Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

实习护生情绪智力、临床实习环境与病人安全感知能力的中介效应

目的:了解实习护生情绪智力、临床实习环境与病人安全感知能力现状并探讨三者关系。方法:采用情绪智力量表、临床实习环境量表和卫生职业教育病人安全感知量表对492名实习护生进行调查。结果:实习护生情绪智力总分为(123.81±18.69)分,临床实习环境总分为(119.48±22.16)分,病人安全感知能力总分为(67.16±12.06)分,情绪智力、临床实习环境与病人安全感知能力呈正相关(r值分别为0.723和0.720,P<0.01);情绪智力在临床实习环境和病人安全感知能力间起部分中介效应,中介效应估计值为0.286(28.6%)。结论:学校要举办人文课程活动以培养情绪智力;医院应制订计划增加学习机会,选拔给予护生充分支持的带教老师,改善临床实习环境。     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

Acute care nurses’ attitudes toward nursing students with disabilities: A focused ethnography

Discrimination towards individuals with disabilities is problematic within nursing. There have been calls to increase diversity in nursing and this includes embracing nurses with disabilities. Increasing diversity in nursing requires increasing diversity among nursing students; in this way, nurse educators are gatekeepers to the profession. Clinical education is a crucial element of nursing education, yet there have been very few studies related to the clinical education of nursing students with disabilities. There have been no studies of attitudes of acute care nurse preceptors toward students with disabilities in the United States. This gap is important as the majority of clinical experiences occur in the acute care environment. Utilizing a focused ethnography, semi-structured interviews were conducted with 20 acute care nurses with at least two years’ experience precepting students. While positive feelings about nursing students with disabilities were shared, thoughts and behavioral intentions remained negative. Six themes emerged: safety, barriers, otherness, communicating to meet needs, disclosure, and student versus colleague. Attitudinal barriers are the primary barriers faced by individuals with disabilities in becoming and practicing as nurses. Nurses in practice and education must embrace more inclusive attitudes towards individuals with disabilities.     

发达国家医学生器官捐献意愿研究现状的范围综述

目的了解发达国家医学生器官捐献意愿研究的目的、结果、障碍因素和解决对策。 方法以主题词和自由词联合的方式对PubMed、Web of Science、Ovid MEDLINE、Ovid EMBASE(Excerpta Medica)、EBSCOhost Complete和Cochrane Library等已发表文献数据库，以及灰色文献数据库York Centre for Reviews and Dissemination、Open Grey、ProQuest Dissertation and Theses和Mednar进行系统、全面地检索，并采用Arksey和O′Malley提出的范围综述框架进行文献资料整合。 结果共纳入17项发达国家医学生器官捐献意愿研究。研究背景主要为医学生未来对于公众器官捐献有着重要影响。研究结果表明，大多数医学生器官捐献意愿性良好，但不同亚组的研究结果不一；其最主要的障碍因素为医学生器官捐献相关知识的缺乏；解决对策主要为施予系统化、结构化和可评价的教育课程。 结论21世纪以来发达国家医学生器官捐献意愿研究方兴未艾，其研究的多层面、多角度以及揭示的问题、寻求的解决对策，可对我国现阶段医学生器官捐献的研究提供一定参考。     

原发性干燥综合征生物标志物的研究进展

目前原发性干燥综合征(pSS)诊断仍然依赖于侵入性小涎腺活检手术,常导致其早期诊断异常艰难,因此筛选特定生物标志物可能对pSS诊断和个体化治疗极为有益。本文回顾传统标志物及与B细胞活化和表观遗传相关的新标志物,并综述组学标志物研究进展。尽管生物标志物前景较好,但其可靠性仍需扩大样本量进行验证。     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.