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Abstract A significant increase in circulating cell‐free DNA (cfDNA) occurs with physical exercise, which depends on the type of exertion and the duration. The aims of this study were as follows: (1) to investigate the time course of cfDNA and conventional markers of muscle damage from immediately after to 96 h after muscle‐damaging exercise; and (2) to investigate the relationship between cfDNA and indicators of primary (low‐frequency fatigue and maximal voluntary isometric contraction) and secondary (creatine kinase and delayed‐onset muscle soreness) muscle damage in young healthy males. Fourteen participants (age, 22 ± 2 years; weight, 84.4 ± 11.2 kg; height, 184.0 ± 7.4 cm) performed 50 intermittent drop jumps at 20 s intervals. We measured cfDNA and creatine kinase concentrations, maximal voluntary isometric contraction torque, low‐frequency fatigue and delayed‐onset muscle soreness before and at several time points up to 96 h after exercise. Plasma cfDNA levels increased from immediately postexercise until 72 h postexercise (P

BackgroundSocietal measures to contain the spread of COVID-19 (eg, lockdown and contact restrictions) have been associated with decreased health and well-being. A multitude of prepandemic studies identified the beneficial effects of physical exercise on both physical and mental health. ObjectiveWe report on the feasibility of a remote physical exercise intervention and its stress-buffering potential in 2 untrained cohorts: a pre–COVID-19 cohort that completed the intervention in 2019 and a lockdown cohort that started the intervention shortly before pandemic-related restrictions were implemented. MethodsIn a randomized controlled trial, participants were assigned to either an intervention group (IG; pre–COVID-19 cohort: n=7 and lockdown cohort: n=9) or a control group (CG; pre–COVID-19 cohort: n=6 and lockdown cohort: n=6). IG participants received weekly individualized training recommendations delivered via web-based support. The intervention period was initially planned for 8 weeks, which was adhered to in the pre–COVID-19 cohort (mean 8.3, SD 0.5 weeks) but was extended to an average of 17.7 (SD 2.0) weeks in the lockdown cohort. Participants’ health parameters were assessed before and after the intervention: aerobic capacity was measured as peak oxygen uptake (VO2peak) via cardiopulmonary exercise testing. Depressive symptoms were scored via the depression subscale of the Brief Symptom Inventory-18. ResultsDropout rates were low in both cohorts in the IG (pre–COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 16.7%) and the CG (pre–COVID-19 cohort: n=0, 0% and lockdown cohort: n=2, 20%). The mean adherence to the training sessions of the IG for both cohorts was 84% (pre–COVID-19 cohort: SD 5.5% and lockdown cohort: SD 11.6%). Aligned rank transform ANOVAs in the lockdown cohort indicated deterioration of VO2peak and depressive symptoms from before to after the intervention in the CG but no longitudinal changes in the IG. Analyses in the pre–COVID-19 cohort revealed significant increases in VO2peak for the IG compared to the CG (P=.04) but no intervention effects on depressive symptoms. ConclusionsWith low dropout rates and high adherence, the remote intervention was feasible for healthy adults under regular conditions and in the face of pandemic-related stressors. Moreover, our results hint at a stress-buffering effect as well as a buffering of a lockdown-induced deconditioning of remote physical exercise interventions in the pandemic scenario, which can be used in future studies to overcome equally stressful periods of life. However, due to limited statistical power, these findings should be replicated in similar scenarios. Trial RegistrationGerman Clinical Trials Register DRKS00018078; https://drks.de/search/en/trial/DRKS00018078

BackgroundThe transition from school to university is often accompanied by a change in students’ lifestyles. So far little is known whether convenience behavior is an essential factor affecting students’ health and social interaction. In a heterogeneous population regard to sociodemographic and anthropometric characteristics the Convenience Behavior Questionnaire (CBQ) showed a better relationship between convenience-related behavior with overweight and obesity than established questionnaires. Here we assessed convenience behavior in a large well characterized cohort of university students and its association with health-related (mainly sedentary behavior and physical activity), study-related and sociodemographic factors with the Convenience Behavior Questionnaire (CBQ).MethodsA total of 4,351 students participated in an online survey, of which 3,983 (23.6 ± 5.3 years old, 71.3% females) answered the questions concerning convenience behavior. A low value in the CBQ indicates more convenience behavior [Convenience Behavior Index (CBI) range: 3–15]. Differences with regard to sociodemographic (age, gender, body mass index), study-related (semester, degree, field of study) and health-related (physical activity, sedentary behavior) variables were examined with Mann–Whitney-U test or Kruskal–Wallis test and post-hoc tests (Bonferroni).ResultsThe CBI of men and women differed significantly (z = −6.847, p

This study examined the acute effects of exercise testing on immunology markers, established blood-based biomarkers, and questionnaires in endurance athletes, with a focus on biological sex differences. Twenty-four healthy endurance-trained participants (16 men, age: 29.2±7.6 years, maximal oxygen uptake (V̇ O 2max ): 59.4±7.5 ml·min −1 · kg −1 ; 8 women, age: 26.8±6.1 years, V̇ O 2max : 52.9±3.1 ml·min −1 · kg −1 ) completed an incremental submaximal exercise test and a ramp test. The study employed exploratory bioinformatics analysis: mixed ANOVA, k-means clustering, and uniform manifold approximation and projection, to assess the effects of exhaustive exercise on biomarkers and questionnaires. Significant increases in biomarkers (lymphocytes, platelets, procalcitonin, hemoglobin, hematocrit, red blood cells, cell-free DNA (cfDNA)) and fatigue were observed post-exercise. Furthermore, differences pre- to post-exercise were observed in cytokines, cfDNA, and other blood biomarkers between male and female participants. Three distinct groups of athletes with differing proportions of females (Cluster 1: 100% female, Cluster 2: 85% male, Cluster 3: 37.5% female and 65.5% male) were identified with k-means clustering. Specific biomarkers (e.g., interleukin-2 (IL-2), IL-10, and IL-13, as well as cfDNA) served as primary markers for each cluster, potentially informing individualized exercise responses. In conclusion, our study identified exercise-sensitive biomarkers and provides valuable insights into the relationships between biological sex and biomarker responses.

Abstract In 2011, a group of researchers investigated the 12-month prevalence of doping at the 13th International Association of Athletics Federations World Championships in Athletics (WCA) in Daegu, South Korea, and also at the 12th Pan-Arab Games (PAG) in Doha, Qatar. The prevalence of doping at each event was estimated using an established randomized response method, the Unrelated Question Model (UQM). The study, published in 2018, found that the prevalence of past-year doping was at least 30% at WCA and 45% at PAG. At both events, separate data sets were collected in addition to the UQM data using a new method, the single sample count (SSC). Recently, Petróczi et al. have reported 12-month doping prevalence estimates for these two events based on the SSC data. These investigators obtained substantially lower prevalence estimates using the SSC and suggested that the 2018 estimates based on the UQM may have been too high. However, in this communication, we point out several possible shortcomings in the methods of Petróczi et al. and show that their SSC data would be equally compatible with a high 12-month doping prevalence comparable to the UQM estimates published in 2018.

Abstract Background Extracellular vesicles (EVs) originating from the central nervous system (CNS) can enter the blood stream and carry molecules characteristic of disease states. Therefore, circulating CNS-derived EVs have the potential to serve as liquid-biopsy markers for early diagnosis and follow-up of neurodegenerative diseases and brain tumors. Monitoring and profiling of CNS-derived EVs using multiparametric analysis would be a major advance for biomarker as well as basic research. Here, we explored the performance of a multiplex bead-based flow-cytometry assay (EV Neuro) for semi-quantitative detection of CNS-derived EVs in body fluids. Methods EVs were separated from culture of glioblastoma cell lines (LN18, LN229, NCH82) and primary human astrocytes and measured at different input amounts in the MACSPlex EV Kit Neuro, human. In addition, EVs were separated from blood samples of small cohorts of glioblastoma (GB), multiple sclerosis (MS) and Alzheimer’s disease patients as well as healthy controls (HC) and subjected to the EV Neuro assay. To determine statistically significant differences between relative marker signal intensities, an unpaired samples t-test or Wilcoxon rank sum test were computed. Data were subjected to tSNE, heatmap clustering, and correlation analysis to further explore the relationships between disease state and EV Neuro data. Results Glioblastoma cell lines and primary human astrocytes showed distinct EV profiles. Signal intensities were increasing with higher EV input. Data normalization improved identification of markers that deviate from a common profile. Overall, patient blood-derived EV marker profiles were constant, but individual EV populations were significantly increased in disease compared to healthy controls, e.g. CD36+EVs in glioblastoma and GALC+EVs in multiple sclerosis. tSNE and heatmap clustering analysis separated GB patients from HC, but not MS patients from HC. Correlation analysis revealed a potential association of CD107a+EVs with neurofilament levels in blood of MS patients and HC. Conclusions The semi-quantitative EV Neuro assay demonstrated its utility for EV profiling in complex samples. However, reliable statistical results in biomarker studies require large sample cohorts and high effect sizes. Nonetheless, this exploratory trial confirmed the feasibility of discovering EV-associated biomarkers and monitoring circulating EV profiles in CNS diseases using the EV Neuro assay. Video Abstract

