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PurposeWe investigated the cardiovascular individual response to 6 weeks (3×/week) of work-matched within the severe-intensity domain (high-intensity interval training, HIIT) or moderate-intensity domain (moderate-intensity continuous training, MICT). In addition, we analyzed the cardiovascular factors at baseline underlying the response variability.Methods42 healthy sedentary participants were randomly assigned to HIIT or MICT. We applied the region of practical equivalence-method for identifying the levels of responders to the maximal oxygen uptake (V̇O2max) response. For investigating the influence of cardiovascular markers, we trained a Bayesian machine learning model on cardiovascular markers.ResultsDespite that HIIT and MICT induced significant increases in V̇O2max, HIIT had greater improvements than MICT (p < 0.001). Greater variability was observed in MICT, with approximately 50% classified as “non-responder” and “undecided”. 20 “responders”, one “undecided” and no “non-responders” were observed in HIIT. The variability in the ∆V̇O2max was associated with initial cardiorespiratory fitness, arterial stiffness, and left-ventricular (LV) mass and LV end-diastolic diameter in HIIT; whereas, microvascular responsiveness and right-ventricular (RV) excursion velocity showed a significant association in MICT.ConclusionOur findings highlight the critical influence of exercise-intensity domains and biological variability on the individual V̇O2max response. The incidence of “non-responders” in MICT was one third of the group; whereas, no “non-responders” were observed in HIIT. The incidence of “responders” was 11 out of 21 participants in MICT, and 20 out of 21 participants in HIIT. The response in HIIT showed associations with baseline fitness, arterial stiffness, and LV-morphology; whereas, it was associated with RV systolic function in MICT.

Self-reported health problems following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common and often include relatively non-specific complaints such as fatigue, exertional dyspnoea, concentration or memory disturbance and sleep problems. The long-term prognosis of such post-acute sequelae of COVID-19/post-COVID-19 syndrome (PCS) is unknown, and data finding and correlating organ dysfunction and pathology with self-reported symptoms in patients with non-recovery from PCS is scarce. We wanted to describe clinical characteristics and diagnostic findings among patients with PCS persisting for >1 year and assessed risk factors for PCS persistence versus improvement. This nested population-based case-control study included subjects with PCS aged 18-65 years with (n = 982) and age- and sex-matched control subjects without PCS (n = 576) according to an earlier population-based questionnaire study (6-12 months after acute infection, phase 1) consenting to provide follow-up information and to undergo comprehensive outpatient assessment, including neurocognitive, cardiopulmonary exercise, and laboratory testing in four university health centres in southwestern Germany (phase 2, another 8.5 months [median, range 3-14 months] after phase 1). The mean age of the participants was 48 years, and 65% were female. At phase 2, 67.6% of the patients with PCS at phase 1 developed persistent PCS, whereas 78.5% of the recovered participants remained free of health problems related to PCS. Improvement among patients with earlier PCS was associated with mild acute index infection, previous full-time employment, educational status, and no specialist consultation and not attending a rehabilitation programme. The development of new symptoms related to PCS among participants initially recovered was associated with an intercurrent secondary SARS-CoV-2 infection and educational status. Patients with persistent PCS were less frequently never smokers (61.2% versus 75.7%), more often obese (30.2% versus 12.4%) with higher mean values for body mass index (BMI) and body fat, and had lower educational status (university entrance qualification 38.7% versus 61.5%) than participants with continued recovery. Fatigue/exhaustion, neurocognitive disturbance, chest symptoms/breathlessness and anxiety/depression/sleep problems remained the predominant symptom clusters. Exercise intolerance with post-exertional malaise (PEM) for >14 h and symptoms compatible with myalgic encephalomyelitis/chronic fatigue syndrome were reported by 35.6% and 11.6% of participants with persistent PCS patients, respectively. In analyses adjusted for sex-age class combinations, study centre and university entrance qualification, significant differences between participants with persistent PCS versus those with continued recovery were observed for performance in three different neurocognitive tests, scores for perceived stress, subjective cognitive disturbances, dysautonomia, depression and anxiety, sleep quality, fatigue and quality of life. In persistent PCS, handgrip strength (40.2 [95% confidence interval (CI) [39.4, 41.1]] versus 42.5 [95% CI [41.5, 43.6]] kg), maximal oxygen consumption (27.9 [95% CI [27.3, 28.4]] versus 31.0 [95% CI [30.3, 31.6]] ml/min/kg body weight) and ventilatory efficiency (minute ventilation/carbon dioxide production slope, 28.8 [95% CI [28.3, 29.2]] versus 27.1 [95% CI [26.6, 27.7]]) were significantly reduced relative to the control group of participants with continued recovery after adjustment for sex-age class combinations, study centre, education, BMI, smoking status and use of beta blocking agents. There were no differences in measures of systolic and diastolic cardiac function at rest, in the level of N-terminal brain natriuretic peptide blood levels or other laboratory measurements (including complement activity, markers of Epstein-Barr virus [EBV] reactivation, inflammatory and coagulation markers, serum levels of cortisol, adrenocorticotropic hormone and dehydroepiandrosterone sulfate). Screening for viral persistence (PCR in stool samples and SARS-CoV-2 spike antigen levels in plasma) in a subgroup of the patients with persistent PCS was negative. Sensitivity analyses (pre-existing illness/comorbidity, obesity, medical care of the index acute infection) revealed similar findings. Patients with persistent PCS and PEM reported more pain symptoms and had worse results in almost all tests. A limitation was that we had no objective information on exercise capacity and cognition before acute infection. In addition, we did not include patients unable to attend the outpatient clinic for whatever reason including severe illness, immobility or social deprivation or exclusion. In this study, we observed that the majority of working age patients with PCS did not recover in the second year of their illness. Patterns of reported symptoms remained essentially similar, non-specific and dominated by fatigue, exercise intolerance and cognitive complaints. Despite objective signs of cognitive deficits and reduced exercise capacity, there was no major pathology in laboratory investigations, and our findings do not support viral persistence, EBV reactivation, adrenal insufficiency or increased complement turnover as pathophysiologically relevant for persistent PCS. A history of PEM was associated with more severe symptoms and more objective signs of disease and might help stratify cases for disease severity.

