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Background Pocket complications are common after cardiac implantable electronic device implantation. We report a rare case of pyoderma gangrenosum (PG) complicating a permanent pacemaker implantation, and the first literature review of 10 published cases. Case summary Five days after pacemaker implantation for heart failure and 21 atrioventricular block, a 93-year-old man had pain in the scar and bleeding on contact. Two days later, he had fever, inflammatory syndrome, and a necrotic 7-cm wound. click here The pacemaker was removed and he was started on antibiotics. Due to a lack of bacterial growth in samples, PG (a rare aseptic, destructive inflammatory cutaneous condition) was suspected, and histology was compatible with this diagnosis. High-dose corticosteroids vastly improved his condition within 1 week, and after 2 months of decreasing-dose corticosteroid therapy, complete healing and normalization of the inflammatory syndrome were observed. link2 Discussion Pyoderma gangrenosum should be considered if there is aseptic skin ulceration that is not controlled by antibiotic treatment. The first-line treatment for PG is high-dose systemic corticosteroids. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin β3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer. © The Author(s) 2020.Catalyzing life-sustaining reactions, proteins are composed by 20 different amino acids that fold into a compact yet flexible three-dimensional architecture, which dictates what their function(s) might be. Determining the spatial arrangement of the atoms, the protein's 3D structure, enables key advances in fundamental and applied research. Protein crystallization is a powerful technique to achieve this. Unlike Earth's crystallization experiments, biomolecular crystallization in space in the absence of gravitational force is actively sought to improve crystal growth techniques. However, the effects of changing gravitational vectors on a protein solution reaching supersaturation remain largely unknown. Here, we have developed a low-cost crystallization cell within a CubeSat payload module to exploit the unique experimental conditions set aboard a sounding rocket. We designed a biaxial gimbal to house the crystallization experiments and take measurements on the protein solution in-flight with a spectrophotometry system. After flight, we used X-ray diffraction analysis to determine that flown protein has a structural rearrangement marked by loss of the protein's water and sodium in a manner that differs from crystals grown on the ground. We finally show that our gimbal payload module design is a portable experimental setup to take laboratory research investigations into exploratory space flights. © The Author(s) 2020.Parkinson's disease (PD) is the second most prevalent neurological disorder and has been the focus of intense investigations to understand its etiology and progression, but it still lacks a cure. Modeling diseases of the central nervous system in vitro with human induced pluripotent stem cells (hiPSC) is still in its infancy but has the potential to expedite the discovery and validation of new treatments. Here, we discuss the interplay between genetic predispositions and midbrain neuronal impairments in people living with PD. We first summarize the prevalence of causal Parkinson's genes and risk factors reported in 74 epidemiological and genomic studies. We then present a meta-analysis of 385 hiPSC-derived neuronal lines from 67 recent independent original research articles, which point towards specific impairments in neurons from Parkinson's patients, within the context of genetic predispositions. Despite the heterogeneous nature of the disease, current iPSC models reveal converging molecular pathways underlying neurodegeneration in a range of familial and sporadic forms of Parkinson's disease. Altogether, consolidating our understanding of robust cellular phenotypes across genetic cohorts of Parkinson's patients may guide future personalized drug screens in preclinical research. © The Author(s) 2020.A new virus termed SARS-COV-2 (causing COVID-19 disease) can exhibit a progressive, fatal impact on individuals. The World Health Organization (WHO) has declared the spread of the virus to be a global pandemic. Currently, there are over 1 million cases and over 100,000 confirmed deaths due to the virus. Hence, prophylactic and therapeutic strategies are promptly needed. In this study we report an epitope, ITLCFTLKR, which is biochemically fit to HLA allelic proteins. We propose that this could be used as a potential vaccine candidate against SARS-COV-2. A selected putative epitope and HLA-allelic complexes show not only better binding scores, but also RMSD values in the range of 0-1 Å. This epitope was found to have a 99.8% structural favorability as per Ramachandran-plot analysis. Similarly, a suitable range of IC50 values and population coverage was obtained to represent greater validation of T-cell epitope analysis. Stability analysis using MDWeb and half-life analysis using the ProtParam tool has confirmed that this epitope is well-selected. This new methodology of epitope-based vaccine prediction is fundamental and fast in application, ad can be economically beneficial and viable. © 2020 Published by Elsevier