Background COVID-19 is a worldwide pandemic caused by the highly infective SARS-CoV-2. There is a need for biomarkers not only for overall prognosis but also for predicting the response to treatments and thus for improvements in the clinical management of patients with COVID-19. Circulating cell-free DNA (cfDNA) has emerged as a promising biomarker in the assessment of various pathological conditions. The aim of this retrospective and observational pilot study was to investigate the range of cfDNA plasma concentrations in hospitalized COVID-19 patients during the first wave of SARS-CoV-2 infection, to relate them to established inflammatory parameters as a correlative biomarker for disease severity, and to compare them with plasma levels in a healthy control group. Methods Lithium-Heparin plasma samples were obtained from COVID-19 patients (n = 21) during hospitalization in the University Medical Centre of Mainz, Germany between March and June 2020, and the cfDNA concentrations were determined by quantitative PCR yielding amplicons of long interspersed nuclear elements (LINE-1). The cfDNA levels were compared with those of an uninfected control group (n = 19). Results Plasma cfDNA levels in COVID-19 patients ranged from 247.5 to 6,346.25 ng/ml and the mean concentration was 1,831 ± 1,388 ng/ml (± standard deviation), which was significantly different from the levels of the uninfected control group (p < 0.001). Regarding clinical complications, the highest correlation was found between cfDNA levels and the myositis (p = 0.049). In addition, cfDNA levels correlated with the “WHO clinical progression scale”. D-Dimer and C-reactive protein (CRP) were the clinical laboratory parameters with the highest correlations with cfDNA levels. Conclusion The results of this observational pilot study show a wide range in cfDNA plasma concentrations in patients with COVID-19 during the first wave of infection and confirm that cfDNA plasma concentrations serve as a predictive biomarker of disease severity in COVID-19.

Abstract Background Impaired respiratory and intestinal microbiome composition is linked to cystic fibrosis lung disease severity. In people with cystic fibrosis (pwCF), regular exercise is recommended to delay disease progression and preserve a stable lung function. An optimal nutritional status is vital for best clinical outcomes. Our study investigated whether regular and monitored exercise and nutritional support promotes CF microbiome health. Methods A personalized nutrition and exercise program promoted nutritional intake and physical fitness in 18 pwCF for 12 months. Throughout the study, patients performed strength and endurance training monitored by a sports scientist via an internet platform. After three months, food supplementation with Lactobacillus rhamnosus LGG was introduced. Nutritional status and physical fitness were assessed before the study started, after three and nine months. Sputum and stool were collected, and microbial composition was analyzed by 16S rRNA gene sequencing. Results Sputum and stool microbiome composition remained stable and highly specific to each patient during the study period. Disease-associated pathogens dominated sputum composition. Lung disease severity and recent antibiotic treatment had the highest impact on taxonomic composition in stool and sputum microbiome. Strikingly, the long-term antibiotic treatment burden had only a minor influence. Conclusion Despite the exercise and nutritional intervention, respiratory and intestinal microbiomes proved to be resilient. Dominant pathogens drove the composition and functionality of the microbiome. Further studies are required to understand which therapy could destabilize the dominant disease-associated microbial composition of pwCF.

Abstract Background As circulating DNA (cirDNA) is mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood, apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNA. Methods We studied (1) the in vitro kinetics of cell derived genomic high molecular weight (gHMW) DNA degradation in serum; (2) the production of extracellular DNA and NET markers such as neutrophil elastase (NE) and myeloperoxidase (MPO) by ex vivo activated neutrophils; and (3) the in vitro NET degradation in serum; for this, we exploited the synergistic analytical information provided by specifically quantifying DNA by qPCR, and used shallow WGS and capillary electrophoresis to perform fragment size analysis. We also performed an in vivo study in knockout mice, and an in vitro study of gHMW DNA degradation, to elucidate the role of NE and MPO in effecting DNA degradation and fragmentation. We then compared the NET-associated markers and fragmentation size profiles of cirDNA in plasma obtained from patients with inflammatory diseases found to be associated with NET formation and high levels of cirDNA (COVID-19, N = 28; systemic lupus erythematosus, N = 10; metastatic colorectal cancer, N = 10; and from healthy individuals, N = 114). Results Our studies reveal that gHMW DNA degradation in serum results in the accumulation of mono-N DNA (81.3% of the remaining DNA following 24 h incubation in serum corresponded to mono-N DNA); “ex vivo” NET formation, as demonstrated by a concurrent 5-, 5-, and 35-fold increase of NE, MPO, and cell-free DNA (cfDNA) concentration in PMA-activated neutrophil culture supernatant, leads to the release of high molecular weight DNA that degrades down to mono-N in serum; NET mainly in the form of gHMW DNA generate mono-N cirDNA (2 and 41% of the remaining DNA after 2 h in serum corresponded to 1–10 kbp fragments and mono-N, respectively) independent of any cellular process when degraded in serum; NE and MPO may contribute synergistically to NET autocatabolism, resulting in a 25-fold decrease in total DNA concentration and a DNA fragment size profile similar to that observed from cirDNA following 8 h incubation with both NE and MPO; the cirDNA size profile of NE KO mice significantly differed from that of the WT, suggesting NE involvement in DNA degradation; and a significant increase in the levels of NE, MPO, and cirDNA was detected in plasma samples from lupus, COVID-19, and mCRC, showing a high correlation with these inflammatory diseases, while no correlation of NE and MPO with cirDNA was found in HI. Conclusions Our work describes the mechanisms by which NET and cirDNA are linked. In doing so, we demonstrate that NET are a major source of mono-N cirDNA independent of apoptosis and establish a new paradigm of the mechanisms of cirDNA release in normal and pathological conditions. We also demonstrate a link between immune response and cirDNA.

Abstract Vaccination hesitancy has been a major challenge for health authorities and societies during the COVID-19 pandemic. The general determinants of vaccination intentions and behavior include sociodemographic and health-related, psychological, and communication-related factors, with varying relevance for different types of vaccinations, countries, and target groups. The predictors of university students’ COVID-19 vaccination behavior have not been sufficiently studied. Using a German university as an example and based on an online survey of 1398 university students, we investigated factors related to (a) the likelihood of vaccination against COVID-19 and (b) vaccination intention among those who had not been vaccinated by summer of 2021. Psychological factors showed high relevance. Field of study, trust in, and use of certain media and information channels were found to be important determinants of students’ vaccination decision. Our findings can help better understand university students’ vaccination behavior to develop and implement tailored strategies and campaigns.

BackgroundSedentary behavior (SB) is highly prevalent among university students and has increased during COVID-19 pandemic. As SB is associated with negative health outcomes, appropriate prevention measures in the university setting are needed.ObjectiveThis pilot study aimed at investigating the effects of videos using different message strategies to interrupt SB in the collective of university students during online lectures.MethodsDuring online lectures, university students (N = 96) were shown one of three videos on the interruption of SB. The videos differed in their message strategies with regard to evidence type (statistical vs. narrative) and vividness (static vs. animated images). Demographics, health variables (SB intentions, SB attitudes) and selected media reception variables (identification, homophily, counterarguing) were examined as possible influence factors on the interruption of SB evoked by watching the video.ResultsApproximately half of the students interrupted sedentary behavior during watching the videos and students of the older age group (cut-off: median = 22 years) interrupted SB significantly more often (p = 0.046). The interruption of SB was predicted by SB intentions (p

(1) Background: Cigarette smoking, risky alcohol consumption, and marijuana smoking are the most common behaviors related to legal and illicit drug use worldwide, including among university students. To plan effective evidence-based programs to prevent the risky consumption of these substances among university students, the present study aimed to identify potential sociodemographic and study-related risk groups and predictors of consumption. (2) Methods: A cross-sectional online health survey with approximately 270 health-related items was conducted among students at the University of Mainz, Germany. Cigarette smoking, risky alcohol consumption (AUDIT-C score: female ≥ 4, male ≥ 5), and marijuana smoking were chosen as dependent variables. Of the 270 health-related items, 56 were chosen as independent variables and collated into five groups (sociodemographic, psychological, study-related psychosocial, general psychosocial and health behavior). The prevalence of cigarette smoking, risky alcohol consumption, and marijuana smoking was assessed using established and validated instruments. Pearson’s chi-square test was used to analyze the differences in prevalence between the sociodemographic and study-related groups, and binary logistic regression was used for analyses with stepwise inclusion of the five variable groups. (3) Results: Of the 3991 university students who entered the analyses, 14.9% reported smoking cigarettes, 38.6% reported risky alcohol consumption, and 10.9% reported smoking marijuana. The prevalence of these differed between genders, fields of study, and aspired degree level, among other factors. Binary logistic regression analyses revealed nine significant predictors (p ≤ 0.05) of cigarette smoking (Nagelkerke R2 = 0.314), 18 significant predictors of risky alcohol consumption (Nagelkerke R2 = 0.270), and 16 significant predictors of marijuana smoking (Nagelkerke R2 = 0.239). (4) Conclusions: This study showed cigarette smoking, risky alcohol consumption, and marijuana smoking among university students in Germany to be associated with multiple factors, especially health behaviors. Furthermore, each of the substances was highly associated with each of the two other substances we examined. Other variable groups, such as psychological or psychosocial variables, seemed to play a rather minor role. Therefore, our recommendation for future prevention programs is that substance use among university students should be addressed as a whole, not just in terms of specific substances.

