Three-week sprint interval training (SIT) reduces cell-free DNA and low-frequency fatigue but does not induce VO2max improvement in older men.

PURPOSE: This study aimed to investigate the impact of sprint interval training (SIT) on both the acute and 3-week modulations of cell-free DNA (cfDNA), as well as its association with neuromuscular fatigue and physical performance in healthy young and old men. METHODS: Ten young (20-25 year old) and nine elderly (63-72 year old) healthy men performed nine SIT sessions consisting of 4-to-6-all-out cycling repetitions of 30 s interspaced with 4-min rest intervals. We compared the maximal voluntary contractions torque, central activation ratio, low-frequency fatigue (LFF), and cfDNA concentrations between the groups before, immediately after, 1 h after, and 24 h after the first and ninth SIT sessions. RESULTS: The plasma cfDNA levels were increased post-exercise (from 1.4 ± 0.258 to 1.91 ± 0.278 ng/ml (P < 0.01) on a log10 scale), without significant differences between the groups. However, older individuals showed a slight decrease in the baseline cfDNA values, from 1.39 ± 0.176 to 1.29 ± 0.085 ng/ml on a log10 scale, after 3 weeks (P = 0.043). Importantly, the elevation of the post-exercise cfDNA values was correlated with an increase in LFF in both groups. Three weeks of SIT induced an improvement in the recovery of LFF (main session effect, P = 0.0029); however, only the young group showed an increase in aerobic capacity (VO2max) (from 40.8 ± 6.74 to 43.0 ± 5.80 ml/kg/min, P = 0.0039). CONCLUSION: Three weeks of SIT diminished the baseline cfDNA values in the old group, together with an improvement in the recovery of LFF. However, VO2max was increased only in the young group.

Cigarette Smoking, Risky Alcohol Consumption, and Marijuana Smoking among University Students in Germany: Identification of Potential Sociodemographic and Study-Related Risk Groups and Predictors of Consumption.

(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.

Assessing the Prevalence of Doping Among Elite Athletes: An Analysis of Results Generated by the Single Sample Count Method Versus the Unrelated Question Method.

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.

Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles.

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.

Extracellular vesicles (EVs) are tiny particles released by cells, carrying unique biomolecules specific to their cell of origin. EVs from the central nervous system (CNS) can reach the blood, where they could serve as liquid-biopsy markers for diagnosing brain diseases like neurodegenerative disorders and tumors. This study evaluated a flow cytometry platform (here termed EV Neuro assay), which can detect multiple EV-associated markers simultaneously, to assess its potential for identifying CNS-derived EVs and disease-specific markers in complex samples including the blood. The study compared different sample materials and methods for isolating EVs. We found distinct EV profiles in EVs derived from glioblastoma and human astrocytes, with signal intensities increasing as more EVs were present. Analyzing serum or plasma from patients with brain diseases and healthy individuals, we observed that EV marker intensities were varying between individuals. Importantly, data normalization improved the identification of disease-specific markers, such as CD36⁺EVs in glioblastoma and GALC⁺EVs in multiple sclerosis, which were significantly higher in disease compared to healthy controls. Advanced clustering analysis techniques effectively distinguished glioblastoma patients from controls. Furthermore, a potential correlation between CD107a⁺EVs and neurofilament levels in multiple sclerosis patients was discovered. Overall, the semi-quantitative EV Neuro assay proved useful for profiling EVs in complex samples. However, for more reliable results in biomarker studies, larger sample cohorts and higher effect sizes are necessary. Nonetheless, this initial trial confirmed the potential of the EV Neuro assay for discovering disease-associated EV markers and monitoring circulating EV profiles in CNS diseases.

Evidence for the utility of cfDNA plasma concentrations to predict disease severity in COVID-19: a retrospective pilot study.

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.

Predicting Injury and Illness with Machine Learning in Elite Youth Soccer: A Comprehensive Monitoring Approach over 3 Months.

