Cell-free DNA kinetics in response to muscle-damaging exercise: A drop jump study.

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 < 0.01). Elevation of postexercise cfDNA was correlated with both more pronounced low-frequency fatigue (r = -0.52, P = 3.4 × 10-11) and delayed-onset muscle soreness (r = 0.32, P = 0.00019). Levels of cfDNA change in response to severe primary and secondary muscle damage after exercise. Levels of cfDNA exhibit a stronger correlation with variables related to primary muscle damage than to secondary muscle damage, suggesting that cfDNA is a more sensitive marker of acute loss of muscle function than of secondary inflammation or damaged muscle fibres.

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.

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.

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.

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.

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.

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.

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.

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.

Obstructive sleep apnea as a risk factor for primary open angle glaucoma and ocular hypertension in a monocentric pilot study.

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 < 0.0001) with severely lower event rates in the LTG (9.45/h) compared to POAG (22.7/h) and controls (21.9/h; p < 0.0001 and 0.02, respectively). Highly significant differences were found between the four groups regarding AHI (Chi2 = 22, df = 3, p < 0.0001) with significantly lower events per hour in the LTG compared to POAG (Hodges-Lehmann = - 13.8, 95% CI (- 18.6 - - 8.8; p < 0.0001) and to controls (Hodges-Lehmann = 12.1, 95% CI -19.9 - - 2.4; p < 0.02). Severe and moderate OSA was more prevalent in POAG (69.8%) and OH (33.3%) than in LTG (9%). The effect of the glaucoma phenotype on the AHI was more prominent in females (p = 0.0006) than in males (p = 0.011). CONCLUSION: Although physical endpoints, such as MD and IOP, do not correlate with AHI, there was a strong correlation between the POAG and OH clinical glaucoma phenotypes and the AHI. Further studies should investigate the necessity to test routine screening for OSA by HSAT in patients with diagnosed POAG and OH. Besides, some characteristics of LTG differed widely from other glaucoma types and controls. LTG patients had a significantly lower rate of OSA compared to other glaucoma types and even controls. This might be due to a different pathogenesis of LTG. TRIAL REGISTRATION: Retrospectively registered at DRKS ( nr. S00021201 ) on April 9th 2020.

Beyond BMI: waist circumference and social environment is associated with motor performance ability in kindergartners.

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.

Impact of Myocardial Fibrosis on Left Ventricular Function Evaluated by Feature-Tracking Myocardial Strain Cardiac Magnetic Resonance in Competitive Male Triathletes With Normal Ejection Fraction.

BACKGROUND: To analyze the effect of myocardial fibrosis on left ventricular (LV) function evaluated by feature-tracking strain analysis by cine cardiac magnetic resonance (CMR) in competitive male triathletes with normal ejection fraction (EF).Methods and Results:78 asymptomatic male triathletes with >10 weekly training hours (43±11 years) and 28 male age-matched controls were studied by late gadolinium enhancement (LGE) and cine CMR. Global and segmental radial, longitudinal and circumferential strains were analyzed using feature-tracking cine CMR. Focal non-ischemic LGE was observed in 15 of 78 triathletes (19%, LGE+) with predominance in the basal inferolateral segments. LVEF was normal in LGE+ (62±6%) and LGE- triathletes (62±5%, P=0.958). In contrast, global radial strain was lower in LGE+ triathletes at 40±7% compared with LGE- triathletes (45±7%, P<0.05). Reduced segmental radial strain occurred either in LGE+ segments or in directly adjacent segments. Strain analysis revealed regional differences in controls, with the highest radial and longitudinal strain in the inferolateral segments, which were typically affected by fibrosis in LGE+ triathletes. CONCLUSIONS: Reduced global and regional radial strain suggests a negative effect of myocardial fibrosis on LV function in LGE+ triathletes with normal EF. The observed regional differences in controls with the highest radial and longitudinal strain in the inferolateral segments may explain the typical occurrence of fibrosis in this myocardial region in triathletes.

