Mental health of individuals with pre-existing mental illnesses at the beginning of the COVID-19 pandemic: results of the German National Cohort (NAKO).

Background: The COVID-19 pandemic prompted a range of studies on mental health, with mixed results. While numerous studies reported worsened conditions in individuals with pre-existing mental disorders, others showed resilience and stability in mental health. However, longitudinal data focusing on the German population are sparse, especially regarding effects of age and pre-existing mental disorders during the early stages of the pandemic. Objectives: To assess the interplay between psychiatric history, age, and the timing of the pandemic, with a focus on understanding how these factors relate to the severity of depression and anxiety symptoms. Methods: Exploratory analyses were based on 135,445 individuals aged 20-72 years from the German National Cohort (NAKO). Depressive and anxiety symptoms were assessed before and after the first wave of the pandemic. Inferential statistical analyses and negative binomial regression models were calculated. Results: Persons with a self-reported psychiatric history exhibited comparable levels of depression and anxiety symptom severity after the first wave of the pandemic compared to the time before. In contrast, individuals without a psychiatric history, particularly those in their 20s to 40s, experienced an increase in mental health symptom severity during the first wave of the pandemic. Limitations: Analyses focuses on the first wave of the pandemic, leaving the long-term mental health effects unexplored. Conclusion: Future research should consider age-specific and mental-health-related factors when addressing global health crises. Additionally, it is important to explore factors influencing resilience and adaptation, aiming to develop targeted interventions and informed policies for effective mental health management during pandemics.

CODI: Enhancing machine learning-based molecular profiling through contextual out-of-distribution integration.

Molecular analytics increasingly utilize machine learning (ML) for predictive modeling based on data acquired through molecular profiling technologies. However, developing robust models that accurately capture physiological phenotypes is challenged by the dynamics inherent to biological systems, variability stemming from analytical procedures, and the resource-intensive nature of obtaining sufficiently representative datasets. Here, we propose and evaluate a new method: Contextual Out-of-Distribution Integration (CODI). Based on experimental observations, CODI generates synthetic data that integrate unrepresented sources of variation encountered in real-world applications into a given molecular fingerprint dataset. By augmenting a dataset with out-of-distribution variance, CODI enables an ML model to better generalize to samples beyond the seed training data, reducing the need for extensive experimental data collection. Using three independent longitudinal clinical studies and a case-control study, we demonstrate CODI's application to several classification tasks involving vibrational spectroscopy of human blood. We showcase our approach's ability to enable personalized fingerprinting for multiyear longitudinal molecular monitoring and enhance the robustness of trained ML models for improved disease detection. Our comparative analyses reveal that incorporating CODI into the classification workflow consistently leads to increased robustness against data variability and improved predictive accuracy.

The spine-brain axis: is spinal anatomy associated with brain volume?

First small sample studies indicate that disturbances of spinal morphology may impair craniospinal flow of cerebrospinal fluid and result in neurodegeneration. The aim of this study was to evaluate the association of cervical spinal canal width and scoliosis with grey matter, white matter, ventricular and white matter hyperintensity volumes of the brain in a large study sample. Four hundred participants underwent whole-body 3 T magnetic resonance imaging. Grey matter, white matter and ventricular volumes were quantified using a warp-based automated brain volumetric approach. Spinal canal diameters were measured manually at the cervical vertebrae 2/3 level. Scoliosis was evaluated using manual measurements of the Cobb angle. Linear binomial regression analyses of measures of brain volumes and spine anatomy were performed while adjusting for age, sex, hypertension, cholesterol levels, body mass index, smoking and alcohol consumption. Three hundred eighty-three participants were included [57% male; age: 56.3 (±9.2) years]. After adjustment, smaller spinal canal width at the cervical vertebrae 2/3 level was associated with lower grey matter (P = 0.034), lower white matter (P = 0.012) and higher ventricular (P = 0.006, inverse association) volume. Participants with scoliosis had lower grey matter (P = 0.005), lower white matter (P = 0.011) and larger brain ventricular (P = 0.003) volumes than participants without scoliosis. However, these associations were attenuated after adjustment. Spinal canal width at the cervical vertebrae 2/3 level and scoliosis were not associated with white matter hyperintensity volume before and after adjustment (P > 0.864). In our study, cohort smaller spinal canal width at the cervical vertebrae 2/3 level and scoliosis were associated with lower grey and white matter volumes and larger ventricle size. These characteristics of the spine might constitute independent risk factors for neurodegeneration.