In the present study, we aimed to determine the effect of moderate ambient heat stress on exercise‐provoked patterns of “leaky gut” biomarkers and stress markers in well‐trained athletes. Eleven triathletes performed a strenuous 1‐h treadmill run, both under normal ambient conditions (N, 18–21°C) as well as under moderate heat environmental conditions (H, 28–30°C). Core body temperature (Tc), heart rate (HR), and rating of perceived exertion (RPE) significantly increased under both conditions, with significantly higher values during and after the H run. We observed a significant main effect of acute exercise on circulating leukocyte numbers, release of cell‐free human DNA (cfDNA) but not bacterial DNA (bacDNA), and on plasma levels of intestinal fatty‐acid binding protein (I‐FABP), lipopolysaccharide‐binding protein (LBP), endotoxin (LPS), and D‐lactate. Exercising under H conditions accelerated the mobilization of circulating neutrophils and lymphocytes, and significantly affected the release of cfDNA, D‐lactate, I‐FABP, creatinine, and blood potassium levels. Multiple correlation analysis revealed a significant association between Tc, max and exercise‐provoked release of cfDNA (r = 0.583, p = 0.012) as well as with I‐FABP (r = 0.554, p = 0.026). Our data indicate that acute exercising and heat stress may not only affect paracellular but also transcellular intestinal permeability.

Abstract Introduction: Short educational programs prior to metabolic and bariatric surgery (MBS) provide information to prepare patients adequately for surgery and subsequent changes. Our knowledge of the beneficial effects of these programs on stabilizing and improving mental health of patients with obesity awaiting surgery is incomplete. The objective of this study was to assess the effects of a group-based educational program before MBS on three key factors: (i) patients’ mental health, (ii) the program’s perceived helpfulness from the patients’ perspective, and (iii) the effectiveness of delivering the program online via videoconferencing. Methods: Validated questionnaires for anxiety, depression, stress, and quality of life before and after the program were assessed. Additionally, participants’ perspectives of benefits were assessed. Two subgroups, one participating in face-to-face classes, the other participating online via videoconferencing, were compared. Results: Three hundred five patients with obesity waiting for MBS participated in the program. The dropout rate was 3%. On mean average, symptoms of anxiety (−1.1 units [SD 4.6], p < 0.001), depression (−0.9 units [SD 4.6], p < 0.001), and stress (−4.6 units [SD 15.6], p < 0.001) improved, while physical quality of life (+1.7 units [SD 9.7], p = 0.016) and body weight (−0.3 kg [SD 8.7], p = 0.57) remained stable. Patients perceived the program as very beneficial. The results were similar between delivery methods (face-to-face vs. videoconferencing). Conclusion: The educational program proved to be effective in bridging the gap in preoperative preparation while also stabilizing participants’ mental health. In addition, participants perceived the program as supportive. Online participation via video conferencing can be offered as an equivalent option to face-to-face classes.

