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Transfusion-acquired Hemoglobinopathies: A study associated with 2 Circumstances.
Ultrastructural examination identified typical coronavirus particles characterized by spike structure in cytoplasm of hepatocytes in two COVID-19 cases. SARS-CoV-2 infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation, and glycogen granule decrease. Histologically, massive hepatic apoptosis and a certain binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scanty CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. Conclusions SARS-CoV-2 infection in liver is a crucial cause of hepatic impairment in COVID-19 patients. Hence, a surveillance of viral clearance in liver and long outcome of COVID-19 is required.Background Gallbladder cancer (GBC) has a female predominance, although other biliary tract cancers (BTCs) such as extrahepatic and intrahepatic bile duct (EHBDC and IHBDC) and ampulla of Vater (AVC) have a male predominance. The role of female reproductive factors in BTC etiology remains unclear. Methods We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results During 21,681,798 person-years of follow-up, 875 GBC, 379 IHBDC, 450 EHBDC, and 261 AVC cases occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72, 95% CI 1.25, 2.38). Age at menarche (HR per year increase 1.15, 95% CI 1.06, 1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13, 95% CI 1.04, 1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19, 95% CI 1.09, 1.31) and EHBDC HR 1.11, 95% CI 1.01, 1.22) in Asian women only. Conclusion We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest sex hormones may have distinct effects on cancers across the biliary tract and vary by geography.There is increasing interest in clinical prediction models in psychiatry, which focus on developing multivariate algorithms to guide personalized diagnostic or management decisions. The main target of these models is the prediction of treatment response to different antidepressant therapies. This is because the ability to predict response based on patients' personal data may allow clinicians to make improved treatment decisions, and to provide more efficacious or more tolerable medications to the right patient. PLB-1001 We searched the literature for systematic reviews about treatment prediction in the context of existing treatment modalities for adult unipolar depression, until July 2019. Treatment effect is defined broadly to include efficacy, safety, tolerability and acceptability outcomes. We first focused on the identification of individual predictor variables that might predict treatment response, and second, we considered multivariate clinical prediction models. Our meta-review included a total of 10 systematic reviews; seven (from 2014 to 2018) focusing on individual predictor variables and three focusing on clinical prediction models. These identified a number of sociodemographic, phenomenological, clinical, neuroimaging, remote monitoring, genetic and serum marker variables as possible predictor variables for treatment response, alongside statistical and machine-learning approaches to clinical prediction model development. Effect sizes for individual predictor variables were generally small and clinical prediction models had generally not been validated in external populations. There is a need for rigorous model validation in large external data-sets to prove the clinical utility of models. We also discuss potential future avenues in the field of personalized psychiatry, particularly the combination of multiple sources of data and the emerging field of artificial intelligence and digital mental health to identify new individual predictor variables.Alcohol use disorder has multiple characteristics including excessive ethanol consumption, impaired control over drinking behaviors, craving and withdrawal symptoms, compulsive seeking behaviors, and is considered a chronic condition. Relapse is common. Determining the neurobiological targets of ethanol and the adaptations induced by chronic ethanol exposure is critical to understanding the clinical manifestation of alcohol use disorders, the mechanisms underlying the various features of the disorder, and for informing medication development. In the present review, we discuss ethanol's interactions with a variety of neurotransmitter systems, summarizing findings from preclinical and translational studies to highlight recent progress in the field. We then describe animal models of ethanol self-administration, emphasizing the value, limitations, and validity of commonly used models. Lastly, we summarize the behavioral changes induced by chronic ethanol self-administration, with an emphasis on cue-elicited behavior, the role of ethanol-related memories, and the emergence of habitual ethanol seeking behavior.Pathological remodeling of the extracellular matrix (ECM) by activated myofibroblasts is a hallmark of fibrotic diseases and desmoplastic tumors. Activation of myofibroblasts occurs in response to fibrogenic tissue injury as well as in tumor-associated fibrotic reactions. The molecular determinants of myofibroblast activation in fibrosis and tumor stroma have traditionally been viewed to include biochemical agents, such as dysregulated growth factor and cytokine signaling, which profoundly alter the biology of fibroblasts, ultimately leading to overexuberant matrix deposition and fibrosis. More recently, compelling evidence has shown that altered mechanical properties of the ECM such as matrix stiffness are major drivers of tissue fibrogenesis by promoting mechano-activation of fibroblasts. In this Review, we discuss new insights into the role of the biophysical microenvironment in the amplified activation of fibrogenic myofibroblasts during the development and progression of fibrotic diseases and desmoplastic tumors.
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