What is the relationship between risk attitudes and ambient temperature? Evidence from a large population-based cohort study.

Rising temperatures affect human behavior and risk-taking in several domains. However, it is not yet well understood just how ambient temperature shapes risk attitudes. Using data from the large population-based KORA-Fit study (Cooperative Health Research in the Region of Augsburg) of older people (N=2454), we identify a statistically significant, but very small, positive association between short-term ambient temperature changes and individuals' general willingness to take risks. Health-related risk attitudes, however, show no significant relationship with temperature. These findings support a domain-specific view of risk attitudes, with results remaining consistent for vulnerable individuals with the chronic conditions diabetes, hypertension, and asthma. Overall, our findings suggest that risk attitudes are somewhat stable towards changes in ambient temperature.

SoccHealth: a health status examination of former professional football (soccer) players within the German National Cohort.

The long-term health effects of football (soccer) have received significant attention in recent years. While brain health is currently the focus of this interest, potential long-term risks or benefits related to cardiovascular and metabolic diseases and cancer are also of interest to sports medicine professionals. However, studies assessing the overall health risks for professional football players remain scarce. We introduce 'SoccHealth', a satellite project to the German National Cohort (NAKO), Germany's largest population-based cohort study. SoccHealth examined 348 former professional football players aged 40-69 using the infrastructure and comprehensive examination programme of NAKO. The German Statutory Accidental Insurance for Professional Athletes identified and invited male players, while female players were recruited among former national team members. Details of the examination programme and the sociodemographic and career-related characteristics of the participants are described. The identical examination programme for the NAKO participants provides the opportunity to draw general population controls according to various definitions and focus on the respective research question to be analysed. This report delineates one approach to evaluate the long-term health effects of football across a broad range of diseases.

Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity.

Type 2 diabetes (T2D) and obesity are strongly associated with low natriuretic peptide (NP) plasma levels and a down-regulation of NP guanylyl cyclase receptor-A (GCA) in skeletal muscle and adipose tissue. However, no study has so far provided evidence for a causal link between atrial NP (ANP)/GCA deficiency and T2D pathogenesis. Here, we show that both systemic and skeletal muscle ANP/GCA deficiencies in mice promote metabolic disturbances and prediabetes. Skeletal muscle insulin resistance is further associated with altered mitochondrial function and impaired endurance running capacity. ANP/GCA-deficient mice exhibit increased proton leak and reduced content of mitochondrial oxidative phosphorylation proteins. We further show that GCA is related to several metabolic traits in T2D and positively correlates with markers of oxidative capacity in human skeletal muscle. Together, these results indicate that ANP/GCA signaling controls muscle mitochondrial integrity and oxidative capacity in vivo and plays a causal role in the development of prediabetes.

Association between Long-Term Exposure to Traffic-Related Air Pollution and Cardio-Metabolic Phenotypes: An MRI Data-Based Analysis.