BackgroundThe present study aimed to (1) assess and compare sedentary time (ST) of university students before and during the COVID-19 pandemic, (2) examine risk groups with regard to ST and the “extent of change” in ST (from before to during the pandemic) in association with sociodemographic (gender, age), study-related (degree aspired to, field of study, semester), and pre-pandemic physical health-related [pre-pandemic physical activity (PA) and ST levels, pre-pandemic BMI class] variables, and (3) investigate whether the change in ST was predicted by these variables.MethodsTwo online surveys were conducted among students at the University of Mainz, Germany—the first in 2019 (before the pandemic) and the second in 2020 (during the pandemic). Participants of both surveys were included in a longitudinal sample. With the longitudinal sample's data, paired t-tests, single factor, and mixed analyses of variances were used to examine group differences in ST and the “extent of change” in ST. A linear regression analysis was computed to investigate the influence of the abovementioned sociodemographic, study-related, and pre-pandemic physical health-related variables on the change in ST.ResultsOf the N = 4,351 (pre-pandemic) and N = 3,066 (in-pandemic) participants of the online surveys, N = 443 entered the longitudinal sample. ST increased by 1.4 h/day to critical levels (≥8 h/day) in all subgroups analyzed—even among students who were highly physically active before the pandemic. Students with a low pre-pandemic ST had the largest increase in ST. Pre-pandemic PA level negatively predicted the change in ST.ConclusionEven during a global pandemic lockdown, individuals who were previously more physically active and had less ST showed more health-promoting behavior in terms of ST. Therefore, it can be stated that efforts to promote PA and reduce ST are always valuable. Since ST increased and was worryingly high in all subgroups analyzed, all university students should be targeted by multidimensional approaches to tackle ST and promote their health.

Abstract Background Performing multiple high-intensity interval training (HIIT) sessions in a compressed period of time (approximately 7–14 days) is called a HIIT shock microcycle (SM) and promises a rapid increase in endurance performance. However, the efficacy of HIIT-SM, as well as knowledge about optimal training volumes during a SM in the endurance-trained population have not been adequately investigated. This study aims to examine the effects of two different types of HIIT-SM (with or without additional low-intensity training (LIT)) compared to a control group (CG) on key endurance performance variables. Moreover, participants are closely monitored for stress, fatigue, recovery, and sleep before, during and after the intervention using innovative biomarkers, questionnaires, and wearable devices. Methods This is a study protocol of a randomized controlled trial that includes the results of a pilot participant. Thirty-six endurance trained athletes will be recruited and randomly assigned to either a HIIT-SM (HSM) group, HIIT-SM with additional LIT (HSM + LIT) group or a CG. All participants will be monitored before (9 days), during (7 days), and after (14 days) a 7-day intervention, for a total of 30 days. Participants in both intervention groups will complete 10 HIIT sessions over 7 consecutive days, with an additional 30 min of LIT in the HSM + LIT group. HIIT sessions consist of aerobic HIIT, i.e., 5 × 4 min at 90–95% of maximal heart rate interspersed by recovery periods of 2.5 min. To determine the effects of the intervention, physiological exercise testing, and a 5 km time trial will be conducted before and after the intervention. Results The feasibility study indicates good adherence and performance improvement of the pilot participant. Load monitoring tools, i.e., biomarkers and questionnaires showed increased values during the intervention period, indicating sensitive variables. Conclusion This study will be the first to examine the effects of different total training volumes of HIIT-SM, especially the combination of LIT and HIIT in the HSM + LIT group. In addition, different assessments to monitor the athletes' load during such an exhaustive training period will allow the identification of load monitoring tools such as innovative biomarkers, questionnaires, and wearable technology. Trial Registration: clinicaltrials.gov, NCT05067426. Registered 05 October 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05067426 . Protocol Version Issue date: 1 Dec 2021. Original protocol. Authors: TLS, NH.

Abstract Aiming to develop and implement intervention strategies targeting pharmacological neuroenhancement (PN) among university students more specifically, we (1) assessed the prevalence of PN among German university students, (2) identified potential sociodemographic and study-related risk groups, and (3) investigated sociodemographic, psychological, study-related psychosocial, general psychosocial and health behavior related factors predicting the 12-month prevalence of PN. Therefore, a cross-sectional online survey was administered to students of the University of Mainz, Germany. A binary logistic regression with stepwise inclusion of the five variable groups was performed to predict PN. A total number of 4351 students out of 31,213 registered students (13.9%) participated in the survey, of which N = 3984 answered the question concerning PN. Of these, 10.4% had used one substance for PN at least once in the past 12 months. The regression analysis revealed 13 variables that were significantly related to the 12-month prevalence of PN. Specifically, the group of health behavior related variables showed the strongest relationship with PN. Therefore, an approach to the prevention of PN should be multifactorial so that it addresses social conditions, as well as education on substance use and healthy behaviors in terms of non-pharmacological strategies as alternatives of PN.

Load management, i.e., prescribing, monitoring, and adjusting training load, is primarily aimed at preventing injury and maximizing performance. The search for objective monitoring tools to assess the external and internal load of athletes is of great interest for sports science research. In this 4-week pilot study, we assessed the feasibility and acceptance of an extensive monitoring approach using biomarkers, neuromuscular performance, and questionnaires in an elite youth soccer setting. Eight male players (mean ± SD: age: 17.0 ± 0.6 years, weight: 69.6 ± 8.2 kg, height: 177 ± 7 cm, VO2max: 62.2 ± 3.8 ml/min/kg) were monitored with a local positioning system (e.g., distance covered, sprints), biomarkers (cell-free DNA, creatine kinase), questionnaires, neuromuscular performance testing (counter-movement jump) and further strength testing (Nordic hamstring exercise, hip abduction and adduction). Feasibility was high with no substantial impact on the training routine and no adverse events such as injuries during monitoring. Adherence to the performance tests was high, but adherence to the daily questionnaires was low, and decreased across the study period. Occasional significant correlations were observed between questionnaire scores and training load data, as well as between questionnaire scores and neuromuscular performance. However, due to the small sample size, these findings should be treated with caution. These preliminary results highlight the feasibility of the approach in elite soccer, but also indicate that modifications are needed in further large-scale studies, particularly in relation to the length of the questionnaire.

Abstract Background Regular participation in exercise is important for people with cystic fibrosis (CF). Therefore, we implemented a personalized, web-based exercise intervention over the course of one year for people with CF. The aims were to investigate the feasibility of the intervention and to evaluate changes in exercise participation, lung function, and exercise capacity. Methods In total, 11/17 participants [aged 12–52 years; FEV1%pred. 72.3 (SD: 17.3)] were included in the final data analysis. Every week, the participants received an individual training recommendation at the start and uploaded their training report on our website at the end of each week. The number of training minutes and sessions performed were analyzed over 13 four-week training sections. The participation in exercise (physical activity questionnaire), lung function and exercise capacity were assessed at baseline (T0), after 12 weeks (T1) and after 52 weeks (T2). Results A training duration of 178 min (SD: 75.5) and 3.3 (SD: 0.89) training sessions could be achieved weekly. In the first four-week training section, the participants performed 137.31 (SD: 95.7) minutes of training, with an increase of 42% in the third training section (195.01, SD: 134.99). Minutes of training reported on the questionnaire increased by 39.7% from T0 (179.38 min, SD: 120.9) to T1 (250.63 min, SD: 124.1) but decreased at T2 (166.88, SD: 155.4). There were slight decreases in lung function (FEV1 − 3.9%pred.; FVC − 1.9%pred.) and slight increases in exercise capacity (VO2peak + 1.5 ml/min/kg; six-minute-walk-test-distance + 26 m). Noticeably, five participants experienced deteriorations in their FEV1 of more than 5% but simultaneously experienced improvements in the parameters of exercise capacity of more than 5% throughout the year. Conclusions The web-based concept was feasible for the participants over the course of a year and supported exercise participation. The improvement in exercise capacity due to increased exercise participation over a prolonged period of time, despite a decrease in lung function, should be further investigated. Finally, if integrated into usual care, this approach could facilitate the prescription of regular personalized exercise and promote exercise participation in the daily lives of people with CF.

