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 EVphenotyping 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.

BackgroundDue 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.ObjectiveThe 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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 RegistrationClinicalTrials.gov NCT02874833; https://clinicaltrials.gov/ct2/show/NCT02874833 (Archived by WebCite at http://www.webcitation.org/72ZUUR4tE)

BackgroundAttempts 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.MethodsNine 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.ResultsLactate 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.DiscussionWe 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.

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.

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.