The search for monitoring tools that provide early indication of injury and illness could contribute to better player protection. The aim of the present study was to i) determine the feasibility of and adherence to our monitoring approach, and ii) identify variables associated with up-coming illness and injury. We incorporated a comprehensive set of monitoring tools consisting of external load and physical fitness data, questionnaires, blood, neuromuscular-, hamstring, hip abductor and hip adductor performance tests performed over a three-month period in elite under-18 academy soccer players. Twenty-five players (age: 16.6 ± 0.9 years, height: 178 ± 7 cm, weight: 74 ± 7 kg, VO2max: 59 ± 4 ml/min/kg) took part in the study. In addition to evaluating adherence to the monitoring approach, data were analyzed using a linear support vector machine (SVM) to predict illness and injuries. The approach was feasible, with no injuries or dropouts due to the monitoring process. Questionnaire adherence was high at the beginning and decreased steadily towards the end of the study. An SVM resulted in the best classification results for three classification tasks, i.e., illness prediction, illness determination and injury prediction. For injury prediction, one of four injuries present in the test data set was detected, with 96.3% of all data points (i.e., injuries and non-injuries) correctly detected. For both illness prediction and determination, there was only one illness in the test data set that was detected by the linear SVM. However, the model showed low precision for injury and illness prediction with a considerable number of false-positives. The results demonstrate the feasibility of a holistic monitoring approach with the possibility of predicting illness and injury. Additional data points are needed to improve the prediction models. In practical application, this may lead to overcautious recommendations on when players should be protected from injury and illness.

Videos using different message strategies to promote the interruption of sedentary behavior in university students during online lectures - A pilot study.

Background: Sedentary 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. Objective: This 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. Methods: During 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. Results: Approximately 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 < 0.05). Identification with characters significantly predicted the intentions to reduce SB (p < 0.001), with a large effect of the overall regression model (R2corr = 0.47). Conclusion: Considering the increased digitalization in general and restrictions due to COVID-19 pandemic, videos seem to be a useful tool to interrupt SB among university students during online lectures. Narrative formats could facilitate the intention to reduce SB, which in turn could have a positive impact on the interruption of SB. However, further research on effective communication and message strategies is needed.

Acute physiological responses to a pyramidal exercise protocol and the associations with skin temperature variation in different body areas.

This study aimed to examine the skin temperature (Tsk) variations in five regions of interest (ROI) to assess whether possible disparities between the ROI's Tsk could be associated with specific acute physiological responses during cycling. Seventeen participants performed a pyramidal load protocol on a cycling ergometer. We synchronously measured Tsk in five ROI with three infrared cameras. We assessed internal load, sweat rate, and core temperature. Reported perceived exertion and calves' Tsk showed the highest correlation (r = -0.588; p < 0.01). Mixed regression models revealed that the heart rate and reported perceived exertion were inversely related to calves' Tsk. The exercise duration was directly associated with the nose tip and calf Tsk but inversely related to the forehead and forearm Tsk. The sweat rate was directly related to forehead and forearm Tsk. The association of Tsk with thermoregulatory or exercise load parameters depends on the ROI. The parallel observation of the face and calf Tsk could indicate simultaneously the observation of acute thermoregulatory needs and individual internal load. The separate Tsk analyses of individual ROI appear more suitable to examine specific physiological response than a mean Tsk of several ROI during cycling.

Blood-Based Biomarkers for Managing Workload in Athletes: Perspectives for Research on Emerging Biomarkers.

At present, various blood-based biomarkers have found their applications in the field of sports medicine. This current opinion addresses biomarkers that warrant consideration in future research for monitoring the athlete training load. In this regard, we identified a variety of emerging load-sensitive biomarkers, e.g., cytokines (such as IL-6), chaperones (such as heat shock proteins) or enzymes (such as myeloperoxidase) that could improve future athlete load monitoring as they have shown meaningful increases in acute and chronic exercise settings. In some cases, they have even been linked to training status or performance characteristics. However, many of these markers have not been extensively studied and the cost and effort of measuring these parameters are still high, making them inconvenient for practitioners so far. We therefore outline strategies to improve knowledge of acute and chronic biomarker responses, including ideas for standardized study settings. In addition, we emphasize the need for methodological advances such as the development of minimally invasive point-of-care devices as well as statistical aspects related to the evaluation of these monitoring tools to make biomarkers suitable for regular load monitoring.

Blood-Based Biomarkers for Managing Workload in Athletes: Considerations and Recommendations for Evidence-Based Use of Established Biomarkers.

Blood-based biomarkers can provide an objective individualized measure of training load, recovery, and health status in order to reduce injury risk and maximize performance. Despite enormous potentials, especially owing to currently evolving technology, such as point-of-care testing, and advantages, in terms of objectivity and non-interference with the training process, there are several pitfalls in the use and interpretation of biomarkers. Confounding variables such as preanalytical conditions, inter-individual differences, or an individual chronic workload can lead to variance in resting levels. In addition, statistical considerations such as the detection of meaningful minimal changes are often neglected. The lack of generally applicable and individual reference levels further complicates the interpretation of level changes and thus load management via biomarkers. Here, the potentials and pitfalls of blood-based biomarkers are described, followed by an overview of established biomarkers currently used to support workload management. Creatine kinase is discussed in terms of its evidence for workload management to illustrate the limited applicability of established markers for workload management to date. We conclude with recommendations for best practices in the use and interpretation of biomarkers in a sport-specific context.