Long-term exposure to traffic-related air pollution (TRAP) is associated with cardiometabolic disease; however, its role in subclinical stages of disease development is unclear. Thus, we aimed to explore this association in a cross-sectional analysis, with cardiometabolic phenotypes derived from magnetic resonance imaging (MRI). Phenotypes of the left (LV) and right cardiac ventricle, whole-body adipose tissue (AT), and organ-specific AT were obtained by MRI in 400 participants of the KORA cohort. Land-use regression models were used to estimate residential long-term exposures to TRAP, e.g., nitrogen dioxides (NO2) or particle number concentration (PNC). Associations between TRAP and MRI phenotypes were modeled using linear regression. Participants' mean age was 56 ± 9 years, and 42% were female. Long-term exposure to TRAP was associated with decreased LV wall thickness; a 6.0 µg/m3 increase in NO2 was associated with a -1.9% [95% confidence interval: -3.7%; -0.1%] decrease in mean global LV wall thickness. Furthermore, we found associations between TRAP and increased cardiac AT. A 2,242 n/cm3 increase in PNC was associated with a 4.3% [-1.7%; 10.4%] increase in mean total cardiac AT. Associations were more pronounced in women and in participants with diabetes. Our exploratory study indicates that long-term exposure to TRAP is associated with subclinical cardiometabolic disease states, particularly in metabolically vulnerable subgroups.

Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study.

BACKGROUND AND AIMS: Understanding molecular processes of the early phase of atherosclerotic cardiovascular disease conditions is of utmost importance for early prediction and intervention measures. METHODS: We measured 92 cardiovascular-disease-related proteins (Olink, Cardiovascular III) in 2024 elderly participants of the population-based LIFE-Adult study. We analysed the impact of 27 covariables on these proteins including blood counts, cardiovascular risk factors and life-style-related parameters. We also analysed protein associations with 13 subclinical cardiovascular traits comprising carotid intima media thickness, plaque burden, three modes of Vicorder-based pulse-wave velocities, ankle-brachial index and ECLIA-based N-terminal prohormone of brain natriuretic peptide (NT-proBNP). RESULTS: Estimated glomerular filtration rate, triglycerides and sex where the most relevant covariables explaining more than 1 % variance of 49, 22 and 20 proteins, respectively. A total of 43 proteins were significantly associated with at least one of the analysed subclinical cardiovascular traits. NT-pro-BNP, brachial-ankle pulse-wave velocity (baPWV) and parameters of carotid plaque burden accounted for the largest number of associations. Association overlaps were relatively sparse. Only growth/differentiation factor 15, low density lipoprotein receptor and interleukin-1 receptor type 2 are associated with these three different cardiovascular traits. We confirmed several literature findings and found yet unreported associations for carotid plaque presence (von-Willebrand factor, galectin 4), carotid intima-media thickness (carboxypeptidase A1 andB1), baPWV (cathepsin D) and NT-proBNP (cathepsin Z, low density lipoprotein receptor, neurogenic locus homolog protein 3, trem-like transcript 2). Sex-interaction effects were observed, e.g. for spondin-1 and growth/differentiation factor 15 likely regulated by androgen response elements. CONCLUSIONS: We extend the catalogue of proteome biomarkers possibly involved in early stages of cardiovascular disease pathologies providing targets for early risk prediction or intervention strategies.

Temporal variations in the short-term effects of ambient air pollution on cardiovascular and respiratory mortality: a pooled analysis of 380 urban areas over a 22-year period.

BACKGROUND: Ambient air pollution, including particulate matter (such as PM10 and PM2·5) and nitrogen dioxide (NO2), has been linked to increases in mortality. Whether populations' vulnerability to these pollutants has changed over time is unclear, and studies on this topic do not include multicountry analysis. We evaluated whether changes in exposure to air pollutants were associated with changes in mortality effect estimates over time. METHODS: We extracted cause-specific mortality and air pollution data collected between 1995 and 2016 from the Multi-Country Multi-City (MCC) Collaborative Research Network database. We applied a two-stage approach to analyse the short-term effects of NO2, PM10, and PM2·5 on cause-specific mortality using city-specific time series regression analyses and multilevel random-effects meta-analysis. We assessed changes over time using a longitudinal meta-regression with time as a linear fixed term and explored potential sources of heterogeneity and two-pollutant models. FINDINGS: Over 21·6 million cardiovascular and 7·7 million respiratory deaths in 380 cities across 24 countries over the study period were included in the analysis. All three air pollutants showed decreasing concentrations over time. The pooled results suggested no significant temporal change in the effect estimates per unit exposure of PM10, PM2·5, or NO2 and mortality. However, the risk of cardiovascular mortality increased from 0·37% (95% CI -0·05 to 0·80) in 1998 to 0·85% (0·55 to 1·16) in 2012 with a 10 µg/m3 increase in PM2·5. Two-pollutant models generally showed similar results to single-pollutant models for PM fractions and indicated temporal differences for NO2. INTERPRETATION: Although air pollution levels decreased during the study period, the effect sizes per unit increase in air pollution concentration have not changed. This observation might be due to the composition, toxicity, and sources of air pollution, as well as other factors, such as socioeconomic determinants or changes in population distribution and susceptibility. FUNDING: None.