Web-Based Exercise as an Effective Complementary Treatment for Patients With Nonalcoholic Fatty Liver Disease: Intervention Study.

BACKGROUND: Physical inactivity is a major risk factor for nonalcoholic fatty liver disease (NAFLD). Exercise-based prevention interventions for improving cardiorespiratory fitness are a recommended complementary treatment for NAFLD. Achievement of minimally effective physical activity to improve cardiorespiratory fitness among patients typically involves high personal and financial expenses in face-to-face settings. We designed an eHealth approach for patients with NAFLD to improve the cardiorespiratory fitness and report the first results of the HELP (Hepatic Inflammation and Physical Performance in Patients With NASH [nonalcoholic steatohepatitis]) study. OBJECTIVE: We aimed to assess the effectiveness of an 8-week, tailored, Web-based exercise intervention for cardiorespiratory fitness improvement, expressed as peak oxygen uptake (peak volume of oxygen [VO2peak]), in patients with histologically confirmed NAFLD. METHODS: In a 24-month period, 44 patients were enrolled into an 8-week, prospective, single-arm study with 12 weeks of follow-up. After a medical examination and performance diagnostics, a sports therapist introduced the patients to a Web-based platform for individualized training support. Regular individual patient feedback was provided to systematically adapt the weekly exercise schedule, which allowed us to monitor and ensure patient adherence to strength and endurance training and optimize the step-wise progressive exercise load. Exercise progression was based on an a priori algorithm that considered the subjective rate for both perceived exhaustion and general physical discomfort. The VO2peak was assessed at baseline and at the end of the study by spiroergometry. RESULTS: A total of 43 patients completed the intervention with no adverse events. The VO2peak increased significantly by 2.4 mL/kg/min (8.8%; 95% confidence interval [CI]: 1.48-3.27; P<.001) accompanied by a reduction of 1.0 kg in a body weight (95% CI: 0.33-1.58; P=.004) and 1.3 kg in body fat mass (95% CI: 0.27-2.27; P=.01). In an exploratory analysis, step-wise logistic regression analysis revealed low body fat and VO2peak at baseline and the total minutes of endurance training during the intervention as main contributors to a positive change in VO2peak. Our predictive model indicated that the average patient with NAFLD needed 223 min for stabilization of VO2peak and 628 min for average improvement in VO2peak. However, in patients with a VO2peak approximately 20% higher than the average VO2peak, 628 min were only sufficient to stabilize the VO2peak and >40% reduction in the average fat mass would be required to achieve an average outcome. CONCLUSIONS: This is the first study to show that patients with NAFLD can be effectively supported by a Web-based approach, which can increase the VO2peak to a similar extent as face-to-face interventions. Patients with low body fat and low VO2peak benefited the most from our intervention. In terms of future treatment strategies, NAFLD patients with high body fat may particularly benefit from body-fat reduction through a strict nutritional intervention, subsequently enabling a more effective exercise intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02526732; https://clinicaltrials.gov/ct2/show/NCT02526732 (Archived by WebCite at http://www.webcitation.org/74pXhXXfq). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.8607.

Antidoping Science: Important Lessons From the Medical Sciences.

