Exploring sex differences in blood-based biomarkers following exhaustive exercise using bioinformatics analysis.

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 ( V ˙ O 2 max ): 59.4 ± 7.5 ml · min-1 · kg-1; 8 women, age: 26.8 ± 6.1 years, V ˙ O 2 max : 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.

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.

A training goal-oriented categorization model of high-intensity interval training.

There are various categorization models of high-intensity interval training (HIIT) in the literature that need to be more consistent in definition, terminology, and concept completeness. In this review, we present a training goal-oriented categorization model of HIIT, aiming to find the best possible consensus among the various defined types of HIIT. This categorization concludes with six different types of HIIT derived from the literature, based on the interaction of interval duration, interval intensity and interval:recovery ratio. We discuss the science behind the defined types of HIIT and shed light on the possible effects of the various types of HIIT on aerobic, anaerobic, and neuromuscular systems and possible transfer effects into competition performance. We highlight various research gaps, discrepancies in findings and not yet proved know-how based on a lack of randomized controlled training studies, especially in well-trained to elite athlete cohorts. Our HIIT "toolbox" approach is designed to guide goal-oriented training. It is intended to lay the groundwork for future systematic reviews and serves as foundation for meta-analyses.

Adding LIT to HIIT - Is Low-Intensity Training Vital for Endurance-Trained Athletes during a 7-day HIIT Shock Microcycle?

PURPOSE: To investigate the effects of a 7-day high-intensity interval training shock microcycle (HIIT-SM) with or without additional low-intensity training (LIT) on aerobic fitness and endurance performance compared to a control group. METHODS: Thirty-three endurance-trained athletes (7 women, 26 men, mean ± SD: age, 30.2 ± 6.9 yr; maximal oxygen uptake (V̇O 2max ), 59.8 ± 4.9 mL·min -1 ·kg -1 ) performed exercise testing at T1 and were randomly assigned to one of three groups: i) HSM: 10 running-based HIIT sessions (5 x 4 min at 90-95% maximal heart rate) over 7 days ii) HSM + LIT: equal to HSM with additional 30-min of LIT after each HIIT iii) CG: regular training. Exercise testing was repeated 3 days (T2), 7 days (T3), and 14 days (T4) after the intervention. A 5-km time trial (TT 5km ) was performed 3-4 days before T1 and 10-11 days after the intervention. Data was analyzed by two-way repeated-measures ANOVA. RESULTS: No interaction effect was found for V̇O 2max (P = 0.170, p η 2 = 0.09), peak power output (P = 0.734, p η 2 = 0.04), and work economy (P = 0.804, p η 2 = 0.03). There was an interaction for velocity at lactate threshold (P = 0.006, p η 2 = 0.18) with increased velocity in HSM at T2 (3.2%, P = 0.030), T3 (4%, P = 0.006), T4 (4%, P = 0.003), as well as in HSM + LIT for T2 (3.2%, P = 0.011), while CG showed no change. There was an interaction for TT 5km (P = 0.044, p η 2 = 0.19) with HSM improving 2.7% (P = 0.003), HSM + LIT 2.3% (P = 0.010), while CG was on average - 0.3% (P = 0.821) slower. CONCLUSIONS: HIIT-SM with or without additional LIT has negligible effects on V̇O 2max but improves other key endurance variables in endurance-trained athletes. No superiority of either intervention group was demonstrated. Therefore, additional LIT during HIIT-SM is not beneficial.

Unraveling the mystery of isocaloric endurance training - Influence of exercise modality, biological sex, and physical fitness.