Associations of occupational and leisure-time physical activity with all-cause mortality: an individual participant data meta-analysis.

OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

Association of plasma proteomics with mortality in individuals with and without type 2 diabetes: Results from two population-based KORA cohort studies.

BACKGROUND: Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause mortality in two prospective Cooperative Health Research in the Region of Augsburg (KORA) studies. METHODS: The discovery cohort comprised 1545 participants (median follow-up 15.6 years; 244 with T2D: 116 total, 62 cardiovascular, 31 cancer-related and 23 other-cause deaths; 1301 without T2D: 321 total, 114 cardiovascular, 120 cancer-related and 87 other-cause deaths). The validation cohort comprised 1031 participants (median follow-up 6.9 years; 203 with T2D: 76 total, 45 cardiovascular, 19 cancer-related and 12 other-cause deaths; 828 without T2D: 169 total, 74 cardiovascular, 39 cancer-related and 56 other-cause deaths). We used Cox regression to examine associations of 233 plasma proteins with all-cause and cause-specific mortality and Lasso regression to construct prediction models for all-cause mortality stratifying by baseline T2D. C-index, category-free net reclassification index (cfNRI), and integrated discrimination improvement (IDI) were conducted to evaluate the predictive performance of built prediction models. RESULTS: Thirty-five and 62 proteins, with 29 overlapping, were positively associated with all-cause mortality in the group with and without T2D, respectively. Out of these, in the group with T2D, 35, eight, and 26 were positively associated with cardiovascular, cancer-related, and other-cause mortality, while in the group without T2D, 55, 41, and 47 were positively associated with respective cause-specific outcomes in the pooled analysis of both cohorts. Regulation of insulin-like growth factor (IGF) transport and uptake by IGF-binding proteins emerged as a unique pathway enriched for all-cause and cardiovascular mortality in individuals with T2D. The combined model containing the selected proteins (five and 12 proteins, with four overlapping, in the group with and without T2D, respectively) and clinical risk factors improved the prediction of all-cause mortality by C-index, cfNRI, and IDI. CONCLUSIONS: This study uncovered shared and unique mortality-related proteins in persons with and without T2D and emphasized the role of proteins in improving the prediction of mortality in different T2D subgroups.

Should workers be physically active after work? Associations of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels-An individual participant data meta-analysis.

BACKGROUND: There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels. This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels. METHODS: This study utilized individual participant data from 21 cohort studies, comprising both published and unpublished data. Eligibility criteria included individual-level data on leisure-time and occupational physical activity (categorized as sedentary, low, moderate, and high) along with data on all-cause and/or cardiovascular mortality. A 2-stage individual participant data meta-analysis was conducted, with separate analysis of each study using Cox proportional hazards models (Stage 1). These results were combined using random-effects models (Stage 2). RESULTS: Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels, for both males and females. Among males with sedentary work, high compared to sedentary leisure-time physical activity was associated with lower all-cause (hazard ratios (HR) = 0.77, 95% Confidence interval(95%CI): 0.70-0.85) and cardiovascular mortality (HR = 0.76, 95%CI: 0.66-0.87) risk. Among males with high levels of occupational physical activity, high compared to sedentary leisure-time physical activity was associated with lower all-cause (HR = 0.84, 95%CI: 0.74-0.97) and cardiovascular mortality (HR = 0.79, 95%CI: 0.60-1.04) risk, while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant. Among females, most effects were similar but more imprecise, especially in the higher occupational physical activity levels. CONCLUSION: Higher levels of leisure-time physical activity were generally associated with lower mortality risks. However, results for workers with moderate and high occupational physical activity levels, especially women, were more imprecise. Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity, irrespective of their level of occupational physical activity.