Sedentary time of university students before and during the COVID-19 pandemic: Risk groups and pre-pandemic predictors using cross-sectional and longitudinal data.

Background: The 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. Methods: Two 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. Results: Of 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. Conclusion: Even 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.

An exploratory, intra- and interindividual comparison of the deep neural network automatically measured calf surface radiation temperature during cardiopulmonary running and cycling exercise testing: A preliminary study.

Non-invasive and contactless infrared thermography (IRT) measurements have been claimed to indicate acute neural, cardiovascular, and thermoregulatory adaptations during exercise. Due to challenging comparability, reproducibility, and objectivity, investigations considering different exercise types and intensities, and automatic ROI analysis are currently needed. Thus, we aimed to examine surface radiation temperature (Tsr) variations during different exercise types and intensities in the same individuals, ROI, and environmental conditions. Ten healthy, active males performed a cardiopulmonary exercise test on a treadmill in the first week and on a cycling ergometer the following week. Respiration, heart rate, lactate, rated perceived exertion, the mean, minimum, and maximum Tsr of the right calf (CTsr (°C)), and the surface radiation temperature pattern (CPsr) were explored. We executed two-way rmANOVA and Spearman's rho correlation analyses. Across all IRT parameters, mean CTsr showed the highest association to cardiopulmonary parameters (E.g., oxygen consumption: rs = -0.612 (running); -0.663 (cycling); p < .001). A global significant difference of CTsr was identified between all relevant exercise test increments for both exercise-types (p < .001; η2p = .842) and between both exercise-types (p = .045; η2p = .205). Differences in CTsr between running and cycling significantly appeared after a 3-min recovery period, whereas lactate, heart rate, and oxygen consumption were not different. High correlations between the CTsr values extracted manually and the CTsr values processed automatically by a deep neural network were identified. The applied objective time series analysis enables crucial insights into intra- and interindividual differences between both tests. CTsr variations indicate different physiological demands between incremental running and cycling exercise testing. Further studies applying automatic ROI analyses are needed to enable the extensive analysis of inter- and intraindividual factors influencing the CTsr variation during exercise to allow determine the criterion and predictive validity of IRT parameters in exercise physiology.

Physical Activity as a Treatment for Cancer-Related Fatigue in Children, Adolescents and Young Adults: A Systematic Review.

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.

Serum Ferritin Levels in Severe Obstructive Sleep Apnea.

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: <15/h vs. moderate OSA: 15-30/h vs. severe 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.

Kinetics of Plasma Cell-Free DNA under a Highly Standardized and Controlled Stress Induction.

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.

Resilience and stability of the CF- intestinal and respiratory microbiome during nutritional and exercise intervention.

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.

Central Apneic Event Prevalence in REM and NREM Sleep in OSA Patients: A Retrospective, Exploratory Study.

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.

Choice matters: Pupils' stress regulation, brain development and brain function in an outdoor education project.

BACKGROUND: Education outside the classroom (EOtC) is considered beneficial to children's physical and mental health. Especially, stress resilience has been linked to nature experience. AIMS: This study experimentally explored the effects of pupils' autonomy support (AUT) and physical activity (PA) on their biological stress responses and brain development in EOtC. SAMPLE: The study comprised 48 fifth and sixth graders. METHODS: The intervention consisted of one day/week taught in a forest over one school year. Structural magnetic resonance imaging (MRI) was conducted at the beginning and the end of the school year, functional MRI under a stress condition at the end. Regions of interest were amygdala, hippocampus and the anterior cingulate cortex (ACC). All other measures were obtained at the beginning, at mid-term and at the end of the school year. PA was measured using accelerometry. Cortisol levels were obtained three times during the examined school days. AUT was measured with a paper-based survey. Data were analysed using Bayesian multivariate models. RESULTS: EOtC students exhibit more efficient regulation of biological stress-reactivity and show a reduction of cortisol over the day associated with light PA in the forest. Cortisol is further associated with amygdala activation in the stress condition. Cerebral structural change is best explained by age; however, AUT has a positive direct effect on the maturation of the ACC, which is stronger in EOtC. CONCLUSIONS: Our results support the idea that autonomy supportive teaching fosters cerebral maturation and that EOtC can have a positive effect on biological stress regulation.

Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA.

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.

Obstructive Sleep Apnea Disrupts Glycemic Control in Obese Individuals.

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.