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Research has been conducted on Mycobacterium tuberculosis ahpC gene. The role of this gene in M. tuberculosis biology and in resistance to the reactive nitrogen species and survival in macrophages has been investigated and the details are reported.

Discusses advantages and limitations of database software in meeting the educational objectives of history instruction; reviews five currently available computer programs (FACTFILE, QUEST, QUARRY BANK 1851, Census Analysis, and Beta Base); highlights major considerations that arise in designing such programs; and describes their classroom use. (MBR)

Introduction: Studies on the impacts of COVID-19 on patient safety are emerging. However, few studies have elicited the perspectives of front-line clinicians., Methods: We interviewed clinicians from 16 US hospitals who worked in the emergency department, intensive care unit or inpatient unit during the COVID-19 pandemic. We asked about their experiences with both clinician well-being and patient care throughout the pandemic. We used a rigorous thematic analysis to code the interview transcripts. This study was part of a larger randomised control trial of an intervention to improve healthcare worker well-being during the COVID-19 pandemic; the findings described here draw from clinicians who spontaneously raised issues related to patient safety., Results: 11 physicians and 16 nurses in our sample raised issues related to patient safety. We identified two primary themes: (1) compromised access to healthcare and (2) impaired care delivery. First, clinicians discussed how changes in access to healthcare early in the pandemic-including a shift to telehealth and deferred care-led to delays in accurate diagnosis and patients presenting later in their disease course. Second, clinicians discussed the effects of COVID-19 on care delivery related to staffing, equipment shortages and space constraints and how they deviated from the standard of care to manage these constraints. Clinicians noted how these issues led to patient safety events such as central line infections, patient falls and serious medication administration errors., Conclusions: Several well-intentioned interventions implemented in the early weeks of the pandemic created a unique context that affected patient safety throughout the pandemic. Future pandemic preparedness should consider planning that incorporates a patient safety lens to mitigate further harm from occurring during a public health crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the well-being supports provided to health care workers (HCWs) during the COVID-19 pandemic in health centers and hospitals., Design: Cross-sectional qualitative interviews before and after implementation of a peer-based support intervention., Setting: Purposively sampled hospitals and health centers across the US., Participants: 28 site leaders and 56 HCWs sampled from 16 hospitals and 12 health centers., Method: Site leaders and HCWs were asked to describe supports available to HCWs during the COVID-19 pandemic. Thematic and content coding and analysis of interview responses were conducted using Dedoose., Results: Both site leaders and HCWs identified a range of support resources available. Communication resources were the most frequently cited in both groups. Health care workers reported bi-directional communication, while one-way communication was emphasized by site leaders. Hospitals highlighted counseling support, particularly Employee Assistance Programs (EAP), while health centers prioritized community support. Wellness activities were more prevalent in hospital settings, while health centers offered specific workplace-provided training for HCWs. Health care workers encountered barriers when accessing support, including limited time, fear of stigma, and disruptions to their existing support networks attributable to the pandemic., Conclusion: While there are resources for HCWs, the available supports may not align with their needs and barriers to access may limit the effectiveness of these supports. Continued engagement between leaders and HCWs could help better align resources with needs., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Stress First Aid is an evidence-informed peer-to-peer support intervention to mitigate the effect of the COVID-19 pandemic on the well-being of health care workers (HCWs)., Objective: To evaluate the effectiveness of a tailored peer-to-peer support intervention compared with usual care to support HCWs' well-being at hospitals and federally qualified health centers (FQHCs) during the COVID-19 pandemic., Design, Setting, and Participants: This cluster randomized clinical trial comprised 3 cohorts of HCWs who were enrolled from March 2021 through July 2022 at 28 hospitals and FQHCs in the US. Participating sites were matched as pairs by type, size, and COVID-19 burden and then randomized to the intervention arm or usual care arm (any programs already in place to support HCW well-being). The HCWs were surveyed before and after peer-to-peer support intervention implementation. Intention-to-treat (ITT) analysis was used to evaluate the intervention's effect on outcomes, including general psychological distress and posttraumatic stress disorder (PTSD)., Intervention: The peer-to-peer support intervention was delivered to HCWs by site champions who received training and subsequently trained the HCWs at their site. Recipients of the intervention were taught to respond to their own and their peers' stress reactions., Main Outcomes and Measures: Primary outcomes were general psychological distress and PTSD. General psychological distress was measured with the Kessler 6 instrument, and PTSD was measured with the PTSD Checklist., Results: A total of 28 hospitals and FQHCs with 2077 HCWs participated. Both preintervention and postintervention surveys were completed by 2077 HCWs, for an overall response rate of 28% (41% at FQHCs and 26% at hospitals). A total of 862 individuals (696 females [80.7%]) were from sites that were randomly assigned to the intervention arm; the baseline mean (SD) psychological distress score was 5.86 (5.70) and the baseline mean (SD) PTSD score was 16.11 (16.07). A total of 1215 individuals (947 females [78.2%]) were from sites assigned to the usual care arm; the baseline mean (SD) psychological distress score was 5.98 (5.62) and the baseline mean (SD) PTSD score was 16.40 (16.43). Adherence to the intervention was 70% for FQHCs and 32% for hospitals. The ITT analyses revealed no overall treatment effect for psychological distress score (0.238 [95% CI, -0.310 to 0.785] points) or PTSD symptom score (0.189 [95% CI, -1.068 to 1.446] points). Post hoc analyses examined the heterogeneity of treatment effect by age group with consistent age effects observed across primary outcomes (psychological distress and PTSD). Among HCWs in FQHCs, there were significant and clinically meaningful treatment effects for HCWs 30 years or younger: a more than 4-point reduction for psychological distress (-4.552 [95% CI, -8.067 to -1.037]) and a nearly 7-point reduction for PTSD symptom scores (-6.771 [95% CI, -13.224 to -0.318])., Conclusions and Relevance: This trial found that this peer-to-peer support intervention did not improve well-being outcomes for HCWs overall but had a protective effect against general psychological distress and PTSD in HCWs aged 30 years or younger in FQHCs, which had higher intervention adherence. Incorporating this peer-to-peer support intervention into medical training, with ongoing support over time, may yield beneficial results in both standard care and during public health crises., Trial Registration: ClinicalTrials.gov Identifier: NCT04723576.