Heat and cause-specific cardiopulmonary mortality in Germany: a case-crossover study using small-area assessment.

Background: High temperatures have been associated with increased mortality, with evidence reported predominately in large cities and for total cardiovascular or respiratory deaths. This case-crossover study examined heat-related cause-specific cardiopulmonary mortality and vulnerability factors using small-area data from Germany. Methods: We analyzed daily counts of cause-specific cardiopulmonary deaths from 380 German districts (2000-2016) and daily mean temperatures estimated by spatial-temporal models. We applied conditional quasi-Poisson regression using distributed lag nonlinear models to examine heat effects during May-September in each district and random-effects meta-analysis to pool the district-specific estimates. Potential individual- and district-level vulnerability factors were examined by subgroup analyses and meta-regressions, respectively. Findings: Heat was associated with increased mortality risks for all cardiopulmonary sub-causes. The relative risk (RR) of total cardiovascular and respiratory mortality for a temperature increment from the 75th to the 99th percentile was 1.24 (95% confidence interval: 1.23, 1.26) and 1.34 (1.30, 1.38), respectively. The RRs of cardiovascular sub-causes ranged from 1.16 (1.13, 1.19) for myocardial infarction to 1.32 (1.29, 1.36) for heart failure. For respiratory sub-causes, the RR was 1.27 (1.22, 1.31) for COPD and 1.49 (1.42, 1.57) for pneumonia. We observed greater susceptibility related to several individual- and district-level characteristics, e.g., among females or in highly urbanized districts. Heat vulnerability factors remained consistent between urban and rural areas. Interpretation: Our study highlights heat-related increases in cause-specific cardiopulmonary mortality across Germany and identifies key vulnerability factors, offering insights for improving public health practices to mitigate heat-related health impacts. Funding: European Union's Horizon 2020 research and innovation program; Helmholtz Associations Initiative and Networking Fund.

Subclinical impairment of the left atrium is associated with MRI-based lung volume but not with parameters from pulmonary function testing.

Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = - 0.03, p = 0.006; ß = - 0.03, p = 0.021; ß = - 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.

Socioeconomic Inequalities in the External Exposome in European Cohorts: The EXPANSE Project.

Socioeconomic inequalities in the exposome have been found to be complex and highly context-specific, but studies have not been conducted in large population-wide cohorts from multiple countries. This study aims to examine the external exposome, encompassing individual and environmental factors influencing health over the life course, and to perform dimension reduction to derive interpretable characterization of the external exposome for multicountry epidemiological studies. Analyzing data from over 25 million individuals across seven European countries including 12 administrative and traditional cohorts, we utilized domain-specific principal component analysis (PCA) to define the external exposome, focusing on air pollution, the built environment, and air temperature. We conducted linear regression to estimate the association between individual- and area-level socioeconomic position and each domain of the external exposome. Consistent exposure patterns were observed within countries, indicating the representativeness of traditional cohorts for air pollution and the built environment. However, cohorts with limited geographical coverage and Southern European countries displayed lower temperature variability, especially in the cold season, compared to Northern European countries and cohorts including a wide range of urban and rural areas. The individual- and area-level socioeconomic determinants (i.e., education, income, and unemployment rate) of the urban exposome exhibited significant variability across the European region, with area-level indicators showing stronger associations than individual variables. While the PCA approach facilitated common interpretations of the external exposome for air pollution and the built environment, it was less effective for air temperature. The diverse socioeconomic determinants suggest regional variations in environmental health inequities, emphasizing the need for targeted interventions across European countries.