The ineffectiveness of antidoping programs in elite sport, largely due to human and political factors, is leading to a new resolve and greater transparency of antidoping authorities and those stakeholders interested in drug-free sport. The perception by the public, athletes, and the World Anti-Doping Agency (WADA) of antidoping science and current drug testing programs in elite sport varies widely from "ineffective" to "robust and reliable." Here, we discuss why a careful and considered reevaluation of the underlying premise of antidoping science is needed to bring this unique application of predictive/diagnostic science more in line with other areas of medicine. We show how the validity of doping tests are neither "stand-alone figures" generated under ideal laboratory conditions, nor figures that can be used in isolation to support the efficacy of the current drug testing program. Given the consequences of a failed doping test for the athlete, the sport, and multiple stakeholders (e.g., the sponsors), there is a need for transparent decision making to ensure those affected are well informed. We identify in this perspective the minimal essential data on drug testing that should be reported by antidoping laboratories to draw meaningful conclusions about the effectiveness of specific drug testing methods to support antidoping. In the absence of information on the validity of a doping test, it is not possible to plan or conduct "intelligent testing." It is imperative that the prevalence of doping and the likelihood of false-positive doping tests be regularly updated and made available for the wider antidoping research community to explore new approaches that could improve the validity of antidoping tests. True confirmatory testing which requires the use of different analytical technology and ideally an independent sample taken from an athlete with a positive test to transcend the present-day analysis of the B-sample. Indirect biomarkers of doping derived from new "omics"-based approaches may significantly improve the testing strategy. Biomarker molecular signatures are flexible enough to develop "normal ranges" optimized for either test sensitivity or specificity to detect a plethora of doping substances and methods.

Internet-based perioperative exercise program in patients with Barrett's carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomized-controlled trial.

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.

Analgesics use in competitive triathletes: its relationship to doping and on predicting its usage.

The two major objectives of this study were (i) to assess variables that predict the use of analgesics in competitive athletes and (ii) to test whether the use of analgesics is associated with the use of doping. A questionnaire primarily addressing the use of analgesics and doping was distributed among 2,997 triathletes. Binary logistic regression analysis was performed to predict the use of analgesics. Moreover, the randomised response technique (RRT) was used to estimate the prevalence of doping in order to assess whether users of analgesics have a higher potential risk for doping than non-users. Statistical power analyses were performed to determine sample size. The bootstrap method was used to assess the statistical significance of the prevalence difference for doping between users and non-users of analgesics. Four variables from a pool of 16 variables were identified that predict the use of analgesics. These were: "version of questionnaire (English)", "gender (female)", "behaviour in case of pain (continue training)", and "hours of training per week (>12 h/week)". The 12-month prevalence estimate for the use of doping substances (overall estimate 13.0%) was significantly higher in athletes that used analgesics (20.4%) than in those athletes who did not use analgesics (12.4%). The results of this study revealed that athletes who use analgesics prior to competition may be especially prone to using doping substances. The predictors of analgesic use found in the study may be of importance to prepare education material and prevention models against the misuse of drugs in athletes.

Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage.

The role of cell free DNA (cfDNA) has been intensively discussed under various pathological conditions and after acute bouts of exercise. To date, there is still no conclusive evidence concerning the cellular origin of cfDNA and the entire mechanism leading to elevated cfDNA concentrations in human plasma and serum. Here, we investigated the cellular origin of cfDNA in sex-mismatched haematopoietic stem cell transplantation (HSCT) and liver transplantation (LT) patients by determining the relative proportion of Y-chromosomal to total nuclear cfDNA. Total nuclear cfDNA and Y-chromosomal cfDNA concentrations were determined in blood plasma before and after an incremental exercise test via quantitative real-time PCR (qPCR). Female HSCT patients showed high proportions of Y-chromosomal cfDNA. Both total nuclear and Y-chromosomal cfDNA increased significantly and in a highly correlated fashion due to exercise. In male HSCT patients with female donors less than 10% of the cfDNA was of Y-chromosomal origin at any point in time and even though the total amount of cfDNA increased during exercise, no increases in Y-chromosomal DNA could be detected. The percentage of Y-chromosomal cfDNA in female LT patients with male donors was very low and levels remained unchanged during exercise. This indicates that cells not derived from the bone marrow, in this case transplanted liver cells, represented only a minor fraction of cfDNA in blood plasma and were not released during acute physical exercise. Even though many physiological conditions may be altered in transplant patients versus healthy people, our results strongly suggest that cells from the haematopoietic lineage are the main source of cfDNA released during acute bouts of exercise.

