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PURPOSE: Cardiopulmonary exercise testing (CPET) is considered the gold standard for assessing cardiorespiratory fitness. To ensure consistent performance of each test, it is necessary to adapt the power increase of the test protocol to the physical characteristics of each individual. This study aimed to use machine learning models to determine individualized ramp protocols based on non-exercise features. We hypothesized that machine learning models will predict peak oxygen uptake ( V Ë O2peak) and peak power output (PPO) more accurately than conventional multiple linear regression (MLR). METHODS: The cross-sectional study was conducted with 274 (â168, â106) participants who performed CPET on a cycle ergometer. Machine learning models and multiple linear regression were used to predict V Ë O2peak and PPO using non-exercise features. The accuracy of the models was compared using criteria such as root mean square error (RMSE). Shapley additive explanation (SHAP) was applied to determine the feature importance. RESULTS: The most accurate machine learning model was the random forest (RMSE: 6.52 ml/kg/min [95% CI 5.21-8.17]) for V Ë O2peak prediction and the gradient boosting regression (RMSE: 43watts [95% CI 35-52]) for PPO prediction. Compared to the MLR, the machine learning models reduced the RMSE by up to 28% and 22% for prediction of V Ë O2peak and PPO, respectively. Furthermore, SHAP ranked body composition data such as skeletal muscle mass and extracellular water as the most impactful features. CONCLUSION: Machine learning models predict V Ë O2peak and PPO more accurately than MLR and can be used to individualize CPET protocols. Features that provide information about the participant's body composition contribute most to the improvement of these predictions. TRIAL REGISTRATION NUMBER: DRKS00031401 (6 March 2023, retrospectively registered).
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While pre-post differences in immune cell mobilization after acute aerobic exercise are well investigated, less is known about when and to what extent immune cells are mobilized during acute aerobic exercise. This experimental trial aimed to investigate the detailed kinetics of circulating immune cells in twelve healthy adults (n=6 females) who completed a 40-min aerobic exercise bout at 60% of the participants' VÌO2peak on a bicycle ergometer. Cellular inflammation markers and sex-dependent differences in circulating immune cells were analyzed. Blood samples were taken immediately before, after warm-up, during exercise after 5 min, 10 min, 15 min, 30 min, 40 min (cessation), and 60 min post exercise. Significant increases in leukocytes (p<0.001), lymphocytes (p<0.001), neutrophils (p=0.003) and platelets (p=0.047) can be observed after 5 min of exercise. The cellular inflammation markers show significant alterations only post exercise. Significant sex differences were observed for neutrophils (p=0.049) and neutrophil-to-lymphocyte ratio (p=0.007) one hour post exercise. These results indicate that i) leukocytes are already mobilized after 5 min of moderate-to-vigorous aerobic exercise, ii) the magnitude of exercise induced leukocyte mobilization is dependent on exercise duration, iii) integrative cellular inflammation markers are only altered after exercise cessation, and iv) the observed effects might be sex-dependent.
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The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% VÌo2peak, and 3-min intervals at 50% VÌo2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.NEW & NOTEWORTHY The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.