BACKGROUND: A sedentary lifestyle with low energy expenditure (EE) is associated with chronic diseases and mortality. Barriers such as "lack of time" or "lack of motivation" are common reasons why physical exercise is neglected in the general population. To optimize EE in the time available, time-efficient but also enjoyable types of exercise are required. We therefore used an isocaloric approach to systematically investigate the effects of six different endurance exercise modalities on metabolic, mechanical, cardiorespiratory, and subjective variables in relation to biological sex and physical fitness. METHODS: Out of 104, 92 healthy participants (21 recreationally trained and 18 trained females, 25 recreationally trained and 28 trained males) were subjected to physiological exercise testing to determine the exercise intensities for six exercise modalities, i.e., three different high-intensity interval training (HIIT) protocols (5 × 4 min, 15 × 1 min, 30 × 30 sec intervals), threshold (THR), speed endurance production (SEP), and low-intensity continuous endurance training (LIT). One of three HIIT sessions served as the reference for the subsequent isocaloric exercise modalities which were completed in randomized order. Metabolic and mechanical variables, i.e., EE during exercise, time to isocaloric EE (Tiso), relative and absolute fat contribution, post-exercise oxygen consumption (EPOC), mechanical energy, as well as cardiorespiratory and subjective variables, i.e., heart rate, oxygen uptake response, rating of perceived exertion, and enjoyment were assessed. Data were analyzed using a 6 × 2 × 2 repeated-measures ANOVA. RESULTS: All three versions of HIIT and THR achieved the same EE during exercise for the same training duration. We found that LIT had a 1.6-fold (p < 0.001) and SEP a 1.3-fold (p < 0.001) longer Tiso compared to HIIT with no effects of biological sex (p = 0.42, pη2 = 0.01) or physical fitness (p = 0.09, pη2 = 0.04). There was a main effect of exercise modality on EPOC (p < 0.001, pη2 = 0.76) with highest values for HIIT 30 × 30 (p = 0.032) and lowest for LIT (p < 0.001). The highest relative and absolute amounts of fatty acids were measured during LIT (p < 0.001), and the lowest values were obtained during HIIT modalities. HIIT 30 × 30 was the most enjoyable version of HIIT (p = 0.007), while THR was the least enjoyable exercise modality (p = 0.008). CONCLUSION: HIIT modalities are time-saving and enjoyable, regardless of sex and physical fitness. The results illustrate the relationship between exercise modality and metabolic, physiological, and subjective responses, and are thus of great interest to healthy individuals seeking time-saving and enjoyable exercise options.

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.

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.

Evidence-Based Recovery in Soccer - Low-Effort Approaches for Practitioners.

Strategies to improve recovery are widely used among soccer players at both amateur and professional levels. Sometimes, however, recovery strategies are ineffective, improperly timed or even harmful to players. This highlights the need to educate practitioners and athletes about the scientific evidence of recovery strategies as well as to provide practical approaches to address this issue. Therefore, recent surveys among soccer athletes and practitioners were reviewed to identify the recovery modalities currently in use. Each strategy was then outlined with its rationale, its physiological mechanisms and the scientific evidence followed by practical approaches to implement the modality. For each intervention, practical and particularly low-effort strategies are provided to ensure that practitioners at all levels are able to implement them. We identified numerous interventions regularly used in soccer, i.e., sleep, rehydration, nutrition, psychological recovery, active recovery, foam-rolling/massage, stretching, cold-water immersion, and compression garments. Nutrition and rehydration were classified with the best evidence, while cold-water immersion, compression garments, foam-rolling/massage and sleep were rated with moderate evidence to enhance recovery. The remaining strategies (active recovery, psychological recovery, stretching) should be applied on an individual basis due to weak evidence observed. Finally, a guide is provided, helping practitioners to decide which intervention to implement. Here, practitioners should rely on the evidence, but also on their own experience and preference of the players.

Feasibility of Cell-Free DNA Measurement from the Earlobe during Physiological Exercise Testing.

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.

The Salzburg 10/7 HIIT shock cycle study: the effects of a 7-day high-intensity interval training shock microcycle with or without additional low-intensity training on endurance performance, well-being, stress and recovery in endurance trained athletes-study protocol of a randomized controlled trial.

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.

Comprehensive training load monitoring with biomarkers, performance testing, local positioning data, and questionnaires - first results from elite youth soccer.

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.

Twelve-Week Internet-Based Individualized Exercise Program in Adults With Systemic Lupus Erythematosus: Protocol for a Randomized Controlled Trial.