Ltd.This commentary, on Heine and Quintavalla's article Priorities and Human Rights, considers the authors' position that, while the right to life and other civil and political rights are equally as important as health and other social rights, some degree of prioritizing types of rights is necessary because all rights cannot be implemented simultaneously. This commentary concurs with Heine and Quintavalla's challenge to the common argument that civil and political rights are of higher importance [1-3]. But this commentary goes further, in suggesting that before a society begins to prioritize implementation of human rights, it must first secure the basic understanding that the right to health is indeed equally important to civil and political rights. This commentary uses the example of national courts to show how judicial engagement with the right to health has begun to chip away at the boundary between the categories of rights. It suggests that greater interconnection among health and other rights has also made mapping out a hierarchical relationship far more difficult. Thus, before implementation can have any defined order, states must first come to a shared understanding regarding the equal if not greater importance of the right to health. © 2020 Elsevier Masson SAS. All rights reserved.The year 2019 brought about a multitude of innovations in clinical infectious diseases. With the continued rise of antimicrobial resistance (AMR), advances in diagnostics and newly available antibiotics offer additional strategies for combating this threat, but the broken antibiotic market serves as an impediment to further developments. The IDSA and other stakeholders are working to create novel pull incentives to stabilize the pipeline. Ongoing needs include developing optimal stewardship practices, including by using narrow-spectrum antibiotics and shorter durations of therapy. In the area of solid organ transplantation, early data from transplanting Hepatitis C virus (HCV)-infected organs are encouraging and the American Society of Transplantation (AST) released new guidelines addressing several key issues. Lastly, 2019 saw a resurgence in Measles emphasizing the importance of vaccination. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Type I interferon kappa (IFNκ) is selectively expressed in human keratinocytes. Herpes simplex virus-1 (HSV-1) is a human pathogen that infects keratinocytes and causes lytic skin lesions. Whether IFNκ plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ and poly (IC); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFNκ and poly (IC). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ in NHEK led to significantly enhanced HSV-1 replication in both undifferentiated and differentiated NHEK compared to scrambled siRNA-transfected cells, while the addition of recombinant IFNκ significantly reduced HSV-1 replication in NHEK. In addition, we found that IFNκ did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFNκ is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection. link3 Copyright © 2020 Yuanyuan Li et al.Background Premature ovarian insufficiency (POI) represents the hypergonadotropic hypoestrogenic symptoms that result in the loss of ovarian follicles. 5-30% POI cases are suggested to be involved in autoimmune etiology. MicroRNA-21 (miR-21) plays a vital role in ovarian folliculogenesis via regulating and interacting with multiple target genes. Here, we conduct the target prediction of miR-21, identify the expression and correlation of miR-21 and its putative target Pellino-1 (Peli1), and confirm their relationship with clinical characteristics in autoimmune POI. Methods Bioinformatic analysis was conducted to screen the miR-21 putative target gene. Autoimmune POI mouse models were established by ZP3 immunization. Serum miR-21, Peli1 mRNA of peripheral blood mononuclear cells (PBMCs) and regulatory T cells (Tregs), general status, spleen Tregs ratio, inflammatory factors, ovarian endocrine function, and ovarian structure were evaluated. For autoimmune POI patients, serum miR-21, PBMCs Peli1 mRNA levels, genein autoimmune POI patients, suggesting that miR-21 and Peli1 might be associated with the pathogenesis of autoimmune POI. Copyright © 2020 Xinran Li et al.The aim of this study was to evaluate the effects of flash glucose monitoring on dietary variety, physical activity, and self-care behavior in patients with diabetes. This study included outpatients with diabetes using insulin who presented at the Department of Diabetes and Metabolism of the Ise Red Cross Hospital. Before initiating flash glucose monitoring and 12 weeks after its initiation, blood glucose-related parameters were assessed and self-administered questionnaires were completed (Dietary Variety Score (DVS), the International Physical Activity Questionnaire (IPAQ), the Summary of Diabetes Self-Care Activities Measure (SDSCA), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ)) and compared between the two time points. We analyzed 42 patients with type 1 diabetes mellitus and 48 patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, but not type 1 diabetes mellitus, there was an increase in moderate/high category scores for IPAQ (P less then 0.001) and for treatment satisfaction reported via DTSQ.
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