Effect modification of air pollution on the association between heat and mortality in five European countries.

BACKGROUND: Evidence suggests that air pollution modifies the association between heat and mortality. However, most studies have been conducted in cities without rural data. This time-series study examined potential effect modification of particulate matter (PM) and ozone (O3) on heat-related mortality using small-area data from five European countries, and explored the influence of area characteristics. METHODS: We obtained daily non-accidental death counts from both urban and rural areas in Norway, England and Wales, Germany, Italy, and the Attica region of Greece during the warm season (2000-2018). Daily mean temperatures and air pollutant concentrations were estimated by spatial-temporal models. Heat effect modification by air pollution was assessed in each small area by over-dispersed Poisson regression models with a tensor smoother between temperature and air pollution. We extracted temperature-mortality relationships at the 5th (low), 50th (medium), and 95th (high) percentiles of pollutant distributions. At each air pollution level, we estimated heat-related mortality for a temperature increase from the 75th to the 99th percentile. We applied random-effects meta-analysis to derive the country-specific and overall associations, and mixed-effects meta-regression to examine the influence of urban-rural and coastal typologies and greenness on the heat effect modification by air pollution. RESULTS: Heat-related mortality risks increased with higher PM levels, rising by 6.4% (95% CI: -2.0%-15.7%), 10.7% (2.6%-19.5%), and 14.1% (4.4%-24.6%) at low, medium, and high PM levels, respectively. This effect modification was consistent in urban and rural regions but more pronounced in non-coastal regions. In addition, heat-mortality associations were slightly stronger at high O3 levels, particularly in regions with low greenness. CONCLUSION: Our analyses of both urban and rural data indicate that air pollution may intensify heat-related mortality, particularly in non-coastal and less green regions. The synergistic effect of heat and air pollution implies a potential pathway of reducing heat-related health impacts by improving air quality.

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study.

INTRODUCTION/OBJECTIVES: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation. METHODS: We analyzed data from 1,370 participants of the KORA FF4 study (Germany). Metabolites were measured by Metabolon, Inc. (untargeted) in stool, and using the AbsoluteIDQ® p180 kit (targeted) in blood. Multiple linear regression models, adjusted for dietary pattern, age, sex, physical activity, smoking status and alcohol intake, were used to estimate the associations of metabolites with the MetS, its components and high-sensitivity C-reactive protein (hsCRP) levels. Partial correlation and Multi-Omics Factor Analysis (MOFA) were used to investigate the relationship between stool and blood metabolites. RESULTS: The MetS was significantly associated with 170 stool and 82 blood metabolites. The MetS components with the highest number of associations were triglyceride levels (stool) and HDL levels (blood). Additionally, 107 and 27 MetS-associated metabolites (in stool and blood, respectively) showed significant associations with hsCRP levels. We found low partial correlation coefficients between stool and blood metabolites. MOFA did not detect shared variation across the two datasets. CONCLUSIONS: The MetS, particularly dyslipidemia, is associated with multiple stool and blood metabolites that are also associated with systemic inflammation. Further studies are necessary to validate our findings and to characterize metabolic alterations in the MetS. Although our analyses point to weak correlations between stool and blood metabolites, additional studies using integrative approaches are warranted.

Association between air temperature and self-perceived health status in Southern Germany: Results from KORA FIT study.