BACKGROUND: Systemic lupus erythematosus is a systemic autoimmune disease, which is associated with high cardiovascular risk, a predisposition to metabolic disorders, muscle wasting, and fatigue. Exercise therapy has become an important part of the long-term treatment of comorbidities in systemic lupus erythematosus. Exercise can lead to various benefits in patients with systemic lupus erythematosus such as increased aerobic capacity and exercise tolerance, resulting in an increased quality of life, decreased depression, and decreased fatigue. At the moment, no evidence-based treatment guidelines that recommend exercise for patients with systemic lupus erythematosus exist. Also, the efficacy of different training programs requires further investigation. OBJECTIVE: This study focuses on the feasibility, efficacy, and safety of an internet-based exercise program in patients with systemic lupus erythematosus. Furthermore, we investigate the feasibility and efficiency of anaerobic training compared to aerobic training. METHODS: Overall, patients with systemic lupus erythematosus from the Division of Nephrology, Rheumatology, and Immunology outpatient clinic of the University Medical Center Mainz who are clinically stable status are included and randomized in an aerobic exercise group (n=10), anaerobic exercise group (n=10), or treatment as usual group (n=10). After completing initial clinical testing and physical fitness tests, patients undergo supervised 12-week online exercise programs, receiving weekly individualized training plans adapted to their physical performance. The primary outcome is change in physical fitness (VO2 peak) after 12 weeks compared to baseline. Secondary outcomes are disease activity measured via laboratory results (complement, autoantibodies) and questionnaires, as well as changes in muscle mass (anaerobic exercise group), results of the Chair-Stand test, and measurements of circulating cell-free DNA and extracellular vesicles. RESULTS: The study was registered in May 2019. Enrollment began in May 2019. Of 40 patients who were initially screened, 30 patients fulfilled the inclusion criteria and were included in the study; 1 participant withdrew prior to the start of the exercise program. Among the 25 patients who completed the study, no serious adverse events have been reported; 3 participants withdrew during the program (due to frequent colds, n=1; Crohn relapse, n=1; physical strain, n=1), and 1 participant has not yet completed the program. Data analysis is ongoing, and results are expected to be submitted for publication in January 2021. CONCLUSIONS: We expect the online exercise intervention to be a feasible and efficient tool to provide regular individualized exercise for patients with systemic lupus erythematosus. TRIAL REGISTRATION: ClinicalTrials.gov NCT03942718; http://clinicaltrials.gov/ct2/show/NCT03942718. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18291.

Physical determinants of vault performance and their age-related differences across male junior and elite top-level gymnasts.

In order to perform difficult vaults in artistic gymnastics, athletes have to achieve high run-up speeds within the limited run-up distance (25m). However, the physical parameters that contribute to a high run-up speed and their age-related differences remain elusive. Hence, the aim of this study was 1) to investigate interrelations between difficulty value (D-score) and run-up kinematics of Handspring/Tsukahara and Yurchenko vaults as well as lower body power (25m-sprint, explosive and reactive strength) and 2) to explore age-related differences of these parameters across junior and elite gymnasts performing Handspring/Tsukahara vaults. For this purpose, the data (of the above mentioned parameters) of 47 top-level male elite and junior gymnasts aged 14.3 to 28.3 of performance testing, gathered over three years, were analysed. We found that D-score of Handspring/Tsukahara (n = 33) was strongly correlated with run-up speed (r = 0.79; p < 0.01). Further, 25m sprint speed (r = 0.85; p < 0.01) was significantly associated with run-up speed of Handspring/Tsukahara-vaults. There were no significant relationships with the D-score of Yurchenko (n = 14). Looking at the age-related differences of Handspring/Tsukahara, D-score increased significantly from junior to elite level (+11.6%; p < 0.01). The comparison between consecutive age-groups revealed that the U19 group had higher run-up speeds, step lengths, body weights and heights than the U17 group, while the U21 group achieved significantly higher speeds (run-up, 25m-sprint) and explosive strength than the U19 group. We concluded 1) that the optimization of important physical determinants may increase the potential to perform more difficult Handspring/Tsukahara vaults and 2) that first growth and maturation and later improvements of lower body power led to higher run-up speeds of Handspring/Tsukahara in the subsequent age-group. Therefore, based on performance testing of the lower limbs, training recommendations should be given specifically to the requirements of the competition vault.

Circulating, Cell-Free DNA for Monitoring Player Load in Professional Football.

Purpose: Player monitoring in elite sport settings is becoming increasingly important. Questionnaire-based methods and biomarkers such as circulating, cell-free DNA (cfDNA) are suggested for load monitoring. cfDNA concentrations were shown to increase depending on total distance covered in football and were associated with overtraining in weight lifters. Thus, the objective of this study was to examine whether cfDNA is feasible as a monitoring tool in elite football players. Methods: Capillary blood samples from 22 male elite football players were collected over 4 mo of a regular season. Sampling was conducted the day before, 1 day after, or several days after regular-season games and/or training. In addition, each player filled in a visual analogue scale (VAS) questionnaire including the items "general perceived exertion," "muscular fatigue," and "mental fatigue." Performance during training and games was tracked by the Catapult system and with the OPTA system, respectively. Results: cfDNA values were significantly elevated in players the day after regular-season games (1.4-fold; P = .0004) in line with the scores of the VAS. Both parameters showed significantly higher values during midweek-game weeks. cfDNA concentrations correlated with training data, and VAS was correlated with the tracking of the season games. However, cfDNA and VAS did not correlate with each other. Conclusions: cfDNA concentrations at rest and VAS scores are influenced by previous load in professional football players. Future studies will reveal whether cfDNA might serve as a practically applicable marker for player load in football players.

Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation.

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.

Circulating, cell-free DNA as a marker for exercise load in intermittent sports.

BACKGROUND: 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. METHODS: 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. RESULTS: 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<0.001). Incremental exercise testing increased cfDNA 7.0-fold (p<0.001). The season game increased cfDNA 22.7-fold (p<0.0001), while lactate showed a 2.0-fold (p = 0.09) increase compared to baseline. Fold-changes in cfDNA correlated with distance covered during game (spearman's r = 0.87, p = 0.0012), while no correlation between lactate and the tracking data could be found. DISCUSSION: We show for the first time that cfDNA could be an objective marker for distance covered in elite intermittent sports. In contrast to the potential of more established blood-based markers like IL-6, CK, or CRP, cfDNA shows by far the strongest fold-change and a high correlation with a particular load related aspect in professional football.

Individualized Web-Based Exercise for the Treatment of Depression: Randomized Controlled Trial.

BACKGROUND: Due to the high prevalence of depressive disorders, it is mandatory to develop therapeutic strategies that provide universal access and require limited financial and human resources. Web-based therapeutic approaches fulfill these conditions. OBJECTIVE: The objective of our study was to assess the feasibility, acceptability, and efficacy of a supervised, individualized 8-week Web-based exercise intervention conducted for patients with moderate to severe depression. METHODS: We recruited 20 patients with unipolar depression and randomly assigned them into 2 groups (intervention, exercise program group, n=14, and control, treatment-as-usual group, n=6). At baseline, depressive symptoms were rated via the Quick Inventory of Depressive Symptomatology (QIDS) by patients themselves (QIDS-self-report, QIDS-SR) and by a blinded psychiatrist (QIDS-clinician rating, QIDS-C). In addition, performance diagnostics (lactate analysis, spiroergometry during a treadmill walking test) were conducted. Quality of life was assessed via the Short Form-36 questionnaire (SF-36) and self-efficacy via the General Self-Efficacy scale (GSE). In addition, habitual physical activity (HPA) was determined via the Baecke questionnaire. Participants of the intervention group received exercise schedules once weekly with endurance and strength training instructions. Rating of depressive symptoms was repeated after 6-12 days and 8 weeks; performance diagnostics and the completion of all the questionnaires were repeated after 8 weeks only. RESULTS: The severity of depression subsided significantly in the intervention group after 8 weeks (median change in QIDS-SR: -5; interquartile range, IQR: -2 to -10), although it was already evident within the first 6-12 days (median change in QIDS-SR: -6; IQR: -2 to -8). During the intervention, participants undertook a median of 75 (IQR: 63 to 98) minutes of endurance training per week or 84% (16 [IQR: 9 to 19] of 19 [IQR: 15 to 21]) recommended endurance units in total. In addition, 9 (IQR: 4 to 12) of 10 (IQR: 8 to 13) recommended strength training exercise units were conducted during the 8 weeks. Performance diagnostics revealed a substantial increase in the maximum output in Watt for the intervention group after 8 weeks. Moreover, the intervention showed a favorable effect on SF-36 items "emotional well-being" and "social functioning" as well as on GSE and HPA scores. CONCLUSIONS: Our individualized Web-based exercise intervention for moderate to severe depression was highly accepted by the patients and led to a significant and clinically relevant improvement of depressive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT02874833; https://clinicaltrials.gov/ct2/show/NCT02874833 (Archived by WebCite at http://www.webcitation.org/72ZUUR4tE).

Applicability of a Web-Based, Individualized Exercise Intervention in Patients With Liver Disease, Cystic Fibrosis, Esophageal Cancer, and Psychiatric Disorders: Process Evaluation of 4 Ongoing Clinical Trials.