Abstract Circulating cell-free DNA (cfDNA) has been investigated as a screening tool for many diseases. To avoid expensive and time-consuming DNA isolation, direct quantification PCR assays can be established. However, rigorous validation is required to provide reliable data in the clinical and non-clinical context. Considering the International Organization for Standardization, as well as bioanalytical method validation guidelines, we provide a comprehensive procedure to validate assays for cfDNA quantification from blood plasma without DNA isolation. A 90 and 222 bp assay was validated to study the kinetics of cfDNA after exercise in patients with systemic lupus erythematosus (SLE). The assays showed ultra-low limit of quantification (LOQ) with 0.47 and 0.69 ng/ml, repeatability ≤ 11.6% (95% CI 8.1–20.3), and intermediate precision ≤ 12.1% (95% CI 9.2–17.7). Incurred sample reanalysis confirmed the precision of the procedure. The additional consideration of pre-analytical factors shows that centrifugation speed and temperature do not change cfDNA concentrations. In SLE patients cfDNA increases ~ twofold after a walking exercise, normalizing after 60 min of rest. The established assays allow reliable and cost-efficient quantification of cfDNA in minute amounts of plasma in the clinical setting. Additionally, the assay can be used as a tool to determine the impact of pre-analytical factors and validate cfDNA quantity and quality of isolated samples.

BackgroundPhysical inactivity and sedentary behavior are modifiable risk factors for an unhealthy lifestyle in university students. The aim of this study was to identify subgroups among German university students with an increased risk for unhealthy behavior. For this purpose, differences in physical activity and sedentary behavior with respect to sociodemographic and study related factors were examined.MethodsA total of 4,351 students participated in an online survey. The amount of physical activity (metabolic equivalent of task-min/week) and the sitting time (h/day) were assessed using the German short form of the International Physical Activity Questionnaire. Differences in gender and age as well as field of study, targeted degree and study semester were analyzed using a single factorial ANOVA with Tukey correction or a Welch-ANOVA with Games-Howell correction.ResultsFor physical activity, significant differences were found for gender (F(2, 80.46) = 17.79, p < 0.001, ηp2 = 0.009), for field of study (F(5, 1738.09) = 7.41, p < 0.001, ηp2 = 0.01), and for study semester (F(1, 948.12) = 5.53, p < 0.05, ηp2 =0.001), but not for age and targeted degree (p > 0.05). For sedentary behavior, significant differences were found for field of study (F(5, 3816) = 5.69, p < 0.001, ηp2 = 0.01) and targeted degree (F(3, 3868) = 3.94, p < 0.01, ηp2 = 0.003), but not for gender, age and study semester (p > 0.05).ConclusionFemale students, students enrolled in “natural sciences, mathematics and informatics” and first year students appear to have an increased risk of an unhealthy lifestyle. Future research should identify barriers to and incentives of physical activity as well as reasons for high amounts of SB in sub-populations of university students. Suitable prevention and intervention programs are necessary.

Job crafting has been established as a bottom-up work design instrument for promoting health and well-being in the workplace. In recent years, the concepts of job crafting have been applied to the university student context, proving to be positively related to student well-being. Building on person-centered analyses from the employment context, we assessed approach study crafting strategy combinations and the relationships to students’ exhaustion, study engagement, and general well-being. Data from 2,882 German university students were examined, collected online during the summer term in 2020. Using latent profile analysis, we found five distinct crafting groups, which showed discriminate validity with regard to emotional exhaustion, engagement, and well-being. The results underscore the positive role of study crafting for students’ health and well-being. They further indicate a less important role of increasing social resources for emotional exhaustion when combined with a moderate increase in structural resources and a moderate increase in challenging demands. Our findings imply that interventions to promote study crafting should be considered to promote student health and well-being.

Obstructive sleep apnea (OSA) has been associated with various acute and chronic inflammatory diseases, as has serum ferritin, an intracellular iron storage protein. Little is known about the relationship between severity of OSA and serum ferritin levels in otherwise healthy subjects. In this study, all polysomnographic recordings, serum levels of ferritin, C-reactive protein (CRP), and hemoglobin, as well as patient files from 90 consecutive, otherwise healthy individuals with suspected OSA who presented to a tertiary sleep medical center were retrospectively analyzed. For comparison, three groups were formed based on apnea–hypopnea index (AHI; none or mild OSA: 30/h). Serum ferritin levels were significantly positively correlated with AHI (r = 0.3240, p = 0.0020). A clear trend of higher serum ferritin levels was found when patients with severe OSA were compared to those without or with mild OSA. Serum CRP and serum hemoglobin levels did not differ significantly among OSA severity groups. Age and body–mass index (BMI) tended to be higher with increasing OSA severity. The BMI was significant higher in patients with severe OSA compared to those without or with mild (p < 0.001). Therefore, serum ferritin levels may provide a biochemical surrogate marker for OSA severity.

Background: Cancer-related fatigue (CRF) is one of the most common and distressing symptoms in paediatric oncology. Based on previous studies, physical activity interventions are considered to be effective in reducing CRF in adult cancer patients. Aim: The aim of this systematic review is to investigate whether physical activity interventions can reduce CRF in paediatric patients undergoing cancer treatment. Methodology: A systematic literature search was conducted in PubMed and Sport-Discus in October 2021 to identify intervention studies examining the effects of physical activity on CRF in cancer patients ≤ 21 years of age. Their methodological quality was assessed using the JBI Critical Appraisal Tool. Results: A total of 20 studies (seven randomized-controlled, six quasi-experimental and seven single-arm intervention trials) were included in the review. Nine studies reported significant positive effects of physical activity interventions on CRF in group comparison or within groups. Eleven trials reported no significant changes in CRF. Conclusion: Physical activity as a therapeutic intervention in paediatric oncology may have the potential to reduce CRF in childhood cancer patients undergoing cancer treatment. Further high-quality studies with large samples are needed to verify these results and to assess the interdependence of dose and response of physical activity interventions.

BackgroundAccording to the literature, the conditions of studying and living as well as the psychological, social and health behavior-related variables, which were strongly related to pharmacological neuroenhancement (PN) before the pandemic, significantly changed during the pandemic. For this reason, it is expected that the prevalence of PN among university students is higher during the pandemic compared to before the pandemic. Therefore, the present study aimed to investigate and compare the prevalence of PN among university students before and during the COVID-19-pandemic.MethodsThree online surveys assessing the 12-month prevalence of PN were conducted among university students at the University of Mainz, Germany. The first survey took place in summer term 2019 (before the pandemic), the second in summer term 2020 (during the first German lockdown), and the third in summer term 2021 (after the second German lockdown). Pearson's chi-square test was used to test whether the 12-month prevalence of PN differed significantly between the three surveys.ResultsThe 12-month prevalence of PN was 10.4% in 2019, 11.3% in 2020, and 8.0% in 2021. Chi-square tests revealed no statistical difference in the prevalence of PN between 2019 and 2020. Overall, the use of PN was lower in 2021 compared to 2019 (p < 0.0001) as well as in comparison to 2020 (p = 0.001). Only the use of cannabis slightly increased from 2019 to 2020 (7.1 vs. 8.3%) and decreased in 2021 (5.4%). At all three time points, cannabis was the most commonly used substance for the purpose of PN. Consequently, the results suggest that the prevalence of PN was highly intertwined with the prevalence of cannabis use for PN.DiscussionThe decrease in the prevalence of PN of around three percentage points in 2021 compared to the previous years was a surprising finding. It may be mainly due to the decrease in the prevalence of cannabis for the purpose of PN. However, the fairly high prevalence of PN of around 8% in 2021 is still an important finding that demonstrates that there is still an urgent need for prevention initiatives among university students to combat the use of PN.

