Hopkinslauritsen8090

Pharmacological treatment should also be optimised, and some patients may benefit from lung volume reduction surgery. Psychological and behavioural factors are important, but are currently poorly understood in the peri-operative period. Considerations of the risk and benefits of delaying surgery to ensure the recommended measures are delivered depends on patient characteristics and the nature and urgency of the planned intervention.Reduced-sodium, added-potassium salt substitutes have favorable effects on blood pressure, but have not been tested in India. The Salt Substitute in India Study (SSiIS) is a double-blinded, randomized-controlled trial designed to investigate the effects of reduced-sodium, added-potassium salt substitution to replace usual cooking salt use and blood pressure (BP) among hypertensive patients in rural India. The primary objective is to assess effects on systolic blood pressure at 3 months. The secondary objectives are to determine effects on diastolic blood pressure, urinary sodium, and potassium levels, and to determine acceptability of the intervention. Eligible individuals received usual salt (100% sodium chloride) or salt substitute (70% sodium chloride and 30% potassium chloride) to replace all salt required for cooking and seasoning in the household. A total of 502 participants aged ≥18 years with a history of hypertension were successfully recruited and randomized in a 11 ratio to intervention or control, between November 2019 and January 2020. Mean blood pressure at baseline was 133.5/83.6 mm Hg and 96% were using one or more blood pressure-lowering medications. The overall mean average 24-hour urinary sodium excretion was 2825 (SD, 1166) mg/L, which corresponds to a urinary salt excretion of 10.4 g/d. Baseline findings suggest sodium intake in this population significantly exceeds World Health Organization recommendations. The SSiIS trial has successfully recruited participants and is well placed to determine whether salt substitution is an effective means of lowering blood pressure for rural Indian patients with hypertension.Microglia, resident myeloid cells of the central nervous system (CNS), act as immune sentinels that contribute to maintenance of physiological homeostasis and respond to any perturbation in CNS. Microglia could be polarized by various stimuli to perform dedicated functions and instigate inflammatory or pro-regenerative responses. Microglia and peripheral macrophages accumulate in glioblastomas (GBMs), malignant brain tumors, but instead of initiating antitumor responses, these cells are polarized to the pro-invasive and immunosuppressive phenotype which persists for a long time and contributes to a "cold" immune microenvironment of GBMs. Molecular mechanisms underlying this long-lasting "microglia memory" are unknown. We hypothesized that this state may rely on epigenetic silencing of inflammation-related genes. In this study, we show that cultured microglia pre-exposed to glioma-conditioned medium (GCM) acquire a "transcriptional memory" and display reduced expression of inflammatory genes after re-stimulation with lipopolysaccharide. Unstimulated microglia have unmethylated DNA and active histone marks at selected gene promoters indicating chromatin accessibility. Adding GCM increases expression and enzymatic activity of histone deacetylases (Hdac), leading to erasure of histone acetylation at tested genes. Later inflammatory genes acquire repressive histone marks (H3K27 trimethylation), which correlates with silencing of their expression. GCM induced genes acquire active histone marks. Hdac inhibitors block GCM-induced changes of histone modifications and restore microglia ability to initiate effective inflammatory responses. Altogether, we show a scenario of distinct histone modifications underlying polarization of microglia by glioma. We demonstrate contribution of epigenetic mechanisms to glioma-induced "transcriptional memory" in microglia resulting in the tumor-supportive phenotype.Parkinson's disease (PD) is a debilitating movement disorder, significantly afflicting the aging population. Efforts to develop an effective treatment have been challenged by the lack of understanding of the pathological mechanisms underlying neurodegeneration. We have shown that Miro1, an outer mitochondrial membrane protein, situates at the intersection of the complex genetic and functional network of PD. Removing Miro1 from the surface of damaged mitochondria is a prerequisite for mitochondrial clearance via mitophagy. Parkinson's proteins PINK1, Parkin, and LRRK2 are the molecular helpers to remove Miro1 from dysfunctional mitochondria destined for mitophagy. We have found a delay in clearing Miro1 and initiating mitophagy in postmortem brains and induced pluripotent stem cell-derived neurons from PD patients harboring mutations in LRRK2, PINK1, or Parkin, or from sporadic PD patients with no known mutations. In addition, we have shown that reducing Miro1 by both genetic and pharmacological approaches can correct this Miro1 phenotype and rescue Parkinson's-relevant phenotypes in human neurons and fly PD models. These results suggest that the Miro1 defect may be a common denominator for PD, and compounds that reduce Miro1 promise a new class of drugs to battle PD. We propose to couple this Miro1 phenotype with Miro1-based drug discovery in future therapeutic studies, which could significantly improve the success of clinical trials. © 2020 International Parkinson and Movement Disorder Society.The use of some anti-hypertensive drugs in the current COVID-19 pandemic has become controversial. This study investigated possible relationships between anti-hypertensive medications use and COVID-19 infection risk in the ambulatory hypertensive population. This is a population-based retrospective cohort study involving 34 936 hypertensive adults >50 years in Tarragona (Southern Catalonia, Spain) who were retrospectively followed through pandemic period (from 01/03/2020 to 30/04/2020). Resatorvid Two data sets including demographic/clinical characteristics (comorbidities and cardiovascular medications use) and laboratory PCR codes for COVID-19 were linked to construct an anonymized research database. Cox regression was used to calculate multivariable hazard ratios (HRs) and estimate the risk of suffering COVID-19 infection. Across study period, 205 PCR-confirmed COVID-19 cases were observed, which means an overall incidence of 586.8 cases per 100 000 persons-period. In multivariable analyses, only age (HR 1.03; 95% CI 1.