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Detection and Portrayal of Individual Observational Scientific studies in Healthy Epidemiology upon Gut Microbiomics regarding Combined Data Analysis.
We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal-based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1-6 cells. Five NPs (Ag, CuO, ZnO, SiO2 , and V2 O5 ) exhibit cytotoxicity in both cell types, while SiO2 and V2 O5 induce IL-1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO2 in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL-1β release, and cleavage of gasdermin-D. This releases pore-performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V2 O5 induces IL-1β release and delays caspase 1 activation by vanadium ion interference in membrane Na+ /K+ adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1-6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal-based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.A 35-year-old woman experienced chronic antibody-mediated rejection (cAMR) after her first and second liver transplantations. After the second transplant with cAMR, belatacept was started, with normalization of her liver function. Two years later, she became pregnant. She was continued on belatacept together with low doses of slow-release tacrolimus, azathioprine, and steroids. Her pregnancy was uneventful and her child healthy, with none of the frequent complications seen in pregnancies during immunosuppression. Although belatacept is not yet approved by the US Food and Drug Administration in liver transplantation, its role in specific liver transplant recipients should be considered. This article is protected by copyright. All rights reserved.BACKGROUND Spinal muscular atrophy (SMA) is an inherited neuromuscular disease affecting 1 in 8,000 newborns. The majority of patients carry bi-allelic variants in the survival of motor neuron 1 gene (SMN1). SMN1 is located in a duplicated region on chromosome 5q13 that contains Alu elements and is predisposed to genomic rearrangements. Due to the genomic complexity of the SMN region and genetic heterogeneity, approximately 50% of SMA patients remain without genetic diagnosis that is a prerequisite for genetic treatments. In this work we describe the diagnostic odyssey of one SMA patient in whom routine diagnostics identified only a maternal heterozygous SMN1Δ(7-8) deletion. METHODS We characterized SMN transcripts, assessed SMN protein content in peripheral blood mononuclear cells (PBMC), estimated SMN genes dosage, and mapped genomic rearrangement in the SMN region. RESULTS We identified an Alu-mediated deletion encompassing exons 2a-5 of SMN1 on the paternal allele and a complete deletion of SMN1 on the maternal allele as the cause of SMA in this patient. CONCLUSION Alu-mediated rearrangements in SMN1 can escape routine diagnostic testing. Parallel analysis of SMN gene dosage, SMN transcripts, and total SMN protein levels in PBMC can identify genomic rearrangements and should be considered in genetically undefined SMA cases. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.BACKGROUND Due to extensive clinical and genetic heterogeneity of intellectual disability (ID) syndromes, the process of diagnosis is very challenging even for expert clinicians. Despite recent advancements in molecular diagnostics methodologies, a significant fraction of ID patients remains without a clinical diagnosis. METHODS, RESULTS, AND CONCLUSIONS Here, in a prospective study on a cohort of 21 families (trios) with a child presenting with ID of unknown etiology, we executed phenotype-driven bioinformatic analysis method, PhenIX, utilizing targeted next-generation sequencing (NGS) data and Human Phenotype Ontology (HPO)-encoded phenotype data. This approach resulted in clinical diagnosis for eight individuals presenting with atypical manifestations of Rubinstein-Taybi syndrome 2 (MIM 613684), Spastic Paraplegia 50 (MIM 612936), Wiedemann-Steiner syndrome (MIM 605130), Cornelia de Lange syndrome 2 (MIM 300590), Cerebral creatine deficiency syndrome 1 (MIM 300352), Glass Syndrome (MIM 612313), Mental retardation, autosomal dominant 31 (MIM 616158), and Bosch-Boonstra-Schaaf optic atrophy syndrome (MIM 615722). © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, LLC.AIM Positive symptoms are a critical dimension of psychopathology in psychotic disorders and are used as a criterion for diagnosis across the psychosis continuum. Although initially considered as one dimension, there is evidence for multidimensionality within positive symptoms. The positive symptom structure has not been examined in individuals at clinical high risk (CHR) for psychosis. Knowledge of the dimensional structure of positive symptoms within CHR may contribute to our understanding of the aetiology and trajectory of this key facet of psychosis. METHOD Exploratory factor analysis (EFA) was conducted on the Prodromal Questionnaire-Brief for 183 individuals meeting CHR criteria. Internal consistency was examined to determine the hierarchical structure of the data and alternative models were compared. RESULTS EFA revealed a three factor model, grouping in to perceptual abnormalities, grandiose/unusual delusions and persecutory/thought delusions, with a general factor accounting for 56% of the variance. Confirmatory factor analysis showed that a hierarchical model was the best fit. One item referring to nihilistic thoughts did not load on any factor. CONCLUSION There is a clear three-dimensional model, distinguishing perceptual abnormalities, and two subgroups of delusions in CHR individuals. The factors are similar to those found in psychotic disorders. The identification and comparison of symptomatic models is useful given the prominent role positive symptoms play in diagnosis, and is crucial to our understanding of the clinical progression of psychosis. This work may provide a useful tool for future studies examining correlations with varying symptom factors and disease progression in CHR. cAMP agonist © 2020 John Wiley & Sons Australia, Ltd.The EU's research policies have always been more about political goals than science. The EU Green Deal may again fail to address the real problems. © 2020 The Author.OBJECTIVE This study aimed to delineate the causal relationship between Ménière's disease and depression. DESIGN Two longitudinal follow-up studies MAIN OUTCOME MEASURES The 2002-2013 Korean National Health Insurance Service-Health Screening Cohort was used. In study I, Ménière's disease patients were 14 matched with the control I group for age group, sex, income group, and region of residence, and the occurrence of depression was observed. In study II, the depression patients were 14 matched with the control II group for the same variables, and the occurrence of Ménière's disease was observed. The stratified Cox proportional hazard model was used. Subgroup analyses were performed according to age and sex. RESULTS In study I, 6.9% (420/6,044) of the Ménière's disease patients and 3.7% (885/24,176) of the control I participants experienced depression. The adjusted hazard ratio (HR) of Ménière's disease for depression was 1.94 (95% confidence intervals [CI] = 1.73-2.18, P less then 0.001). In study II, 1.6% (490/ 31,649) of the depression patients and 1.0% (1,240/126,596) of the control II participants were diagnosed with Ménière's disease. The adjusted HR of depression for Ménière's disease was 1.58 (95% CI = 1.43-1.76, P less then 0.001). All age and sex subgroups demonstrated higher HRs of Ménière's disease for depression (study I) and depression for Ménière's disease (study II). CONCLUSION Ménière's disease patients showed an increased likelihood of depression. Conversely, depression patients showed an elevated likelihood of Ménière's disease. This article is protected by copyright. All rights reserved.After traumatic events, children with different types of attentional biases produce different psychological reactions with the help of the rumination process. A sample of 909 middle school students was taken from the Yunnan Ludian earthquake-affected area. Measurement scales of the Chinese version of the Attention to Positive and Negative Information Scale (APNI), the Chinese version of the Children's Revised Impact of Event Scale (CRIES), and the Revised Post-traumatic Growth Inventory for Children (PTG-C) were used to assess the attentional bias, risk of post-traumatic stress disorder (PTSD), and post-traumatic growth (PTG), respectively. The effect of self-reported attention bias was explored by using a structural equation model and bias-corrected bootstrap test on children's psychological reaction after trauma. The results show that there is a positive relationship between self-reported negative attentional bias and PTSD symptoms partially mediated by intrusive rumination and the negative relationship between self-reported positive attentional bias and PTSD symptoms.
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