Yusufrouse4592

The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 million deaths. Early virus-mediated immune suppression is believed to be one of the unique characteristics of SARS-CoV-2 infection and contributes at least partially to the viral pathogenesis. In this study, we identified the key viral interferon antagonists of SARS-CoV-2 and compared them with two well-characterized SARS-CoV interferon antagonists, PLpro and orf6. Here we demonstrated that the SARS-CoV-2 nsp13, nsp14, nsp15 and orf6, but not the unique orf8, could potently suppress primary interferon production and interferon signalling. Although SARS-CoV PLpro has been well-characterized for its potent interferon-antagonizing, deubiquitinase and protease activities, SARS-CoV-2 PLpro, despite sharing high amino acid sequence similarity with SARS-CoV, loses both interferon-antagonising and deubiquitinase activities. Among the 27 viral proteins, SARS-CoV-2 orf6 demonstrated the strongest suppression on both primary interferon production and interferon signalling. Orf6-deleted SARS-CoV-2 may be considered for the development of intranasal live-but-attenuated vaccine against COVID-19.Introduction Recently CDK4/6 inhibitors have been introduced for the treatment of hormone positive breast cancer resistant to endocrine therapy. Among their side effects, alopecia is often reported being associated to patients' distress and depressive symptoms. Case report We report the case of a 70-year-old woman affected by breast cancer in treatment with Palbociclib, who developed alopecia. Management and Outcome We prescribed a topical solution with cetirizine. Global photography, trichoscopy and trichogram were assessed. All evaluations demonstrated alopecia improvement. Discussion Currently, no treatment options for CDK 4/6 inhibitors induced alopecia have been proposed. Herein, we report the use of topical cetirizine.Background Two new drugs, abiraterone and enzalutamide, had recently shown beneficial effects on survival in patients with metastatic castration-resistant prostate cancer. We systematically reviewed the efficacy and safety of abiraterone and enzalutamide in metastatic castration-resistant prostate cancer in real-world practice. Methods A search from PubMed, Web of Science, Cochrane, Embase was conducted up to 6 March 2019. Available articles from conferences were searched. The endpoint was prostate-specific antigen response, overall survival, progression-free survival, number of patients with any adverse event. Results Fourteen cohort studies involving 3469 participants were included. Pooled result showed that prostate-specific antigen response was higher for patients receiving enzalutamide than abiraterone (790 patients, odds ratio (OR) 0.47, 95% confidence interval (CI) 0.29-0.77, P = 0.003, I2=59%). Enzalutamide was significantly associated with increased adverse events rate in comparison with abiraterone (730 patients, OR 0.35, 95%CI 0.13-0.92, P = 0.03, I2=65%). There was no statistical difference between abiraterone and enzalutamide with respect to perceived cognitive impairments (1856 patients, OR 0.90, 95%CI 0.29-2.76, P = 0.85, I2=5%). Enzalutamide was significantly associated with increased fatigue risk in comparison with abiraterone (2477 patients, OR 0.46, 95%CI 0.34-0.63, P＜0.00001, I2=0%). FL118 in vivo Conclusions Our results demonstrated that enzalutamide was more efficacious than abiraterone for patients with metastatic castration-resistant prostate cancer, but was associated with a significantly elevated risk of side effects, particularly fatigue.Rationale Identifying genetic markers for heterogeneous complex diseases such as heart failure is challenging, and requires prohibitively large cohort sizes in genome-wide association studies (GWAS) in order to meet the stringent threshold of genome-wide statistical significance. On the other hand, chromatin quantitative trait loci (QTL), elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritising sub-threshold variants for disease-association. Objective Here, we captured non-coding genetic variants by performing epigenetic profiling for enhancer H3K27ac ChIP-seq in 70 human control and end-stage failing hearts. Methods and Results We have mapped a comprehensive catalogue of 47,321 putative human heart enhancers and promoters. 3,897 differential acetylation peaks (FDR 5%) pointed to pathways altered in heart failure (HF). To identify cardiac histone acetylation QTLs (haQTLs), we regressed out confounding factors including HF disease status, and employed the G-SCI test1 to call out 1,680 haQTLs (FDR 10%). RNA-seq performed on the same heart samples proved a subset of haQTLs to have significant association also to gene expression (expression QTLs), either in cis (180), or through long range interactions (81), identified by Hi-C and HiChIP performed on a subset of hearts. Furthermore, a concordant relationship between the gain or disruption of transcription factor (TF) binding motifs, inferred from alternative alleles at the haQTLs, implied a surprising direct association between these specific TF and local histone acetylation in human hearts. Finally, 62 unique loci were identified by colocalisation of haQTLs with the sub-threshold loci of heart-related GWAS datasets. Conclusions Disease and phenotype-association for 62 unique loci are now implicated. These loci may indeed mediated their effect through modification of enhancer H3K27-acetylation enrichment and their corresponding gene expression differences.The influx of 1.5 million Syrians into Lebanon has created an increased demand for health services, which is largely unmet, due to cost, a highly fragmented and privatised system, and crises around legal documentation and refugee status. The aim of this study was to use a constant comparison analysis of qualitative data to explore how Syrian refugees living in Lebanon describe their experiences accessing healthcare (N = 351 individuals within 46 families). Pervasive fear, lack of confidence in the medical system, and high costs all hinder access to healthcare for Syrians in Lebanon. Findings demonstrate the need for attention to the costs and accessibility of care, and for stronger coordination of care within a centrally led comprehensive emergency plan. While we attend to understanding and alleviating the barriers surrounding refugee healthcare, we must also address the underlying cause of health crisis the brutal realities caused by armed conflict.