Migrant healthcare workers during COVID-19: bringing an intersectional health system-related approach into pandemic protection. A German case study

IntroductionMigrant healthcare workers played an important role during the COVID-19 pandemic, but data are lacking especially for high-resourced European healthcare systems. This study aims to research migrant healthcare workers through an intersectional health system-related approach, using Germany as a case study.MethodsAn intersectional research framework was created and a rapid scoping study performed. Secondary analysis of selected items taken from two COVID-19 surveys was undertaken to compare perceptions of national and foreign-born healthcare workers, using descriptive statistics.ResultsAvailable research is focused on worst-case pandemic scenarios of Brazil and the United Kingdom, highlighting racialised discrimination and higher risks of migrant healthcare workers. The German data did not reveal significant differences between national-born and foreign-born healthcare workers for items related to health status including SARS-CoV-2 infection and vaccination, and perception of infection risk, protective workplace measures, and government measures, but items related to social participation and work conditions with higher infection risk indicate a higher burden of migrant healthcare workers.ConclusionsCOVID-19 pandemic policy must include migrant healthcare workers, but simply adding the migration status is not enough. We introduce an intersectional health systems-related approach to understand how pandemic policies create social inequalities and how the protection of migrant healthcare workers may be improved

The CD8α+ Dendritic Cell Is Responsible for Inducing Peripheral Self-Tolerance to Tissue-associated Antigens

We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow–derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8α+ dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced β-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c+CD8α+ cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8α+ DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self

Molecular Epidemiology of the HIV Epidemic in Three German Metropolitan Regions - Cologne/Bonn, Munich and Hannover, 1999-2016

Using HIV sequence data to characterize clusters of HIV transmission may provide insight into the epidemic. Phylogenetic and network analyses were performed to infer putative relationships between HIV-1 partial pol sequences from 2,774 individuals receiving care in three German regions between 1999-2016. The regions have in common that they host some of the largest annual festivals in Europe (Carnival and Oktoberfest). Putative links with sequences (n = 150,396) from the Los Alamos HIV Sequence database were evaluated. A total of 595/2,774 (21.4%) sequences linked with at least one other sequence, forming 184 transmission clusters. Clustering individuals were significantly more likely to be younger, male, and report sex with men as their main risk factor (p < 0.001 each). Most clusters (77.2%) consisted exclusively of men;41 (28.9%) of these included men reporting sex with women. Thirty-two clusters (17.4%) contained sequences from more than one region;clustering men were significantly more likely to be in a position bridging regional HIV epidemics than clustering women (p = 0.027). We found 236 clusters linking 547 sequences from our sample with sequences from the Los Alamos database (n = 1407;31% from other German centres). These results highlight the pitfalls of focusing HIV prevention efforts on specific risk groups or specific locales

Direction and magnitude of nicotine effects on the fMRI BOLD response are related to nicotine effects on behavioral performance

Considerable variability across individuals has been reported in both the behavioral and fMRI blood oxygen level-dependent (BOLD) response to nicotine. We aimed to investigate (1) whether there is a heterogeneous effect of nicotine on behavioral and BOLD responses across participants and (2) if heterogeneous BOLD responses are associated with behavioral performance measures. In this double-blind, placebo-controlled, cross-over study, 41 healthy participants (19 smokers)—drawn from a larger population-based sample—performed a visual oddball task after acute challenge with 1 mg nasal nicotine. fMRI data and reaction time were recorded during performance of the task. Across the entire group of subjects, we found increased activation in the anterior cingulate cortex, middle frontal gyrus, superior temporal gyrus, post-central gyrus, planum temporal and frontal pole in the nicotine condition compared with the placebo condition. However, follow-up analyses of this difference in activation between the placebo and nicotine conditions revealed that some participants showed an increase in activation while others showed a decrease in BOLD activation from the placebo to the nicotine condition. A reduction of BOLD activation from placebo to nicotine was associated with a decrease in reaction time and reaction time variability and vice versa, suggesting that it is the direction of BOLD response to nicotine which is related to task performance. We conclude that the BOLD response to nicotine is heterogeneous and that the direction of response to nicotine should be taken into account in future pharmaco-fMRI research on the central action of nicotine

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

International AIDS Society global scientific strategy: towards an HIV cure 2016

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

Mitochondrial DNA Depletion and Respiratory Chain Activity in Primary Human Subcutaneous Adipocytes Treated with Nucleoside Analogue Reverse Transcriptase Inhibitors▿

Mitochondrial dysfunction as a consequence of mitochondrial DNA (mtDNA) depletion due to therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) has been proposed as a pathogenic mechanism leading to lipoatrophy in HIV-infected patients. The aim of our study was to investigate the impact of NRTI treatment on mtDNA abundance and the activities of respiratory chain complexes in primary human subcutaneous preadipocytes (phsPA). We studied adipocyte phenotypes, viability, and differentiation (CCAAT/enhancer-binding protein α [C/EBPα] and peroxisome proliferator-activated receptor γ [PPARγ] expression) and adiponectin production, mtDNA content, mitochondrial membrane potential, mitochondrial mass, and respiratory chain enzyme and citrate synthase activities in both proliferating and differentiating phsPA. Cells were exposed to zidovudine (6 μM), stavudine (d4T; 3 μM), and zalcitabine (ddC; 0.1 μM) for 8 weeks. NRTI-induced mtDNA depletion occurred in proliferating and differentiating phsPA after exposure to therapeutic drug concentrations of d4T and ddC. At these concentrations, ddC and d4T led to an almost 50% decrease in the number of mtDNA copies per cell without major impact on adipocyte differentiation. Despite mtDNA depletion by NRTI, the activities of the respiratory chain complexes, the mitochondrial membrane potential, and the mitochondrial mass were found to be unaffected. Severe NRTI-mediated mtDNA depletion in phsPA is not inevitably associated with impaired respiratory chain activity or altered mitochondrial membrane potential