Abstract Background Both glaucoma and obstructive sleep apnea (OSA) are widespread diseases. OSA may presumably partly cause or worsen glaucoma, although the etiopathogenesis is unclear. Here we analyze for the first time the possible association between different glaucoma phenotypes and OSA. Methods 110 patients (47 females, 63 males; median age 64.3 years, median BMI 26.62 kg/m2) with suspected glaucoma and without any prior diagnosis of OSA were prospectively studied by one-night home sleep apnea testing (HSAT), 101 of the patients were analyzed. HSAT parameters, like apnea hypopnea index (AHI) and oxygen desaturation index as well as opthalmological parameters like intraocular pressure (IOP) and mean defect depth (MD) were collected. Moreover, HSAT results were compared across four phenotypic groups: primary open angle glaucoma (POAG), low-tension-glaucoma (LTG), ocular hypertension (OH), and controls. Results There was no strong correlation between IOP or MD and AHI. BMI, age and gender did not differ between groups. Significant differences between POAG and LTG were found for all HSAT parameters. The AHI showed the most prominent group difference (Wilcoxon-Kruskal-Wallis rank sum test was highly significant with chi2 = 22, df = 3 p

Abstract Background The aim of the current study was to examine the relationship between anthropometric characteristics (i.e. body height, body weight, body mass index [BMI] and waist circumference [WC]) with motor performance ability [MPA], social environmental factors of the district (i.e. employment status/working life, education, social situation/heterogeneity and home environment), where the respective kindergarten was located, as well as other potential health determinants in a representative sample of kindergartners. Methods We analyzed data of 434 children aged 3 to 6 years which were obtained from a community-based cross-sectional health study conducted in the city of Mainz, Germany. Body height and weight, BMI and WC standard deviation scores [SDS] were calculated relative to the international proposed cut-offs of the IOTF. MPA was collected with multiple test items to determine coordination, speed strength, muscular endurance and speed. The life situation index [LSI] was used to assess the social environment of the district of the kindergarten. Adjusted for covariates, correlation and logistic regression analyses were conducted to estimate the effect of WC on MPA. Results Below-average MPA was found in 46% of the sample. While there was no relationship to BMI (odds ratio [OR]: 1.09, 95% confidence interval [95% CI]: 0.83–1.44; p = 0.538), WC SDS was positively associated with below-average MPA (OR: 1.41, 95% CI: 1.01–1.95; p = 0.041). Further results show that the social environment of the district of the kindergarten was independently related to below-average MPA (OR: 2.72, 95% CI: 1.29–5.75; p = 0.009). Conclusion The findings suggest that WC rather than BMI is linked to measurements of MPA already in kindergartners and furthermore, there seems to be an independent association between MPA and the social environment of the district of the respective kindergarten.

Patients with sleep-disordered breathing show a combination of different respiratory events (central, obstructive, mixed), with one type being predominant. We observed a reduced prevalence of central apneic events (CAEs) during REM sleep compared to NREM sleep in patients with predominant obstructive sleep apnea (OSA). The aim of this retrospective, exploratory study was to describe this finding and to suggest pathophysiological explanations. The polysomnography (PSG) data of 141 OSA patients were assessed for the prevalence of CAEs during REM and NREM sleep. On the basis of the apnea–hypopnea index (AHI), patients were divided into three OSA severity groups (mild: AHI < 15/h; moderate: AHI = 15–30/h; severe: AHI > 30/h). We compared the frequency of CAEs adjusted for the relative length of REM and NREM sleep time, and a significantly increased frequency of CAEs in NREM was found only in severely affected OSA patients. Given that the emergence of CAEs is strongly associated with the chemosensitivity of the brainstem nuclei regulating breathing mechanics in humans, a sleep-stage-dependent chemosensitivity is proposed. REM-sleep-associated neuronal circuits in humans may act protectively against the emergence of CAEs, possibly by reducing chemosensitivity. On the contrary, a significant increase in the chemosensitivity of the brainstem nuclei during NREM sleep is suggested.

Psychological stress affects the immune system and activates peripheral inflammatory pathways. Circulating cell-free DNA (cfDNA) is associated with systemic inflammation, and recent research indicates that cfDNA is an inflammatory marker that is sensitive to psychological stress in humans. The present study investigated the effects of acute stress on the kinetics of cfDNA in a within-subjects design. Twenty-nine males (mean age: 24.34 ± 4.08 years) underwent both the Trier Social Stress Test (TSST) and a resting condition. Blood samples were collected at two time points before and at 9 time points up to 105 min after both conditions. The cfDNA immediately increased 2-fold after the TSST and returned to baseline levels after 30 min after the test, showing that a brief psychological stressor was sufficient to evoke a robust and rapid increase in cfDNA levels. No associations were detected between perceived stress, whereas subjects with higher basal cfDNA levels showed higher increases. The rapid cfDNA regulation might be attributed to the transient activation of immune cells caused by neuroendocrine-immune activation. Further research is required to evaluate the reliability of cfDNA as a marker of neuroendocrine-immune activation, which could be used for diagnostics purposes or monitoring of treatment progression.

BackgroundPhysical activity alleviates chronic stress. The latest research suggests a relationship between resilience and physical fitness. Beneficial adaptations of the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, endocannabinoid system, and tryptophan pathway, which are induced by an active lifestyle, are considered to be conducive to resilience. However, detailed knowledge on the molecular link between the effects of acute and chronic physical exercise and improved resilience to stress in humans is missing. Moreover, the relationship between innate and acquired aerobic capacity and resilience is poorly understood. ObjectiveThe aim of this study is to implement a human exercise intervention trial addressing the following main hypotheses: a high innate aerobic capacity is associated with high resilience to stress, and web-based physical exercise training improves aerobic capacity of physically inactive adults, which is accompanied by improved resilience. In this setting, we will analyze the relationship between resilience parameters and innate and acquired aerobic capacity as well as circulating signaling molecules. MethodsA total of 70 healthy, physically inactive (

Sports-related pain and injury is directly linked to tissue inflammation, thus involving the autonomic nervous system (ANS). In the present experimental study, we disable the sympathetic part of the ANS by applying a stellate ganglion block (SGB) in an experimental model of delayed onset muscle soreness (DOMS) of the biceps muscle. We included 45 healthy participants (female 11, male 34, age 24.16 ± 6.67 years [range 18–53], BMI 23.22 ± 2.09 kg/m2) who were equally randomized to receive either (i) an SGB prior to exercise-induced DOMS (preventive), (ii) sham intervention in addition to DOMS (control/sham), or (iii) SGB after the induction of DOMS (rehabilitative). The aim of the study was to determine whether and to what extent sympathetically maintained pain (SMP) is involved in DOMS processing. Focusing on the muscular area with the greatest eccentric load (biceps distal fifth), a significant time × group interaction on the pressure pain threshold was observed between preventive SGB and sham (p = 0.034). There was a significant effect on pain at motion (p = 0.048), with post hoc statistical difference at 48 h (preventive SGB Δ1.09 ± 0.82 cm VAS vs. sham Δ2.05 ± 1.51 cm VAS; p = 0.04). DOMS mediated an increase in venous cfDNA -as a potential molecular/inflammatory marker of DOMS- within the first 24 h after eccentric exercise (time effect p = 0.018), with a peak at 20 and 60 min. After 60 min, cfDNA levels were significantly decreased comparing preventive SGB to sham (unpaired t-test p = 0.008). At both times, 20 and 60 min, cfDNA significantly correlated with observed changes in PPT. The 20-min increase was more sensitive, as it tended toward significance at 48 h (r = 0.44; p = 0.1) and predicted the early decrease of PPT following preventive stellate blocks at 24 h (r = 0.53; p = 0.04). Our study reveals the broad impact of the ANS on DOMS and exercise-induced pain. For the first time, we have obtained insights into the sympathetic regulation of pain and inflammation following exercise overload. As this study is of a translational pilot character, further research is encouraged to confirm and specify our observations.

The link between obstructive sleep apnea (OSA) and obesity, and their common comorbidities such as diabetes mellitus (DM) or cardiovascular diseases, is not fully understood. The aim of this study was to investigate the possible association of OSA severity in obese individuals with polysomnography-based sleep parameters, as well as C-reactive protein (CRP) and glycated hemoglobin (HbA1c) serum levels. Polysomnographic recordings and blood samples were retrospectively compared between a group of 23 adult obese individuals with mild OSA (apnea–hypopnea index (AHI) = 7.5 (5.5–12.5)/h, age = 42.57 ± 11.44 years, 16 male, 7 female, body mass index (BMI) = 37.35 ± 3.88 kg/m2) and an age-, sex-, and BMI-matched group of individuals with moderate or severe OSA (AHI 41.5 (25.7–71.8)/h, age = 43.43 ± 11.96 years, 16 male, 7 female, BMI = 37.87 ± 4.74 kg/m2). All respiratory sleep-associated parameters were significantly higher in individuals with moderate and severe OSA compared to those with mild OSA. CRP levels did not differ between the two OSA severity groups. However, serum levels of HbA1c were significantly higher in the moderate/severe OSA group. Therefore, OSA severity may have a significant impact on glycemic control in obese individuals. Additionally, OSA severity did not appear to be further associated with systemic inflammation in obese individuals. Obese individuals may benefit not only from lifestyle modification, but also from OSA screening and treatment, particularly to prevent DM-associated disorders and conditions.

