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Abstract Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration

Abstract Improving sleep quality in patients with obstructive sleep apnea (OSA) by positive airway pressure therapy is associated with a decrease of blood pressure (BP). It remains elusive, whether treatment of sleep disturbances due to restless legs syndrome with symptomatic periodic limb movements in sleep (PLMS) affects BP as well. The present study provides first data on this issue. Retrospective study on patients undergoing polysomnography in a German University Hospital. Inclusion criteria were first diagnosis of restless legs syndrome with PLMS (PLM index ≥ 15/h and PLM arousal index ≥ 5/h) with subsequent initiation of levodopa/benserazide or dopamine agonists. Exclusion criterion was an initiation or change of preexisting positive airway pressure therapy between baseline and follow-up. BP and Epworth sleepiness scale were assessed at two consecutive polysomnographies. After screening of 953 PLMS data sets, 114 patients (mean age 62.1 ± 12.1 years) were included. 100 patients (87.7%) were started on levodopa/benserazide, 14 patients (12.2%) on dopamine agonists. Treatment was associated with significant reductions of PLM index (81.2 ± 65.0 vs. 39.8 ± 51.2, p

Abstract Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.

The intersection of the Foundation Plume with the Pacific-Antarctic Ridge is a key location in global geodynamics where a mantle plume is approached by and interacting with a fast-spreading mid-ocean ridge. Here, we discuss a comprehensive major and trace element and Sr-Nd-Pb isotope dataset of new and existing samples from the young Foundation Seamount Chain (<5 Ma) and adjacent section of the Pacific-Antarctic Ridge. We use the geochemistry of axial, off-axis and intraplate lavas to map the spatial extent of plume dispersal underneath the ridge as well as the internal zonation of the upwelling plume. We show that the unusual length, increased crustal thickness and occurrence of silicic rocks on the axis of the Foundation Segment are the direct result of plume being tapped by the axial melting zone. We demonstrate that the plume is not homogeneous but shows a HIMU-like (high time-integrated [sup 238]U/[sup 204]Pb) OIB (Ocean Island Basalt) component characterized by [sup 206]Pb/[sup 204]Pb of up to 20.5 in its center and a more EM1-like (Enriched Mantle one) OIB component characterized by low U/Pb and [sup 206]Pb/[sup 204]Pb but high Rb/Nb and [sup 87]Sr/[sup 86]Sr towards its edges. Plume entrainment leads to a high magma supply rate that fosters the formation of silicic rocks and triggers the lengthening of the segment over time. However, plume dispersal is not symmetric as the geochemical tracers for the OIB component are extending <100 km northwards but >300 km southwards. We relate this to the current plate tectonic framework in which the obliquity between the migrating ridge and the absolute plate motions induces a sub-axial asthenospheric flow that preferentially channels plume material southwards. [ABSTRACT FROM AUTHOR]

At the quadrangular joint (QAJ) of the carpus, a rare bony protuberance called carpal boss (CB) may occur. This bone abnormality may be due to osteophytes development or os styloideum. Symptomatic patients may complain pain, swelling, and restrictions in hand motion. These symptoms result from joint degenerative‐inflammatory changes, development of ganglion cyst/bursitis, or tendons pathology. Correct diagnosis and appropriate management can be achieved through high‐resolution ultrasonography (HR‐US). The purpose of this review is to define the pathology spectrum around and within the QAJ in CB. The role of HR‐US is highlighted and the standard technique for the QAJ assessment is described. [ABSTRACT FROM AUTHOR]

Importance: Staphylococcus aureus frequently colonizes the skin and nose of patients with atopic dermatitis (AD), a disease associated with skin barrier dysfunction and chronic cutaneous inflammation. Published genomic studies on AD-associated S. aureus in pediatric populations in sub-Saharan Africa are limited. Objectives: To investigate the phenotypic and genomic diversity of S. aureus in children with and without AD during early childhood. Data, setting and participants: A cross-sectional study of 220 children (aged 9-38 months) with AD (cases) and without AD (controls) from Cape Town and Umtata, South Africa. Main outcomes and measures: S. aureus phenotypic and genomic diversity were investigated using whole-genome sequencing, antibiotic susceptibility testing and biofilm microtiter assay. Results: Of the 124 S. aureus isolates recovered from 220 children, 96 isolates (79 cases and 17 controls) with high-quality sequences were analyzed. Isolates from cases showed greater phenotypic resistance to gentamicin (10%), rifampicin (4%), chloramphenicol (4%), and exhibited multidrug resistance (9%) than in controls. Furthermore, the isolates from cases formed stronger biofilms than those from controls (76% vs. 35%, p = 0.001), but showed no dominance of any virulence factor gene or mobile genetic elements. There was no significant difference in the distribution of immune evasion cluster types between cases and controls. However, IEC type G was identified only among cases. Conclusion and relevance: AD-associated S. aureus has phenotypic and genetic features that are important for successful pathogenic colonization and survival. Further studies are needed to assess the pathological implications of colonization of various S. aureus lineages in vivo to elucidate their pathological contribution to AD pathogenesis and pathophysiology. [ABSTRACT FROM AUTHOR]

BackgroundMicrobiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD.MethodsWe performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography.ResultsThe study included 1,253 patients (median [IQR], 67 [58–76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 μM, IQR, 4.1–7.6) compared to the non-CAD groups 6.53 μM (4.6–8.6, p

Urban data deficits in developing countries impede evidence-based planning and policy. Could energy data be used to overcome this challenge by serving as a local proxy for living standards or economic activity in large urban areas? To answer this question, we examine the potential of georeferenced residential electricity meter data and night-time lights (NTL) data in the megacity of Karachi, Pakistan. First, we use nationally representative survey data to establish a strong association between electricity consumption and household living standards. Second, we compare gridded radiance values from NTL data with a unique dataset containing georeferenced median monthly electricity consumption values for over 2 million individual households in the city. Finally, we develop a model to explain intra-urban variation in radiance values using proxy measures of economic activity from Open Street Map. Overall, we find that NTL data are a poor proxy for living standards but do capture spatial variation in population density and economic activity. By contrast, electricity data are an excellent proxy for living standards and could be used more widely to inform policy and support poverty research in cities in low- and middle-income countries.

High resolution poverty mapping supports evidence-based policy and research, yet about half of all countries lack the survey data needed to generate useful poverty maps. To overcome this challenge, new non-traditional data sources and deep learning techniques are increasingly used to create small-area estimates of poverty in low- and middle-income countries (LMICs). Convolutional Neural Networks (CNN) trained on satellite imagery are emerging as one of the most popular and effective approaches. However, the spatial resolution of poverty estimates has remained relatively coarse, particularly in rural areas. To address this problem, we use a transfer learning approach to train three CNN models and use them in an ensemble to predict chronic poverty at 1 km2 scale in rural Sindh, Pakistan. The models are trained with spatially noisy georeferenced household survey containing poverty scores for 1.67 million anonymized households in Sindh Province and publicly available inputs, including daytime and nighttime satellite imagery and accessibility data. Results from both hold-out and k-fold validation exercises show that the ensemble provides the most reliable spatial predictions in both arid and non-arid regions, outperforming previous studies in key accuracy metrics. A third validation exercise, which involved ground-truthing of predictions from the ensemble model with original survey data of 7000 households further confirms the relative accuracy of the ensemble model predictions. This inexpensive and scalable approach could be used to improve poverty targeting in Pakistan and other low- and middle-income countries.

Social network sites (SNSs) have become ubiquitous around the globe and interwoven with all aspects of life. In this article, I will argue that the communicative infrastructure of SNSs, i.e., all SNS-elements that allow users to communicate, is a key element for understanding their impact as it creates environments in which users, their behaviors, and social interactions are embedded. These digital environments facilitate and encourage fundamental mechanisms of implicit learning from feedback as well as observation in an unprecedented way. I will discuss how these technology-based learning environments impact the mental health of their users, e.g., by linking negative online feedback to depression and following influencers to disturbed eating. The article ends with a conclusion that emphasizes the advantages of understanding SNSs as environments in order to reflect the complexity, relevance, and ubiquitousness of the phenomenon.

Abstract Background Individuals receiving means-tested benefits are at a higher risk of being diagnosed with a psychiatric illness compared to those who are employed, and the rate of those working in the first labor market is low. The intervention (Individual Placement and Support, IPS) aims at maintaining or regaining working ability and at facilitating reintegration into the (first) labor market following a “first place, then train”-approach. The objective of the study is to conduct the first RCT in Germany that addresses a broad group of long-term unemployed individuals with severe mental illnesses that receive means-tested benefits, and to test the effectiveness of the IPS intervention. Methods In this randomized controlled trial, about 120 eligible participants aged between 18 years and local retirement age will be randomly allocated to an intervention group (IG) or to an active control group (CG) using a parallel arm design. The IG will receive IPS + high quality treatment as usual (TAU), the active CG will receive TAU + a booklet on integration measures. A block-randomization algorithm with a targeted assignment ratio of 1:1 for participants in IG and active CG will be used, stratified by sex and three age groups. Assessments will take place before the intervention at baseline (t0), and 6 (t1), 12 (t2), and 18 (t3) months later. Primary outcome will be the proportion of participants having worked at least 1 day in competitive employment since baseline, as assessed at t3. Secondary outcomes will be related to employment/ vocation and mental health. In addition, there will be a process evaluation. Treatment effects on outcomes will be tested using appropriate panel-data regression models, and acceptability, uptake and adherence will be evaluated using descriptive statistics and appropriate inference testing. Discussion The results of this trial are expected to generate a better understanding of the efficiency, feasibility, acceptance, and relevance of the IPS intervention in a German setting. They could be a first step towards the implementation of the method and towards improving the situation of long-term unemployed individuals with severe mental health problems. Trial registration German Clinical Trials Register ( DRKS00023245 ), registered on 22.02.2021.