Background: The COVID-19 pandemic created unprecedented conditions for clinicians providing end-of-life care in acute care settings, yet almost 2 years since the start of the pandemic, little is known about its impact on clinicians., Objectives: To qualitatively explore how clinicians experienced their role as they cared for dying patients with COVID-19 during the pandemic and the impact of these experiences on their lives as health care professionals., Methods: In-depth, hour-long interviews were conducted by phone in the spring of 2022 at a single time point with 23 physicians and nurses in critical care and emergency department settings from 2 health systems in California. The goal was to elicit perspectives on experiences with end-of-life care and the long-term impact of these experiences. Clinicians were asked to reflect on the different stages of the pandemic, and interviews were analyzed using a thematic analysis., Results: The interviews highlighted 2 primary themes around provision of end-of-life care during the COVID-19 pandemic. First, clinicians described challenges around their clinical duties of providing care to dying patients, which included decision-making dilemmas and professionalism challenges. Second, clinicians described the emotional aspects around end-of-life care situations they experienced, including communication with family members, "being patients' family members" at the end of life, and various degrees of meaning-making and remembrance of these experiences., Conclusions: The findings highlight the sustained and cumulative emotional challenges and burden clinicians are still shouldering more than 2 years after the start of the pandemic., (©2023 American Association of Critical-Care Nurses.)

The canonical autophagy pathway in mammalian cells sequesters diverse cytoplasmic cargo within the double membrane autophagosomes that eventually convert into degradative compartments via fusion with endolysosomal intermediates. Here, we report that autophagosomal membranes show permeability in cells lacking principal ATG8 proteins (mATG8s) and are unable to mature into autolysosomes. Using a combination of methods including a novel in vitro assay to measure membrane sealing, we uncovered a previously unappreciated function of mATG8s to maintain autophagosomal membranes in a sealed state. The mATG8 proteins GABARAP and LC3A bind to key ESCRT-I components contributing, along with other ESCRTs, to the integrity and imperviousness of autophagic membranes. Autophagic organelles in cells lacking mATG8s are permeant, are arrested as amphisomes, and do not progress to functional autolysosomes. Thus, autophagosomal organelles need to be maintained in a sealed state in order to become lytic autolysosomes., (© 2023 The Authors.)