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Ácido Quinurénico , Quinurenina , Leucocitos Mononucleares , Receptores de Hidrocarburo de Aril , Receptores de Hidrocarburo de Aril/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Quinurenina/metabolismo , Masculino , Animales , Ácido Quinurénico/metabolismo , Ácido Quinurénico/sangre , Ejercicio Físico/fisiología , Ratones , Ratones Endogámicos C57BL , Humanos , Condicionamiento Físico Animal/fisiología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Transducción de Señal , Triptófano/metabolismo , Triptófano/sangreRESUMEN
Despite substantial evidence emphasizing the pleiotropic benefits of exercise for the prevention and treatment of various diseases, the underlying biological mechanisms have not been fully elucidated. Several exercise benefits have been attributed to signaling molecules that are released in response to exercise by different tissues such as skeletal muscle, cardiac muscle, adipose, and liver tissue. These signaling molecules, which are collectively termed exerkines, form a heterogenous group of bioactive substances, mediating inter-organ crosstalk as well as structural and functional tissue adaption. Numerous scientific endeavors have focused on identifying and characterizing new biological mediators with such properties. Additionally, some investigations have focused on the molecular targets of exerkines and the cellular signaling cascades that trigger adaption processes. A detailed understanding of the tissue-specific downstream effects of exerkines is crucial to harness the health-related benefits mediated by exercise and improve targeted exercise programs in health and disease. Herein, we review the current in vivo evidence on exerkine-induced signal transduction across multiple target tissues and highlight the preventive and therapeutic value of exerkine signaling in various diseases. By emphasizing different aspects of exerkine research, we provide a comprehensive overview of (i) the molecular underpinnings of exerkine secretion, (ii) the receptor-dependent and receptor-independent signaling cascades mediating tissue adaption, and (iii) the clinical implications of these mechanisms in disease prevention and treatment.
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Terapia por Ejercicio , Músculo Esquelético , Transducción de Señal , Humanos , Músculo Esquelético/metabolismo , Ejercicio Físico , Animales , Tejido Adiposo/metabolismoRESUMEN
BACKGROUND: B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins. Exercise alters B cell counts and immunoglobulin levels, but evidence-based conclusions on potential benefits for adaptive immunity are lacking. This systematic review assessed current literature on the impact of acute exercise and exercise training on B cells, immunoglobulins, and markers of secretory immunity in human biofluids. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, MEDLINE, Web of Science, and Embase were searched on March 8, 2023. Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions, immunoglobulin levels, salivary flow rate, or secretory immunoglobulin A secretion rate were included. Quality and reporting of exercise training studies was assessed using the Tool for the Assessment of Study Quality and reporting in Exercise. Study characteristics, outcome measures, and statistically significant changes were summarized tabularly. RESULTS: Of the 67 eligible studies, 22 applied acute exercise and 45 applied exercise training. All included outcomes revealed significant alterations over time in acute exercise and exercise training context, but only a few investigations showed significant differences compared to control conditions. Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training. CONCLUSION: B cell-related outcomes are altered by acute exercise and exercise training, but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities. Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.
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Introduction: Based on theoretical models, physical activity has been introduced as a promoting method to mitigate the disease severity, fatigue and relapse rate in multiple sclerosis. The primary objective of the study was to investigate the relation between self-reported physical activity level and disease severity, fatigue and relapse rate in persons with relapsing remitting multiple sclerosis (RRMS). Methods: A survey was offered to persons with RRMS from March 2019 to August 2021 (n = 253). Physical activity level, fatigue and disease severity were determined using the Godin Leisure-Time Questionnaire (GLTEQ), the Patient Determined Disease Steps (PDDS) scale and the Fatigue Scale for Motor and Cognitive Functions (FSMC). Additionally, participants' relapse rate was recorded. Results: Bivariate correlations revealed an inverse relation between physical activity level and PDDS (ρ = -0.279; p < 0.001) as well as between physical activity and FSMC (r = -0.213, p < 0.001), but not between physical activity and relapse rate (r = 0.033, p > 0.05). Multiple linear regression analyses explained 12.6% and 5.2% of the variance of PDDS and FSMC. Conclusion: Our findings confirm a relation between self-reported physical activity, disease severity and fatigue in persons with RRMS. However, self-reported physical activity level does not seem to affect the annualised relapse rate.