Abstract Anxiety is a widespread phenomenon that affects various behaviors. We want to analyze in how far anxiety is connected to eating behaviors since this is one potential pathway to understanding eating-related health outcomes like obesity or eating disorders. We used data from the population-based LIFE-Adult-Study (n = 5019) to analyze the connection between anxiety (GAD-7) and the three dimensions of eating behaviors (FEV)—Cognitive Restraint, Disinhibition, and Hunger—while controlling for sociodemographic variables, smoking, physical activity, personality, and social support. Multivariate regression analyses showed significant positive associations between anxiety and Disinhibition as well as Hunger, but not between anxiety and Cognitive Restraint. Interventions that help individuals to better regulate and cope with anxiety, could be one potential pathway to reducing eating disorders and obesity in the population.

Abstract Background We want to analyze the effect of migration background (MB) on physician burnout and work-life balance. Methods In September 2019, physicians from various specialties answered a questionnaire on work and health. We analyzed a subsample of 526 physicians that were working full time in a hospital, 14% with an MB and 47.9% were female. Results Multivariate analysis showed that physicians with an MB exhibit significantly less favorable scores on all three burnout dimensions, and this effect persisted in the regression analysis after adding age, gender, and marital status as control variables. There were no differences with regard to work-life balance. Conclusions To our knowledge, our study is the first one to suggest that MB plays a significant role in physician mental health. Future research will benefit from identifying the factors behind that connection, e.g., problems related to acculturation, communication and social integration, which can then be addressed by policymakers in order to maintain and improve the medical infrastructure.

BackgroundAnxiety is a widespread phenomenon, and it is connected to disordered eating and obesity. We want to analyze the connection between anxiety and food addiction (FA) over two points in time to better understand the directionality of the association. Since there are gender differences with regard to anxiety and eating, we are also interested in differences between men and women.MethodsWe used data from the population-based LIFE-Adult-Study (N = 1,474) at time 1 (baseline) and time 2 (first follow-up) to analyze the connections between anxiety (GAD-7) and FA (YFAS) using a multiple group latent cross-lagged panel model with female and male participants as groups. We controlled for age, marital status, socioeconomic status and social support.ResultsAnxiety (women: β = 0.50, p ≤ 0.001; men: β = 0.59, p ≤ 0.001) as well as FA (women: β = 0.37, p ≤ 0.001; men: β = 0.58, p ≤ 0.001) exhibited stability over time for both genders. We found a significant association between anxiety at time 1 and FA at time 2 for women (β = 0.25, p ≤ 0.001) but not for men (β = 0.04, p = 0.10), and significant associations between FA at time 1 and anxiety at time 2 for women (β = 0.23, p ≤ 0.001) as well as men (β = 0.21, p ≤ 0.001).ConclusionFood addiction longitudinally affects anxiety, independent of gender and other sociodemographic variables. In addition, anxiety affects subsequent FA as well, but only in women. Interventions that address FA could reduce anxiety in men and women, while interventions that mitigate anxiety could help prevent FA in women.

Abstract Background Staphylococcus aureus has been associated with the exacerbation and severity of atopic dermatitis (AD). Studies have not investigated the colonisation dynamics of S. aureus lineages in African toddlers with AD. We determined the prevalence and population structure of S. aureus in toddlers with and without AD from rural and urban South African settings. Methods We conducted a study of AD-affected and non-atopic AmaXhosa toddlers from rural Umtata and urban Cape Town, South Africa. S. aureus was screened from skin and nasal specimens using established microbiological methods and clonal lineages were determined by spa typing. Logistic regression analyses were employed to assess risk factors associated with S. aureus colonisation. Results S. aureus colonisation was higher in cases compared to controls independent of geographic location (54% vs. 13%, p

Abstract The production of peptides as active pharmaceutical ingredients (APIs) by recombinant technologies is of emerging interest. A reliable production platform, however, is still missing due the inherent characteristics of peptides such as proteolytic sensitivity, aggregation and cytotoxicity. We have developed a new technology named Numaswitch solving present limitations. Numaswitch was successfully employed for the production of diverse peptides and small proteins varying in length, physicochemical and functional characteristics, including Teriparatide, Linaclotide, human β-amyloid and Serum amyloid A3. Additionally, the potential of Numaswitch for a cost-efficient commercial production is demonstrated yielding > 2 g Teriparatide per liter fermentation broth in a quality meeting API standard.