Background: Universities represent an important setting of everyday life for health promotion. The Healthy Campus Mainz project aims to develop an evidence-based and comprehensive student health management program covering physical, mental, and social health promotion. Hence, an initial health survey was performed in order to identify the students' health concerns and resources. Up until now, it remains unclear which topics to choose in a health survey among university students and which strategies can be recommended to receive an acceptable response rate or representative student sample within a university setting. The present paper contributes to the call for the present research topic “Public Health Promotion in University Students” by describing methods for health assessment. Therefore, the current paper aims to give an empirical example on how to perform a health survey among university students, focusing on (1) choosing topics for the survey and (2) methodological considerations of how to reach the target population.Methods: An online questionnaire including around 270 items was developed covering a comprehensive set of health topics. Participants were recruited via the university email. Mixed channels for survey promotion, such as lecture visits and social media, were used, accompanied by different monetary and non-monetary incentives. Descriptive analyses were performed to describe the sample.Results: A total of 5,006 participants (out of 31,213 registered students) viewed the first page of the questionnaire; of whom, 4,714 continued further. After a manual data cleaning according to the predefined criteria, the final sample was 4,351, demonstrating a response rate of 13.9%. Students from different study disciplines participated. However, some study disciplines showed a low participation rate, hence, making the results not free from some bias.Discussion: This survey is exceptional as it integrates a great variety of health aspects. The incentive strategy demonstrated promising results. Future research should try to improve target-group-specific recruitment strategies for the traditionally underrepresented groups, such as males and specific study disciplines. This would not only include advancing marketing strategies, but also refining the incentive strategy.

A poor preoperative functional capacity increases the perioperative risk. Therefore, a web-based exercise approach has been initiated for a careful supervision and individual support of patients during their perioperative cancer therapy. Here, we present the data of a 57-year-old patient, scheduled for esophagectomy. Beside a five-week neoadjuvant chemoradiotherapy (CRT), the patient performed 10 weeks of a web-based prehabilitation exercise training (preconditioning) and continued the exercise program for 14 weeks after surgery. The patient performed 42 of 44 recommended training sessions in the preconditioning period in his home environment. This corresponds to a mean of 131 (±38) min of total training per week. The patient performed 52 of 48 recommended training sessions in the postconditioning period. This corresponds to a mean of 165 (±87) min of total training per week. The patient could maintain his functional capacity during CRT and enhanced his submaximal performance level to the end of the intervention. The patient’s adherence to the program was noteworthy. The most important features of this approach are the personalized design and the flexible scheduling precisely in tune with the patient’s needs, concerns, and therapy related downtimes. Thus, the patient nearly fulfilled the exercise guidelines at a sufficient exercise intensity even during the neoadjuvant therapy. The preconditional exercise prevented a presumed CRT-induced and tumor-associated loss of functional capacity. The postoperative exercise led to a structured and adequate return into regular physical activities after surgery. Finally, this approach complements a comprehensive clinical care, in a health-promoting, cost-effective, and patient-safely manner.

Circulating, cell-free DNA (cfDNA) has been discussed as an upcoming blood-based biomarker in exercise physiology, reflecting important aspects of exercise load. cfDNA blood sampling has evolved from elaborate venous to efficient capillary sampling from the fingertips. In this study, we aimed to evaluate the principal feasibility of cfDNA blood sampling from the earlobe. Therefore, we obtained cfDNA concentrations from the fingertips, earlobe, and the antecubital vein during physiological exercise testing. Significantly higher concentrations were obtained from the earlobe compared to fingertip samples. All of the measurement methods showed good to excellent repeatability (ICCs of 0.85 to 0.93). In addition, the control experiments revealed that repeated sampling from the earlobe but not from the fingertips increased cfDNA at rest. In summary, cfDNA sampling is feasible for all sampling sources. However, at rest, cfDNA collected from the earlobe tend to increase over time in the absence of physical load, potentially limiting this sampling method.

[This corrects the article DOI: 10.1371/journal.pone.0197270.].

Physical exercise induces acute physiological changes leading to enhanced tissue cross-talk and a liberation of extracellular vesicles (EVs) into the circulation. EVs are cell-derived membranous entities which carry bioactive material, such as proteins and RNA species, and are important mediators of cell-cell-communication. Different types of physical exercise interventions trigger the release of diverse EV subpopulations, which are hypothesized to be involved in physiological adaptation processes leading to health benefits and longevity. Large EVs (“microvesicles” and “microparticles”) are studied frequently in the context of physical exercise using straight forward flow cytometry approaches. However, the analysis of small EVs (sEVs) including exosomes is hampered by the complex composition of blood, confounding the methodology of EV isolation and characterization. This mini review presents a concise overview of the current state of research on sEVs released upon physical exercise (ExerVs), highlighting the technical limits of ExerV analysis. The purity of EV preparations is highly influenced by the co-isolation of non-EV structures in the size range or density of EVs, such as lipoproteins and protein aggregates. Technical constraints associated with EV purification challenge the quantification of distinct ExerV populations, the identification of their cargo, and the investigation of their biological functions. Here, we offer recommendations for the isolation and characterization of ExerVs to minimize the effects of these drawbacks. Technological advances in the ExerV research field will improve understanding of the inter-cellular cross-talk induced by physical exercise leading to health benefits.

Introduction: The current literature provides no consensus that nutritional supplements (NS) may provide a gateway to doping. In particular, studies in recreational athletes are lacking. Within a previous cross-sectional empirical study, our group provided first evidence that the use of NS may provide a gateway for the use of doping substances in recreational triathletes. For the present paper, we refine the analysis of the triathletes’ survey in order to provide evidence for a NS gateway hypothesis in recreational athletes.Methods: A self-report, paper-and-pencil questionnaire was distributed to a sample of 2,997 competitive ironman and half-ironman (n = 1,076; 36.1%) triathletes. The randomized response technique (RRT) was used to assess the 12-month prevalence estimate for the use of doping substances. The prevalence for the use of NS was assessed by using direct questioning. Two-tailed (α = 0.05) large-sample z-tests were performed to assess whether the estimated prevalence for the use of doping substances differs significantly between users and nonusers of NS.Results: The 12-month prevalence estimate for the use of doping substances is significantly higher in athletes who report using NS (20.6%) compared to those who do not (11.4%; z = 2.595, p = 0.0097).Conclusion: The present results are consistent with the hypothesis that the use of NS provides a gateway to the use of doping substances. Therefore, doping prevention concepts should not primarily focus on preventing the use of doping substances per se, but should start one step earlier, namely by the use of NS.

Background: Universities represent an important setting for health promotion. The unique collective of university students is of particular relevance since they are the leaders, decision-makers, and parents of tomorrow. In this context, modifiable health influencing factors as well as interventions to prevent these, play a crucial role. Therefore, the present umbrella review aims to (i) provide an overview of review articles addressing epidemiological issues (prevalence and determinants) of modifiable health influencing factors in university students and (ii) to provide an overview of review articles addressing the evidence of interventions to promote/enhance modifiable health influencing factors in university students.Methods: A systematic literature search was performed in the databases PubMed, Cochrane Reviews Library und Web of Science according to the PRISMA guidelines. Only systematic reviews and meta-analyses were included. The AMSTAR-2-Tool was used for the quality assessment.Result: The initial search resulted in 10,726 records of which 81 fulfilled the inclusion criteria, with a further distinction in articles with an epidemiological focus (n = 39) and in articles with interventional approaches (n = 42). Topics of the different review articles ranged from physical activity over mental health, substance use, sleep, diet and nutrition, and media consumption. Many review articles had a specific focus on medical and nursing students and originated from the U.S.A., U.K., or China.Discussion: This umbrella review provides an overview of review articles on the epidemiology of modifiable health influencing factors and on the evidence of interventions targeting these factors among university students. Thereby, experts as well as stakeholders in the field could gain insights into crucial target points for health promotion. It identifies research gaps in terms of study region and groups of students.

