Notes

Derivation associated with human pluripotent come mobile or portable range by way of CRISPR/Cas9 mediated removal regarding exon Three LAMA2 gene (DMBi001-A-1).
Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17-specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL "licenses" IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis.Background Despite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. DMH1 Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19. Method and analysis We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 Prospero registration number CRD42020177953.Objective To examine the association between triglycerides and cholesterol serum values and risk of developing heart failure in women. Design Longitudinal observational study of four cohorts 50-year-old women examined in 1968-1969, 1980-1981, 1992-1993 and 2004-2005, and followed until 2012. S-triglycerides and s-cholesterol were measured at baseline and heart failure morbidity and mortality data collected from 1980 to 2012. Setting Prospective population study Gothenburg, Sweden. Primary care. Participants 1143 women 50 year old without history of heart failure or myocardial infarction. Main outcome measure Association among s-triglycerides, s-cholesterol and heart failure expressed as HR for heart failure, adjusted for smoking, body mass index (BMI), physical activity and age. link2 Results For 50-year-old women examined in 1968-1969, there was an independent association between level of s-triglycerides and heart failure and a significantly higher risk of developing heart failure (HR 1.8; CI 1.16 to 2.80, for each increment of 1.0 mmol/L in s-triglycerides), adjusted for smoking, BMI, physical activity and age. There was no significant association between s-cholesterol and risk of heart failure (HR 0.9; CI 0.77 to 1.15). In the cohorts of 50-year-old women examined in 1980 and 1992, there were no significant associations between neither s-triglycerides or s-cholesterol and the risk of heart failure. In the pooled analyses of the cohorts examined in 1968, 1980 and 1992, a significantly increased risk of heart failure was found (HR 1.49; CI 1.10 to 2.03) for s-triglycerides independently, but not for s-cholesterol. None of the 50-year-old women examined in 2004-2005 developed heart failure by 2012 and were excluded from further analyses. Conclusions High levels of s-triglycerides but not s-cholesterol may be a risk marker for later development of heart failure in 50-year-old women.Introduction We developed a zero-dimensional (0D) model to assess the patient-specific haemodynamics in the circle of Willis (CoW). Similar numerical models for simulating the cerebral blood flow (CBF) had only been validated qualitatively in healthy volunteers by magnetic resonance (MR) angiography and transcranial Doppler (TCD). This study aims to validate whether a numerical model can simulate patient-specific blood flow in the CoW under pathological conditions. Methods and analysis This study is a diagnostic accuracy study. We aim to collect data from a previously performed prospective study that involved patients with aneurysmal subarachnoid haemorrhage (aSAH) receiving both TCD and brain Computerd Tomography angiography (CTA) at the same day. The cerebral flow velocities are calculated by the 0D model, based on the vessel diameters measured on the CTA of each patient. In this study, TCD is considered the gold standard for measuring flow velocity in the CoW. The agreement will be analysed using Pearson correlation coefficients. Ethics and dissemination This study protocol has been approved by the Medical Ethics Review Board of the University Medical Center Groningen METc2019/103. The results will be submitted to an international scientific journal for peer-reviewed publication. Trial registration number NL8114.Objectives Mental healthcare is commonly aimed at reducing symptoms in individual service users. When only symptomatic recovery is addressed, not all service users experience sufficient recovery, and when care is aimed only at individuals (instead of the neighbourhood), not all people in need of mental healthcare are reached. This study evaluated a project that aimed to improve mental healthcare in a neighbourhood, by improving healthcare providers' outreach to the residents living in the neighbourhood, by improving collaboration among healthcare providers and focussing on the residents' personal recovery. This project was carried out by several public health services. It aimed to change the goal of mental healthcare provided in the neighbourhood from symptom reduction to personal recovery. Design The study included qualitative focus groups and inductive content analysis. Setting Primary and secondary mental healthcare that healthcare workers from different healthcare services provided. Participants The evaluation was conducted through three focus group interviews with services users, their friends and relatives, neighbourhood residents, neighbourhood representatives and the healthcare services that were involved (n = 24). Results Evaluation indicated that the most valued part of the project was the utilisation of peer workers at the initiation of mental healthcare. Improved communication among healthcare providers that the project fostered was also highly regarded. The aim of the project to align it with existing initiatives in the neighbourhood was also considered important, although it was difficult to achieve. Conclusions The project did not find a panacea for recovery-oriented community mental healthcare. A variety of its components did, however, contribute to the mental health of the community residents.Introduction Recent evidence has implicated the precuneus of the medial parietal lobe as one of the first brain areas to show pathological changes in Alzheimer's disease (AD). Damage to the precuneus through focal brain injury is associated with impaired visually guided reaching, particularly for objects in peripheral vision. This raises the hypothesis that peripheral misreaching may be detectable in patients with prodromal AD. The aim of this study is to assess the frequency and severity of peripheral misreaching in patients with mild cognitive impairment (MCI) and AD. Methods and analysis Patients presenting with amnestic MCI, mild-to-moderate AD and healthy older-adult controls will be tested (target N=24 per group). link3 Peripheral misreaching will be assessed using two set-ups a tablet-based task of lateral reaching and motion-tracked radial reaching (in depth). There are two versions of each task, one where participants can look directly at targets (free reaching), another wheren they must maintain central fixation (peripheral reaching). All tasks will be conducted first on their dominant, and then their non-dominant side. For each combination of task and side, a Peripheral Misreaching Index (PMI) will be calculated as the increase in absolute reaching error between free and peripheral reaching. Each patient will be classified as showing peripheral misreaching if their PMI is significantly abnormal, by comparison to control performance, on either side of space. We will then test whether the frequency of peripheral misreaching exceeds the chance level in each patient group and compare the overall severity of misreaching between groups. Ethics and dissemination Ethical approval was provided by the National Health Service (NHS) East of England, Cambridge Central Research Ethics Committee (REC 19/EE/0170). The results of this study will be published in a peer-reviewed journal and presented at academic conferences.Objectives Lung cancer CT screening can reduce lung cancer mortality, but high false-positive rates may cause adverse psychosocial consequences. The aim was to analyse the psychosocial consequences of false-positive lung cancer CT screening using the lung cancer screening-specific questionnaire, Consequences of Screening in Lung Cancer (COS-LC). Design and setting This study was a matched cohort study, nested in the randomised Danish Lung Cancer Screening Trial (DLCST). Participants Our study included all 130 participants in the DLCST with positive CT results in screening rounds 2-5, who had completed the COS-LC questionnaire. Participants were split into a true-positive and a false-positive group and were then matched 12 with a control group (n=248) on sex, age (±3 years) and the time of screening for the positive CT groups or clinic visit for the control group. The true positives and false positives were also matched 12 with participants with negative CT screening results (n=252). Primary outcomes Primary outcomes were psychosocial consequences measured at five time points. Results False positives experienced significantly more negative psychosocial consequences in seven outcomes at 1 week and in three outcomes at 1 month compared with the control group and the true-negative group (mean ∆ score >0 and p0 and p less then 0.004) compared with the true-negative group and the control group. No long-term psychosocial consequences were identified either in false positives or true positives. Conclusions Receiving a false-positive result in lung cancer screening was associated with negative short-term psychosocial consequences. These findings contribute to the evidence on harms of screening and should be taken into account when considering implementation of lung cancer screening programmes. Trial registration number NCT00496977.
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