BACKGROUND: In the primary and secondary prevention of civilization diseases, regular physical activity is recommended in international guidelines to improve disease-related symptoms, delay the progression of the disease, or to enhance postoperative outcomes. In the preoperative context, there has been a paradigm shift in favor of using preconditioning concepts before surgery. Web-based interventions seem an innovative and effective tool for delivering general information, individualized exercise recommendations, and peer support. OBJECTIVE: Our first objective was to assess feasibility of our Web-based interventional concept and analyze similarities and differences in a sustained exercise implementation in different diseases. The second objective was to investigate the overall participants' satisfaction with our Web-based concept. METHODS: A total of 4 clinical trials are still being carried out, including patients with esophageal carcinoma scheduled for oncologic esophagectomy (internet-based perioperative exercise program, iPEP, study), nonalcoholic fatty liver disease (hepatic inflammation and physical performance in patients with nonalcoholic steatohepatitis, HELP, study), depression (exercise for depression, EXDEP, study), and cystic fibrosis (cystic fibrosis online mentoring for microbiome, exercise, and diet, COMMED, study). During the intervention period, the study population had access to the website with disease-specific content and a disease-specific discussion forum. All participants received weekly, individual tailored exercise recommendations from the sports therapist. The main outcome was the using behavior, which was obtained by investigating the log-in rate and duration. RESULTS: A total of 20 participants (5 from each trial) were analyzed. During the intervention period, a regular contact and a consequent implementation of exercise prescription were easily achieved in all substudies. Across the 4 substudies, there was a significant decrease in log-in rates (P<.001) and log-in durations (P<.001) over time. A detailed view of the different studies shows a significant decrease in log-in rates and log-in durations in the HELP study (P=.004; P=.002) and iPEP study (P=.02; P=.001), whereas the EXDEP study (P=.58; P=.38) and COMMED study (P=.87; P=.56) showed no significant change over the 8-week intervention period. There was no significant change in physical activity within all studies (P=.31). Only in the HELP study, the physical activity level increased steadily over the period analyzed (P=.045). Overall, 17 participants (85%, 17/20) felt secure and were not scared of injury, with no major differences in the subtrials. CONCLUSIONS: The universal use of the Web-based intervention appears to be applicable across the heterogonous collectives of our study patients with regard to age and disease. Although the development of physical activity shows only moderate improvements, flexible communication and tailored support could be easily integrated into patients' daily routine. TRIAL REGISTRATION: iPEP study: ClinicalTrials.gov NCT02478996; https://clinicaltrials.gov/ct2/show/NCT02478996 (Archived by WebCite at http://www.webcitation.org/6zL1UmHaW); HELP study: ClinicalTrials.gov NCT02526732; http://www.webcitation.org/6zJjX7d6K (Archived by WebCite at http://www.webcitation.org/6Nch4ldcL); EXDEP study: ClinicalTrials.gov NCT02874833; https://clinicaltrials.gov/ct2/show/NCT02874833 (Archived by WebCite at http://www.webcitation.org/6zJjj7FuA).

Increases in Circulating Cell-Free DNA During Aerobic Running Depend on Intensity and Duration.

PURPOSE: Increases in concentrations of circulating cell-free DNA (cfDNA) have recently been demonstrated to occur in a variety of exhausting and vigorous exercise settings. Here, the authors assessed the association of cfDNA with exercise duration and intensity in a controlled test-retest setting of a regenerative up-to-moderate-level aerobic run. METHODS: In a pretest, the lactate threshold (LT) was determined in 13 participants (range 10.8-13.4 km/h) by using a step-wise incremental running test. The speed of the 2 endurance runs was set to 9.6 km/h for 40 min; for the participants with an LT below the median (12.8 km/h; G1), this was a moderate aerobic run, and for those with an LT above the median, this was a regenerative run (G2). Capillary cfDNA, lactate, and rating of perceived exertion (RPE) were assessed before, every 10 min during, and after the runs. RESULTS: During the last 30 min of the 2 runs, lactate did not increase, whereas cfDNA increased steadily (3.46-fold for G1 and 2.05-fold for G2). Intraclass correlation for cfDNA was high (r = .81, P < .0001) for all runners but higher for male participants (r = .92, P < .0001). The correlations of cfDNA and lactate with RPEs were r = .58 (P < .0001) and r = .32 (P < .05), respectively. CONCLUSIONS: Both duration and level of intensity were significantly associated with accumulation of cfDNA. The correlation with RPE and the high test-retest reliability suggest that cfDNA might be applicable as a marker to monitor individual training load for aerobic and intermittent exercises. Future randomized, controlled, longitudinal training studies will have to reveal the full potential of cfDNA as an exercise-physiology marker.