BACKGROUND: Short-term exposure to low and high air temperatures can cause serious harmful effects on human health. Existing literature has mostly focused on associations of ambient air temperature with mortality and the need for health care in population-level studies. Studies that have considered self-perceived health status as an outcome when examining the effects of air temperature on health are scarce. In this study, we explored the short-term association of daily mean air temperature with various measures of self-perceived health status. METHODS: This cross-sectional analysis is based on the Cooperative Health Research in the Region of Augsburg (KORA) FIT study conducted in 2018/2019 and included participants from the Augsburg region of Southern Germany. Health-related quality of life (HRQOL) was evaluated by using the 5-level EuroQol Five Dimension (EQ-5D-5L) questionnaire, including the EuroQol visual analog scale (EQ-VAS). Self-rated health (SRH) and comparative self-rated health (CSRH) were each assessed using a single question. Daily mean air temperature data was estimated using a spatiotemporal model and assigned to participants' home addresses at a resolution of 1 × 1 km. Regression models with a Distributed Lag Non-linear Modeling (DLNM) approach were used to investigate the associations between daily mean air temperature and self-perceived health measures. RESULTS: We found no association of heat or cold with the HRQOL, SRH or CSRH. Nevertheless, there was a significant protective association of low air temperature with the EQ-5D-5L dimension "usual activities." CONCLUSION: There was no evidence of daily mean air temperature adversely affecting participants' self-perceived health status.

Public attitudes towards personal health data sharing in long-term epidemiological research: a Citizen Science approach in the KORA study.

BACKGROUND: Loss to follow-up in long-term epidemiological studies is well-known and often substantial. Consequently, there is a risk of bias to the results. The motivation to take part in an epidemiological study can change over time, but the ways to minimize loss to follow-up are not well studied. The Citizen Science approach offers researchers to engage in direct discussions with study participants and to integrate their opinions and requirements into cohort management. METHODS: Guided group discussions were conducted with study participants from the KORA cohort in the Augsburg Region in Germany, established 40 years ago, as well as a group of independently selected citizens. The aim was to look at the relevant aspects of health studies with a focus on long-term participation. A two-sided questionnaire was developed subsequently in a co-creation process and presented to 500 KORA participants and 2,400 employees of the research facility Helmholtz Munich. RESULTS: The discussions revealed that altruistic motivations, (i.e. supporting research and public health), personal benefits (i.e. a health check-up during a study examination), data protection, and information about research results in layman's terms were crucial to ensure interest and long-term study participation. The results of the questionnaire confirmed these aspects and showed that exclusively digital information channels may be an obstacle for older and less educated people. Thus, paper-based media such as newsletters are still important. CONCLUSIONS: The findings shed light on cohort management and long-term engagement with study participants. A long-term health study needs to benefit public and individual health; the institution needs to be trustworthy; and the results and their impact need to be disseminated in widely understandable terms and by the right means of communication back to the participants.

Baseline MRI Examination in the NAKO Health Study­Findings on Feasibility, Participation and Dropout Rates, Comfort, and Image Quality.

BACKGROUND: Magnetic resonance imaging (MRI) yields important information on the development and current status of many different diseases. Whole-body MRI was accordingly made a part of the multicenter, population-based NAKO Health Study. The present analysis concerns the feasibility of the baseline MRI examination and various aspects of quality assurance over the period 2014-2019. METHODS: 32 252 participants in the NAKO Health Study, aged 20 to 74, who had no contraindication to MRI were invited to undergo scanning in one of five MRI study centers across Germany. The whole-body MRI scan took about one hour and consisted of sequences for the visualization of structural and functional features of the brain, musculoskeletal system, cardiovascular system, and thoracoabdominal system. A comprehensive quality-assurance assessment was carried out, with evaluation of adverse events, the completeness of the MRI protocols, the participants' subjective perceptions, and image quality. RESULTS: 31 578 participants (97.9%) were successfully included in the MRI study. They reported a high level of comfort and suffered no severe adverse events; mild adverse events occurred in only four participants. Depending on the imaging sequence, the image quality was rated as excellent in 80.2% to 96.8% of cases. Quality assessment with respect to structural features of the brain revealed high consistency across study centers, as well as with regard to age-and sex-based differences in brain volume (men, 1203.81 ± 102.06 cm³; women, 1068.10 ± 86.69 cm³). CONCLUSION: Whole-body MRI was successfully implemented in the NAKO baseline examination and was associated with high patient comfort and very good image quality. The imaging biomarkers of the brain confirmed previously observed differences based on age and sex, underscoring the feasibility of data pooling.