The one-year U.S. Equity-First Vaccination Initiative (EVI), launched in April 2021, aimed to reduce racial inequities in coronavirus disease 2019 (COVID-19) vaccination across five demonstration cities (Baltimore, Chicago, Houston, Newark, and Oakland) and over the longer term strengthen the United States' public health system to achieve more-equitable outcomes. This initiative comprised nearly 100 community-based organizations (CBOs), who led hyper-local work to increase vaccination access and confidence in communities of individuals who identify as Black, Indigenous, and People of Color. In this study, the second of two on the initiative, the authors examine the results of the EVI. They look at the initiative's activities, effects, and challenges, and provide recommendations for how to support and sustain this hyper-local community-led approach and strengthen the public health system in the United States., (Copyright © 2023 RAND Corporation.)

The COVID-19 pandemic in New York City led to the forced rapid transformation of the medical school curriculum as well as increased critical needs to the health system. In response, a group of faculty and student leaders at CUIMC developed the COVID-19 Student Service Corps (Columbia CSSC). The CSSC is an interprofessional service-learning organization that galvanizes the skills and expertise of faculty and students from over 12 schools and programs in the response to the COVID-19 pandemic, and is agile enough to shift and respond to future public health and medical emergencies. Since March 2020, over 30 projects have been developed and implemented supporting needs identified by the health system, providers, faculty, staff, and students as well as the larger community. The development of the CSSC also provided critical virtual educational opportunities in the form of service learning for students who were unable to have any in-person instruction. The CSSC model has been shared nationally and nine additional chapters have started at academic institutions across the country., Competing Interests: The authors have no conflicts of interest to report., (© 2020 The Authors. FASEB BioAdvances published by the Federation of American Societies for Experimental Biology.)

Lysosomal damage activates AMPK, a regulator of macroautophagy/autophagy and metabolism, and elicits a strong ubiquitination response. Here we show that the cytosolic lectin LGALS9 detects lysosomal membrane breach by binding to lumenal glycoepitopes, and directs both the ubiquitination response and AMPK activation. Proteomic analyses have revealed increased LGALS9 association with lysosomes, and concomitant changes in LGALS9 interactions with its newly identified partners that control ubiquitination-deubiquitination processes. An LGALS9-inetractor, deubiquitinase USP9X, dissociates from damaged lysosomes upon recognition of lumenal glycans by LGALS9. USP9X's departure from lysosomes promotes K63 ubiquitination and stimulation of MAP3K7/TAK1, an upstream kinase and activator of AMPK hitherto orphaned for a precise physiological function. Ubiquitin-activated MAP3K7/TAK1 controls AMPK specifically during lysosomal injury, caused by a spectrum of membrane-damaging or -permeabilizing agents, including silica crystals, the intracellular pathogen Mycobacterium tuberculosis , TNFSF10/TRAIL signaling, and the anti-diabetes drugs metformin. The LGALS9-ubiquitin system activating AMPK represents a novel signal transduction system contributing to various physiological outputs that are under the control of AMPK, including autophagy, MTOR, lysosomal maintenance and biogenesis, immunity, defense against microbes, and metabolic reprograming., Abbreviations: AMPK: AMP-activated protein kinase; APEX2: engineered ascorbate peroxidase 2; ATG13: autophagy related 13; ATG16L1: autophagy related 16 like 1; BMMs: bone marrow-derived macrophages; CAMKK2: calcium/calmodulin dependent protein kinase kinase 2; DUB: deubiquitinase; GPN: glycyl-L-phenylalanine 2-naphthylamide; LLOMe: L-leucyl-L-leucine methyl ester; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MERIT: membrane repair, removal and replacement; MTOR: mechanistic target of rapamycin kinase; STK11/LKB1: serine/threonine kinase 11; TNFSF10/TRAIL: TNF superfamily member 10; USP9X: ubiquitin specific peptidase 9 X-linked.