关键词： COVID-19   Innate immunity   Inflammation   NF-κB   TOMM34  

摘要： SummaryBackgroundHighly pathogenic respiratory RNA viruses such as SARS-CoV-2 and its associated syndrome COVID-19 pose a tremendous threat to the global public health. Innate immune responses to SARS-CoV-2 depend mainly upon the NF-κB-mediated inflammation. Identifying unknown host factors driving the NF-κB activation and inflammation is crucial for the development of immune intervention strategies. MethodsPublished single-cell RNA sequencing (scRNA-seq) data was used to analyze the differential transcriptome profiles of bronchoalveolar lavage (BAL) cells between healthy individuals ( n = 27) and patients with severe COVID-19 ( n = 21), as well as the differential transcriptome profiles of peripheral blood mononuclear cells (PBMCs) between healthy individuals ( n = 22) and severely ill patients with COVID-19 ( n = 45) or influenza ( n = 16). Loss-of-function and gain-of-function assays were performed in diverse viruses-infected cells and male mice models to identify the role of TOMM34 in antiviral innate immunity. FindingsTOMM34, together with a list of genes encoding pro-inflammatory cytokines and antiviral immune proteins, was transcriptionally upregulated in circulating monocytes, lung epithelium and innate immune cells from individuals with severe COVID-19 or influenza. Deficiency of TOMM34/Tomm34 significantly impaired the type I interferon responses and NF-κB-mediated inflammation in various human/murine cell lines, murine bone marrow-derived macrophages (BMDMs) and in vivo. Mechanistically, TOMM34 recruits TRAF6 to facilitate the K63-linked polyubiquitination of NEMO upon viral infection, thus promoting the downstream NF-κB activation. InterpretationIn this study, viral induction of TOMM34 is positively correlated with the hyperinflammation in severely ill patients with COVID-19 and influenza. Our findings also highlight the physiological role of TOMM34 in the innate antiviral signallings. FundingA full list of funding sources can be found in the acknowledge

关键词： Individual differences   Loneliness   Mentalization   Reflective functioning   Protective factor   LONELINESS   MENTALIZATION   METAANALYSIS  

摘要： Introduction: Loneliness is a pressing public mental health issue. So far, there has been a paucity of investigations focused on the individual differences modulating this subjective feeling in the face of difficult circumstances, e.g., the COVID-19 pandemic. As such, the present study aimed to investigate the role of mentalization; given that the construct comprises reflection abilities that might be particularly relevant to the pandemic's interpersonal challenges. Methods: A survey representative of the German population was conducted from May to June 2020 (N = 2503). We examined mentalization, operationalized as reflective functioning (RF) and measured using the Mentalization Questionnaire (MZQ), both as a protective factor against loneliness on its own and as a moderator of the association of social isolation with loneliness. Results: Of the overall sample, 822 (32.8 %) individuals reported social isolation. Worse RF was moderately associated with higher levels of loneliness (r = 0.433, p < .001). A linear regression model (controlling for sociodemographic characteristics and general personality pathology) confirmed this positive association, but also indicated an interaction effect of RF and social isolation in the statistical prediction of loneliness. Stratified models showed that RF was a comparatively weaker statistical predictor of loneliness among the socially isolated. Discussion: This representative population study expanded our knowledge about the factors shaping loneliness in the population. RF emerged as a potentially modifiable protective influence. Further research needs to clarify the mechanisms through which it mitigates loneliness.

关键词： Hurricane Laura   COVID-19   Noncongregate sheltering   Improvisation   DISASTER MITIGATION   DECISION-MAKING   EARTHQUAKE RISK   PREPAREDNESS   PLANS  

摘要： Hurricane Laura made landfall in August of 2020 as a Category 4 storm, heavily affecting the coastlines of Texas and Louisiana. At the same time, both areas were coping with a surge in COVID-19 cases absent a vaccine. For this study, we explored how emergency management stakeholders navigated evacuation, sheltering, and re-entry planning and operations during a dual hazard threat where hurricane risk reduction measures contradicted COVID-19 risk reduction measures. We conducted 35 semi-structured interviews with emergency management stakeholders in Texas and Louisiana in the spring of 2021. Participants were recruited using a purposive sampling strategy designed to identify agency representatives and other officials involved with planning for hurricane season and with the Hurricane Laura response effort. We used thematic analysis to code and analyze the data. Findings suggest that while the process for planning for hurricanes had to shift to an online approach, the plan for addressing hurricane season was largely unchanged from the perspective of most participants until days before impact, when the decision was made to move to noncongregate sheltering. This led to adaptive and creative improvisation on the part of participants managing the evacuation and sheltering operations. Likewise, we found that caring for and communicating with evacuees in a noncongregate setting presented unanticipated challenges that required improvisation to address. Given the continued threat posed by COVID-19 and other respiratory illnesses, this study provides insights that emergency management stakeholders could apply to current and future planning and response efforts for hazards that require evacuation and sheltering.