Release of bulk cell free DNA during physical exercise occurs independent of extracellular vesicles.

PURPOSE: Strenuous exercise induces a rapid and transient elevation of cell free DNA (cfDNA) concentration in blood plasma. The detection of cfDNA in the presence of plasma nucleases could indicate an association of cfDNA with protective vesicular structures. Several cell types release extracellular vesicles (EVs), including exosomes and shedding microvesicles, which are known to mediate the exchange of proteins and nucleic acids (largely RNA) between cells. Here, we assessed whether EVs play a role in the exercise-dependent release of cfDNA in blood plasma. METHODS: Venous blood collected from healthy volunteers before and after incremental treadmill exercise was separated into vesicular (EV) and soluble fractions. Nuclear and mitochondrial DNA content in plasma supernatants and EV fractions was determined by quantitative real-time PCR (qPCR). RESULTS: We show that the majority of cfDNA is located in the plasma supernatants. Only minute amounts of DNA were observed in the EV-associated fractions including microvesicles and exosomes. Nuclear and mitochondrial DNA species differ in terms of their quantities in the several plasma fractions. CONCLUSIONS: Our results indicate that cfDNA liberated in response to acute physical exercise is not released by vesicular means and circulates in a soluble form in blood plasma which could indicate different biological functions exerted by cfDNA and EVs. The different nature of DNA species in plasma has major implications for the preparation of plasma and other bodily fluids prior to analysis.

Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients.

High levels of cell free DNA (cfDNA) in human blood plasma have been described in patients with autoimmune diseases. The aim of this study was to determine the levels of cfDNA in systemic lupus erythematosus (SLE) patients and to assess fluctuations of cfDNA concentrations compared to the course of disease progression under standard treatment. Therefore, nuclear cfDNA concentrations in plasma were measured in 59 SLE patients and 59 healthy controls. Follow-up blood plasma was collected from 27 of the 59 SLE patients. Patients were characterised by clinical parameters (antinuclear antibodies (ANA), anti-dsDNA-antibodies, C3, C4, and CRP), SLE disease activity index (SLEDAI) and medical therapy. Our results showed that cfDNA concentrations were significantly higher in SLE patients compared to healthy individuals. Levels of cfDNA assessed in serial samples correlated significantly with the medical evaluation of disease activity in SLE patients. Our results could implicate cfDNA as a global marker for disease activity.

Child-caregivers' body weight and habitual physical activity status is associated with overweight in kindergartners.

BACKGROUND: The aim of this study was to examine whether child-caregivers', both parents and kindergarten teachers, health parameters (age, weight status, habitual physical activity score) are significantly associated with the risk of overweight in young children. METHODS: We assessed the individual body mass index standard deviation score in a regional cross-sectional health study and matched a representative sample of 434 kindergartners aged 3 to 6-years with their caregivers' weight and habitual physical activity status. Furthermore, we identified factors associated with the general ability of child-caregivers to identify overweight in children, and the awareness to classify a child within the correct weight category. RESULTS: Our study confirmed most of the known associations between parental anthropometrics and psychosocial factors with childhood overweight and obesity. A significantly higher proportion of boys tended to be overweight or obese (p = 0.027) and parents were more likely to misclassified boys overweight as normal weight (OR: 1.86; 95% CI 1.21-2.86). Adjusted for confounders, logistic regression analysis revealed that kindergarten teachers' weight status (OR: 1.97; 95%-CI: 1.01-3.83) and habitual physical activity scores (OR: 2.32; 95%-CI: 1.10-4.92) were associated with children's weight status. CONCLUSIONS: Kindergarten teachers' weight and habitual physical activity score seem to be new independent risk factors for overweight in kindergartners 3 to 6-years of age. Our results suggest that the psychosocial, non-genetic association of non-parental child-caregivers on children's weight is relatively high and that the association of non-parental child-caregivers warrants further investigation.