microRNAs (miRs) have been proposed as a promising new class of biomarkers in the context of training adaptation. Using microarray analysis, we studied skeletal muscle miR patterns in sedentary young healthy females (n = 6) before and after a single submaximal bout of endurance exercise (‘reference training’). Subsequently, participants were subjected to a structured training program, consisting of six weeks of moderate-intensity continuous endurance training (MICT) and six weeks of high-intensity interval training (HIIT) in randomized order. In vastus lateralis muscle, we found significant downregulation of myomiRs, specifically miR-1, 133a-3p, and -5p, -133b, and -499a-5p. Similarly, exercise-associated miRs-23a-3p, -378a-5p, -128-3p, -21-5p, -107, -27a-3p, -126-3p, and -152-3p were significantly downregulated, whereas miR-23a-5p was upregulated. Furthermore, in an untargeted approach for differential expression in response to acute exercise, we identified n = 35 miRs that were downregulated and n = 20 miRs that were upregulated by factor 4.5 or more. Remarkably, KEGG pathway analysis indicated central involvement of this set of miRs in fatty acid metabolism. To reproduce these data in a larger cohort of all-female subjects (n = 29), qPCR analysis was carried out on n = 15 miRs selected from the microarray, which confirmed their differential expression. Furthermore, the acute response, i.e., the difference between miR concentrations before and after the reference training, was correlated with changes in maximum oxygen uptake (V̇O2max) in response to the training program. Here, we found that miRs-199a-3p and -19b-3p might be suitable acute-response candidates that correlate with individual degrees of training adaptation in females.

The evaluation of the maximal oxygen uptake (V˙O2max) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention (V˙O2max), also do not improve in other health‐related parameters. We aimed to investigate the cardiovascular and metabolic adaptations (i.e., performance, body composition, blood pressure, vascular function, fasting blood markers, and resting cardiac function and morphology) to exercise training among participants who showed different levels of V˙O2max responsiveness. Healthy sedentary participants engaged in a 6‐week exercise training program, three times a week. Our results showed that responders had a greater increase in peak power output, second lactate threshold, and microvascular responsiveness, whereas non‐responders had a greater increase in cycling efficiency. No statistical differences were observed in body composition, blood pressure, fasting blood parameters, and resting cardiac adaptations. In conclusion, our study showed, for the first time, that in addition to the differences in the V˙O2max, a greater increase in microvascular responsiveness in responders compared to non‐responders was observed. Additionally, responders and non‐responders did not show differences in the adaptations on metabolic parameters. There is an increasing need for personalized training prescription, depending on the target clinical outcome. The evaluation of the maximal oxygen uptake (V˙O2max) following exercise training is the classical assessment of training effectiveness. Research has lacked in investigating whether individuals that do not respond to the training intervention (V˙O2max), also do not improve in other health‐related parameters. Our results showed that responders had a greater increase than non‐responders in peak power output, second lactate threshold, and microvascular responsiveness, whereas non‐responders had a greater increase in cycling efficiency than responders.

Long- and post-COVID syndrome (PCS) affect at least 65 million individuals globally, with an estimated incidence of 10% among over 651 million documented cases of SARS-CoV-2 infection. PCS impacts nearly every organ system, posing significant challenges for healthcare systems and patients. Despite this, effective guidelines for multimodal training or rehabilitation remain absent. The app-based physical intervention for long- and post-COVID treatment (A PILOT) study is a prospective, multicentre, two-armed, randomised controlled trial to evaluate the effectiveness of an app-based multimodal training intervention in patients with PCS. 100 participants will be randomly assigned to an intervention group (IG) or a control group (CG). Over 2 months, the IG will follow a standardised app-based intervention programme incorporating breathing exercises, endurance and strength training and progressive muscle relaxation. The CG will adhere to general WHO exercise recommendations during the waiting period and gain access to the app after the study concludes. Comprehensive assessments, including physical examinations, blood tests, psychological questionnaires, transthoracic echocardiography, electrocardiography and cardiopulmonary exercise testing, will be conducted pre- and post-intervention. The primary endpoints are the effects of app-based multimodal training on physical performance, neurocognitive function and health-related quality of life. Secondary endpoints include mental health outcomes (eg, depression, perceived stress, sleep quality and daytime sleepiness), echocardiographic and anthropometric measures and alterations in inflammatory markers and metabolites of the kynurenine pathway. This study aims to provide critical insights into structured app-based programmes, potentially establishing a framework for improving recovery in PCS patients.

