in the cytarabine clearance, but there are still few data concerning the clinical impact of genetic polymorphisms known to condition the activity of UDP-glucuronosyl transferases in AML patients. Here we report the association between the UGT1A1 rs8175347 genotype and the clinical outcome of 455 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. [https://www.selleckchem.com/products/proteinase-k.html https://www.selleckchem.com/products/proteinase-k.html] Patients with the UGT1A1*28 homozygous variant (associated to a lower UGT1A1 activity) had a lower overall survival (OS) (25.8% vs. 45.5%; p 0.004). Multivariate analysis confirmed this association (p 0.008; HR 1.79; 95% CI 1.16-2.76). Subgroup analysis showed the negative effect of the UGT1A1*28 homozygous genotype on OS in women (14.8% vs. 52.7%; p 0.001) but not in men. This lower OS was associated with longer neutropenia after consolidation chemotherapy and with higher mortality without previous relapse, suggesting an association between a low glucuronidation activity and mortal toxic events.PURPOSE Evaluate whether fragile X syndrome (FXS) testing should be transitioned to a second-tier test in global developmental delay, intellectual disability, and autism spectrum disorder in the absence of family history and suggestive clinical features. METHODS Determine the diagnostic yield of FXS testing performed by the Alberta Children's Hospital (ACH) Molecular Diagnostic Laboratory between 2012 and 2017. Retrospective chart review of FXS-positive patients to determine presence or absence of suggestive clinical features and family history. RESULTS Of the 2486 pediatric patients with neurodevelopmental disorders tested for FXS, 25 males and 5 females were positive. This corresponds to a 1.2% diagnostic yield of FXS testing at our center. Retrospective chart review of the FXS-positive cases revealed that 96% of FXS patients had either, if not both, clinical features or family history suggestive of FXS present at the time of testing. Only one patient had neither family history nor clinical features suggestive of FXS. CONCLUSION In 96% of FXS-positive cases, there was sufficient clinical suspicion raised on the basis of clinical features and/or family history to perform targeted FXS testing. We thus propose that in the absence of suggestive clinical features or family history, FXS testing should be transitioned to a second-tier test in neurodevelopmental disorders.The idea that infectious agents in the brain have a role in the pathogenesis of Alzheimer disease (AD) was proposed nearly 30 years ago. However, this theory failed to gain substantial traction and was largely disregarded by the AD research community for many years. Several recent discoveries have reignited interest in the infectious theory of AD, culminating in a debate on the topic at the Alzheimer's Association International Conference (AAIC) in July 2019. In this Viewpoint article, experts who participated in the AAIC debate weigh up the evidence for and against the infectious theory of AD and suggest avenues for future research and drug development.Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation - driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways - contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia-lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.