Physical activity initiates a wide range of multi-systemic adaptations that promote mental and physical health. Recent work demonstrated that exercise triggers the release of extracellular vesicles (EVs) into the circulation, possibly contributing to exercise-associated adaptive systemic signalling. Circulating EVs comprise a heterogeneous collection of different EV-subclasses released from various cell types. So far, a comprehensive picture of the parental and target cell types, EV-subpopulation diversity and functional properties of EVs released during exercise (ExerVs) is lacking. Here, we performed a detailed EV-phenotyping analysis to explore the cellular origin and potential subtypes of ExerVs. Healthy male athletes were subjected to an incremental cycling test until exhaustion and blood was drawn before, during, and immediately after the test. Analysis of total blood plasma by EV Array suggested endothelial and leukocyte characteristics of ExerVs. We further purified ExerVs from plasma by size exclusion chromatography as well as CD9-, CD63- or CD81-immunobead isolation to examine ExerV-subclass dynamics. EV-marker analysis demonstrated increasing EV-levels during cycling exercise, with highest levels at peak exercise in all EV-subclasses analysed. Phenotyping of ExerVs using a multiplexed flow-cytometry platform revealed a pattern of cell surface markers associated with ExerVs and identified lymphocytes (CD4, CD8), monocytes (CD14), platelets (CD41, CD42, CD62P), endothelial cells (CD105, CD146) and antigen presenting cells (MHC-II) as ExerV-parental cells. We conclude that multiple cell types associated with the circulatory system contribute to a pool of heterogeneous ExerVs, which may be involved in exercise-related signalling mechanisms and tissue crosstalk.

Background: The aim of this observational cohort study was to explore the severity of liver disease in patients with suspected obstructive sleep apnea in Germany. Methods: Patients undergoing polysomnography or home sleep apnea testing (HSAT) as an evaluation for the presence of OSA were screened using vibration-controlled transient elastography (VCTE) and continuous attenuation parameter (CAP) with a Fibroscan ® Mini 430. Clinical and laboratory data were collected following the overnight exam. Results: In total, 78 patients (28 female (35.9%), mean age 54.2 years) with OSA defined by an apnea-hypopnea-index >5 events/hour were included between OCT 2020 and APR 2021. Patients exhibited a high metabolic risk profile with 17% known diabetes mellitus type 2 (T2D), 62% arterial hypertension, 14% hyperlipidemia and 36% BMI > 30 kg/m2. The prevalence of steatosis defined by a CAP > 280 dB/m was 54%. The prevalence of at least significant fibrosis was 16% (E > 9.0 kPa). Interestingly, patients with a snoring index above the median of 278/h showed significantly higher CAP-values (p = 0.0002). In addition, the proportion of oxygen saturations below 90% (t90) correlated with CAP-values (p = 0.02), as well as metabolic risk factors including increased waist circumference (p = 0.005) and body mass index (BMI) (p = 0.035). On the other hand, the apnea-hypopnea-index (AHI) as a marker of OSA severity did not correlate with VCTE, CAP or laboratory parameters. Conclusion: Patients with moderate to severe OSA have a high prevalence of hepatic steatosis. The snoring index is an easy-to-use clinical tool to identify patients at risk for relevant liver disease within the larger group of patients with OSA.

Abstract Background Patients undergoing surgery for esophageal cancer have a high risk for postoperative deterioration of lung function and pulmonary complications. This is partly due to one-lung ventilation during thoracotomy. This often accounts for prolonged stay on intensive care units, delayed postoperative reconvalescence and reduced quality of life. Socioeconomic disadvantages can result from these problems. Physical preconditioning has become a crucial leverage to optimize fitness and lung function in patients scheduled for esophagectomy, in particular during the time period of neoadjuvant therapy. Methods/Study design We designed a prospective multicenter randomized-controlled trial. The objective is to evaluate the impact of an internet-based exercise program on postoperative respiratory parameters and pneumonia rates in patients with Barrett’s carcinoma scheduled for esophagectomy. Patients are randomly assigned to either execute internet-based perioperative exercise program (iPEP), including daily endurance, resistance and ventilation training or treatment as usual (TAU). During neoadjuvant therapy and recovery, patients in the intervention group receive an individually designed intensive exercise program based on functional measurements at baseline. Personal feedback of the supervisor with customized training programs is provided in weekly intervals. Discussion This study will evaluate if an intensive individually adapted training program via online supervision during neoadjuvant therapy will improve cardiorespiratory fitness and reduce pulmonary complications following esophagectomy for Barrett’s cancer. Trial registration NCT02478996 , registered 26 May 2015.

The etiology of overweight and obesity is a mixture of genetic determinants, environmental factors, and health behaviors. Especially intra- and interpersonal inactive behaviors, here termed convenience, seems to play an important role. The objective was to develop and validate the Convenience Behavior Questionnaire (CBQ) to assess convenience-related items and their association with overweight and obesity in a large population. A sample of 1233 subjects aged 18–82 years from six population groups took part in a self-administered questionnaire. Test-retest reliability was estimated and the independent association between convenience-related items and overweight and obesity was investigated. Principal component analysis revealed three factors (avoidance behaviors, social interaction behaviors and domestic environmental factors) which explained 43.4% of the variance contributing to the CBQ. Cronbach's α ranged from 0.80–0.89. Test-retest reliability using intra-class correlation was acceptable ≥ 0.70. Forward stepwise logistic regression analysis, including gender, education level, age and TV viewing on weekends showed a positive relation of convenience behavior and overweight (OR: 1.40; 95% CI: 1.01–1.96; P = 0.048), while physical activity status was not significantly associated with overweight (OR: 1.09; 95% CI: 0.77–1.54; P = 0.629). The CBQ seems to be a reliable tool which considers non-traditional behaviors related to overweight development. Interestingly our findings revealed a better relationship between convenience-related behavior with overweight and obesity than the habitual physical activity score.

The worldwide prevalence of mental disorders in children and adolescents increased constantly. Additionally, the recommended amount of physical activity (PA) is not achieved by this age group. These circumstances are associated with negative impacts on their health status in later life and can lead to public health issues. The exposure to natural green environments (NGE) seems to be beneficial for human health. The compulsory school system offers great opportunities to reach every child with suitable health-related contents and interventions at an early stage. The concept of Education Outside the Classroom (EOtC) uses NGE and sets focus on PA. Therefore, EOtC might be a beneficial educational intervention to promote students health. The association between biological stress markers and sedentary behavior (SB) plus PA is insufficiently evaluated in school settings. This exploratory study aims to evaluate the association between students' cortisol, plus circulating cell-free deoxyribonucleic acid (cfDNA) levels, and their SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). We assessed data from an EOtC program (intervention group [IG], n = 37; control group [CG], n = 11) in three seasons (fall/spring/summer) in outdoor lessons (IG) in a NGE and normal indoor lessons (CG). SB and PA were evaluated by accelerometry, and cortisol and cfDNA levels by saliva samples. Fitted Bayesian hierarchical linear models evaluated the association between cortisol and cfDNA, and compositional SB/LPA/MVPA. A steady decline of cortisol in the IG is associated with relatively high levels of LPA (posterior mean = −0.728; credible interval [CRI 95%]: −1.268; −0.190). SB and MVPA tended to exhibit a similar effect in the CG. A high amount of cfDNA is positively associated with a relatively high amount of SB in the IG (posterior mean, 1.285; CRI: 0.390; 2.191), the same association is likely for LPA and MVPA in both groups. To conclude, LPA seems to support a healthy cortisol decrease in children during outdoor lessons in NGEs. Associations between cfDNA and SB/PA need to be evaluated in further research. This study facilitates the formulation of straightforward and directed hypotheses for further research with a focus on the potential health promotion of EOtC.

The rapidly increasing interest in fitness related sports over the past few years has been accompanied by a booming industry of nutritional supplements. Many of these substances have unproven benefits and are even potentially harmful to the user. The aim of this study was to determine the prevalence and reasons for nutritional supplement (NS) use among fitness studio visitors in Mainz (Germany), emphasizing new multi-ingredient based supplements such as pre workout boosters (PWBs). Some of the PWBs contain stimulants such as DMAA, N,α-DEPEA, DMAE and DMBA with so far unknown risks, harms and benefits. Four-Hundred and Ninety Two participants in 13 fitness studios completed a questionnaire on the use of nutritional supplements. Descriptive statistics and chi-square tests were used to examine differences in supplement use regarding training- and intake-reasons. About 57.0% of the participants reported the use of NS during the last 4 weeks. The all-time prevalence of creatine use was 28.7%, whereas 12.2% of the participants stated creatine use during the past 4 weeks. The all-time prevalence of PWB intake was 25.8%, whereas the last month prevalence was 11.8%. Among the group of PWB users, 20.5% stated to search specifically for substances such as DMAA, N,α-DEPEA, DMAE or DMBA. Logistic regression analysis showed positive relations between creatine use and the predictor variables gender, strength training and bodybuilding, as well as the stated exercisers' training reasons to increase physical- and sports-performance, and quality of life. PWB consumption was related to the variables gender, training frequency, and the reason for sports performance enhancement. Specific ingredient focus was related to the predictor variables competition participation and increase of mental performance. The results of the study show a high prevalence of PWB consumption among fitness studios visitors, which is comparable with creatine use. The predicting variables for consumption seem to be slightly different between the supplements, especially if the users are searching for stimulating agents. The current findings help to create preliminary consumption patterns and can help to identify potential endangered fitness studio visitors for prevention and risk communication, especially for PWBs.