Small, non‐coding RNAs (microRNAs) have been shown to regulate gene expression in response to exercise in various tissues and organs, thus possibly coordinating their adaptive response. Thus, it is likely that differential microRNA expression might be one of the factors that are responsible for different training responses of different individuals. Consequently, determining microRNA patterns might be a promising approach toward the development of individualized training strategies. However, little is known on (1) microRNA patterns and their regulation by different exercise regimens and (2) possible correlations between these patterns and individual training adaptation. Here, we present microarray data on skeletal muscle microRNA patterns in six young, female subjects before and after six weeks of either moderate‐intensity continuous or high‐intensity interval training on a bicycle ergometer. Our data show that n = 36 different microRNA species were regulated more than twofold in this cohort (n = 28 upregulated and n = 8 downregulated). In addition, we correlated baseline microRNA patterns with individual changes in VO2max and identified some specific microRNAs that might be promising candidates for further testing and evaluation in the future, which might eventually lead to the establishment of microRNA marker panels that will allow individual recommendations for specific exercise regimens. Using microarrays and qPCR analysis, we studied microRNA patterns in skeletal muscle in healthy subjects undergoing two different six‐week exercise programs. We identified several miRNAs that had not been implicated in exercise adaptation before. In addition, our data suggest that exercise‐induced changes in microRNA patterns are dependent on exercise type and also on individual background, a finding that suggests that microRNAs might serve as biomarkers for the development of individualized training regimens in the future.

“Athlete’s heart” is characterized by an increase in ventricular chamber sizes and myocardial mass (MM), and is mainly observed in endurance athletes. At present, it remains unclear whether cardiac adaptations in long-distance runners differ from those in triathletes. Twenty male triathletes (mean age 38.7 ± 6.2 years) and 20 male marathon runners (mean age 44.1 ± 7.9) underwent cardiac magnetic resonance imaging to calculate left and right ventricular end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and MM. Late-enhancement (LE) imaging was used to exclude structural alterations or myocardial scarring. EDV, ESV, SV, and EF for the left and right ventricles, as well as MM, did not differ between long-distance runners and triathletes, although the weekly training volume was significantly higher in triathletes (17.05 vs 9.95 h/week, P < 0.0001). There was a significant correlation between weekly training volume and right and left EDV, right and left ESV as well as MM within the study group. Myocardial LE was absent in all athletes. Highly trained male long-distance runners and triathletes have comparable cardiac parameters. However, the extent of physical training seems to be associated with the degree of cardiac adaptation in endurance athletes. The absence of LE supports the idea that athlete’s heart is a nonpathological adaptation of the cardiovascular system.

Intensive endurance training can induce abnormal ECG patterns at rest. These alterations are differentiated into minor, mildly or distinctly abnormal ECG patterns. Echocardiographic data imply a correlation between the extent of these alterations and cardiac parameters like cardiac volume or wall thickness. In comparison to echocardiography, cardiac magnetic resonance imaging (MRI) is characterized by high reproducibility and accuracy. The aim of this study was to investigate the correlation between ECG alterations and cardiac parameters in highly trained asymptomatic male endurance athletes as assessed using cardiac MRI. Forty-five asymptomatic male endurance athletes (mean age 40 ± 8.9 years., range 19–59 years., 13 ± 5 h of training per week) underwent a cardiac MRI examination in addition to a resting ECG. Based on the ECG patterns at rest, the athletes were divided into groups with normal or minor (group 1) and mild or distinct (group 2) alterations. Steady-state free-precession cine MRI was used to calculate left and right ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and myocardial mass (MM). Late enhancement imaging was used to exclude structural alterations or myocardial scarring. Athletes in group 1 and 2 did not differ significantly in terms of age, height, body weight, body mass index or hours of training per week. Athletes with mildly or distinctly abnormal ECG patterns showed a significantly higher MM than athletes with minor ECG alterations at rest or normal resting ECG values (156.4 ± 18.4 g vs. 140.5 ± 20.0 g; p  = 0.0103). The differences persisted when the values were corrected for body surface area (80.0 ± 7.4 g/m² vs. 73.4 ± 8.3 g; p  = 0.0093). All other assessed cardiac parameters did not differ between the two groups. Pathological myocardial enhancement was detected only in one patient with a minor abnormal ECG. Male asymptomatic endurance athletes with mildly or distinctly abnormal ECG patterns at rest are characterized by a higher myocardial mass than comparable athletes with minor alterations or normal ECG at rest. Thus, the extent of ECG-abnormalities seems to be mainly the result of an increase in myocardial mass. Additionally, the absence of mild or distinct ECG alterations does not exclude the presence of pathological late gadolinium enhancement.