STUDY OBJECTIVES:In order to increase the value of randomized response techniques (RRTs) as tools for studying sensitive issues, the present study investigated whether the prevalence estimate for a sensitive item [Formula: see text] assessed with the unrelated questionnaire method (UQM) is influenced by changing the probability of receiving the sensitive question p. MATERIAL AND METHODS:A short paper-and-pencil questionnaire was distributed to 1.243 university students assessing the 12-month prevalence of physical and cognitive doping using two versions of the UQM with different probabilities for receiving the sensitive question (p ≈ 1/3 and p ≈ 2/3). Likelihood ratio tests were used to assess whether the prevalence estimates for physical and cognitive doping differed significantly between p ≈ 1/3 and p ≈ 2/3. The order of questions (physical doping and cognitive doping) as well as the probability of receiving the sensitive question (p ≈ 1/3 or p ≈ 2/3) were counterbalanced across participants. Statistical power analyses were performed to determine sample size. RESULTS:The prevalence estimate for physical doping with p ≈ 1/3 was 22.5% (95% CI: 10.8-34.1), and 12.8% (95% CI: 7.6-18.0) with p ≈ 2/3. For cognitive doping with p ≈ 1/3, the estimated prevalence was 22.5% (95% CI: 11.0-34.1), whereas it was 18.0% (95% CI: 12.5-23.5) with p ≈ 2/3. Likelihood-ratio tests revealed that prevalence estimates for both physical and cognitive doping, respectively, did not differ significantly under p ≈ 1/3 and p ≈ 2/3 (physical doping: χ2 = 2.25, df = 1, p = 0.13; cognitive doping: χ2 = 0.49, df = 1, p = 0.48). Bayes factors computed with the Savage-Dickey method favored the null ("the prevalence estimates are identical under p ≈ 1/3 and p ≈ 2/3") over the alternative ("the prevalence estimates differ under p ≈ 1/3 and p ≈ 2/3") hypothesis for both physical doping (BF = 2.3) and cognitive doping (BF = 5.3). CONCLUSION:The present results suggest that prevalence estimates for physical and cognitive doping assessed by the UQM are largely unaffected by the probability for receiving the sensitive question p.

Attempts to establish a biomarker reflecting individual player load in intermittent sports such as football have failed so far. Increases in circulating DNA (cfDNA) have been demonstrated in various endurance sports settings. While it has been proposed that cfDNA could be a suitable marker for player load in intermittent sports, the effects on cfDNA of repeated sprinting as an essential feature in intermittent sports are unknown. For the first time, we assessed both alterations of cfDNA due to repeated maximal sprints and due to a professional football game.Nine participants were subjected to a standardised sprint training session with cross-over design of five maximal sprints of 40 meters with either "short" (1 minute) or "long" pauses (5 minutes). Capillary cfDNA and lactate were measured after every sprint and venous cfDNA before and after each series of sprints. Moreover, capillary cfDNA and lactate values were taken in 23 professional football players before and after incremental exercise testing, during the course of a training week at rest (baseline) and in all 17 enrolled players following a season game.Lactate and venous cfDNA increased more pronounced during "short" compared to "long" (1.4-fold, p = 0.032 and 1.7-fold, p = 0.016) and cfDNA correlated significantly with lactate (r = 0.69; p

Research has shown that outdoor educational interventions can lead to students' increased self-regulated motivational behavior. In this study, we searched into the satisfaction of basic psychological needs (BPN), i.e., autonomy support, the learners' experience of competence, and relatedness, both within the peer group and with their teachers, through outdoor learning. From 2014 to 2016, n = 281 students attended “research weeks” at a Student Science Lab in the Alpine National Park Berchtesgaden (Germany). The program is a curriculum-based one-week residential course, centered on a 2-day research expedition. Both before and after the course, students completed a composite questionnaire addressing BPN-satisfaction and overall motivational behavior in relation to the Self-Determination Index (SDI). At the latter time-point, students also reported on their experiences during the intervention. Questionnaire data was analyzed using a set of Bayesian General Linear Models with random effects. Those quantitative measures have been complemented by and contextualized with a set of qualitative survey methods. The results showed that the basic psychological needs influence the motivational behavior in both contexts equally, however on different scale levels. The basic needs satisfaction in the outdoor context is decisively higher than indoors. Moreover, the increment of competence-experience from the school context to the hands-on outdoor program appears to have the biggest impact to students' increased intrinsic motivation during the intervention. Increased autonomy support, student-teacher relations, and student-student relations have much less or no influence on the overall difference of motivational behavior. Gender does not influence the results. The contextualization partly supports those results and provide further explanation for the students' increased self-regulation in the outdoors. They add some explanatory thrust to the argument that outdoor teaching, be it during a residential week, or during occasional but regular sessions as integral part of the “normal” teaching, fosters intrinsic motivational behavior in science with lower secondary students.

Cells secrete extracellular vesicles (EVs) by default and in response to diverse stimuli for the purpose of cell communication and tissue homeostasis. EVs are present in all body fluids including peripheral blood, and their appearance correlates with specific physiological and pathological conditions. Here, we show that physical activity is associated with the release of nano-sized EVs into the circulation. Healthy individuals were subjected to an incremental exercise protocol of cycling or running until exhaustion, and EVs were isolated from blood plasma samples taken before, immediately after and 90 min after exercise. Small EVs with the size of 100–130 nm, that carried proteins characteristic of exosomes, were significantly increased immediately after cycling exercise and declined again within 90 min at rest. In response to treadmill running, elevation of small EVs was moderate but appeared more sustained. To delineate EV release kinetics, plasma samples were additionally taken at the end of each increment of the cycling exercise protocol. Release of small EVs into the circulation was initiated in an early phase of exercise, before the individual anaerobic threshold, which is marked by the rise of lactate. Taken together, our study revealed that exercise triggers a rapid release of EVs with the characteristic size of exosomes into the circulation, initiated in the aerobic phase of exercise. We hypothesize that EVs released during physical activity may participate in cell communication during exercise-mediated adaptation processes that involve signalling across tissues and organs.

Delayed-onset muscle soreness (DOMS) refers to dull pain and discomfort in people after participating in exercise, sport or recreational physical activities. The aim of this study was to detect underlying mechanical thresholds in an experimental model of DOMS.Randomised study to detect mechanical pain thresholds in a randomised order following experimentally induced DOMS of the non-dominant arm in healthy participants. Main outcome was the detection of the pressure pain threshold (PPT), secondary thresholds included mechanical detection (MDT) and pain thresholds (MPT), pain intensity, pain perceptions and the maximum isometric voluntary force (MIVF).Twenty volunteers (9 female and 11 male, age 25.2 ± 3.2 years, weight 70.5 ± 10.8 kg, height 177.4 ± 9.4 cm) participated in the study. DOMS reduced the PPT (at baseline 5.9 ± 0.4 kg/cm2) by a maximum of 1.5 ± 1.4 kg/cm2 (-24%) at 48 hours (p < 0.001). This correlated with the decrease in MIVF (r = -0.48, p = 0.033). Whereas subjective pain was an indicator of the early 48 hours, the PPT was still present after 72 hours (r = 0.48, p = 0.036). Other mechanical thresholds altered significantly due to DOMS, but did show no clinically or physiologically remarkable changes.Functional impairment following DOMS seems related to the increased excitability of high-threshold mechanosensitive nociceptors. The PPT was the most valid mechanical threshold to quantify the extent of dysfunction. Thus PPT rather than pain intensity should be considered a possible marker indicating the athletes' potential risk of injury.

Creatine kinase (CK) is a marker for muscle cell damage with limited potential as marker for training load in strength training. Recent exercise studies identified cell free DNA (cfDNA) as a marker for aseptic inflammation and cell damage. Here we overserved in a pilot study the acute effects during strength exercise and chronic effects of regular strength training on cfDNA concentrations over a period of four weeks in three training groups applying conservation training (CT) at 60% of the 1 repetition maximum, high intensity-low repetition training (HT) at 90% of the 1 repetition maximum and differential training (DT) at 60% of the 1 repetition maximum. EDTA-plasma samples were collected before every training session, and on the first and last training day repeatedly after every set of exercises. CfDNA increased significantly by 1.62-fold (mean (±SD) before first exercise: 8.31 (2.84) ng/ml, after last exercise 13.48 (4.12) ng/ml) across all groups within a single training session (p