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Nicotinamide adenine dinucleotide (NAD+ ) is an evolutionarily highly conserved coenzyme with multi-faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD+ levels are a shared characteristic of various diseases and aging per se, several NAD+ -boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD+ homeostasis through metabolic adaption to chronically recurring states of increased energy demand. In this review we discuss the impact of acute exercise and exercise training on tissue-specific NAD+ metabolism of rodents and humans to highlight the potential value as NAD+ -boosting strategy. By interconnecting results from different investigations, we aim to draw attention to tissue-specific alterations in NAD+ metabolism and the associated implications for whole-body NAD+ homeostasis. Acute exercise led to profound alterations of intracellular NAD+ metabolism in various investigations, with the magnitude and direction of changes being strongly dependent on the applied exercise modality, cell type, and investigated animal model or human population. Exercise training elevated NAD+ levels and NAD+ metabolism enzymes in various tissues. Based on these results, we discuss molecular mechanisms that might connect acute exercise-induced disruptions of NAD+ /NADH homeostasis to chronic exercise adaptions in NAD+ metabolism. Taking this hypothesis-driven approach, we hope to inspire future research on the molecular mechanisms of exercise as NAD+ -modifying lifestyle intervention, thereby elucidating the potential therapeutic value in NAD+ -related pathologies.
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Epigénesis Genética , NAD , Animales , Humanos , NAD/metabolismo , Envejecimiento/metabolismo , Metabolismo Energético , HomeostasisRESUMEN
The integrative immune markers neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR) and systemic immune inflammation index (SII) are established markers in clinical patient care. Adoption of these markers in elite athletics might prove beneficial for monitoring training and health. Blood samples of 195 healthy national Olympic squad athletes were collected before a graded bicycle-ergometric exercise test until complete exhaustion. Measurements included white blood cells, lymphocytes and platelets, allowing for the calculation of the integrative immune markers. Correlations between athlete characteristics (sex, age, sporting discipline, training experience, training volume) and integrative immune marker-values were assessed. In a subgroup analysis a second blood sample was collected from 25 athletes at 1 minute after exercise test to assess its effect on the immune marker levels.An inverse correlation between peak power output and SII-level (Pearson correlation coefficient=-.270, p<.001) and NLR-level (Pearson correlation coefficient=-.249, p<.001) was found. Athletes with higher aerobic fitness had significantly lower values of SII and PLR compared to athletes with lower aerobic fitness. An elevated SII (p=.003) and a reduced PLR (p=.001) was documented as acute response to the exercise test. The integrative immune markers might be a promising tool for monitoring training and health in elite athletes.
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Plaquetas , Linfocitos , Humanos , Biomarcadores , Leucocitos , Inflamación , Neutrófilos , Atletas , Estudios RetrospectivosRESUMEN
Physical performance could be negatively affected by sleep deficiency and fatigue. The present study assesses the role of sleep quality, fatigue and motivation on cardiovascular performance (VO2peak, Wmax, and HRmax) in a sample of active young subjects. The current study is a cross-sectional design. Ninety-six university students (males 54.2%; 21.5 ± 2.9 yrs) completed an incremental exercise test on a bicycle ergometer. Sleep, fatigue, and motivation were assessed with the Pittsburgh Sleep Quality Index and two visual analogue scales, respectively. Differences in VO2peak, Wmax, HRmax, self-perceived fatigue and motivation were compared between good and bad sleepers and sleep duration >/<7.5 h, while regression analysis defined the predictors of VO2peak, Wmax, and HRmax. In the male sample, good and bad sleepers' differences were significant only for self-perceived fatigue (p = 0.04). The female sample showed no statistically significant differences between good and bad sleepers and different sleep durations. In the male sample, linear regression analysis showed a significant inverse correlation between Wmax and the PSQI score (-0.4, p = 0.004). The stepwise regression model indicated that sleep (ß = -0.3, p = 0.02) was a significant predictor of VO2peak in males accounting for 20% of the variance, whereas physical performance seems more affected by fatigue (ß = -0.4, p = 0.03) in females. In conclusion, chronic inadequate and self-reported sleep quality seems to be one of the factors compromising cardiovascular performance in males.
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Trastornos del Sueño-Vigilia , Sueño , Estudios Transversales , Fatiga , Femenino , Voluntarios Sanos , Humanos , MasculinoRESUMEN
BACKGROUND: A moderate to high level of physical activity, including regular exercise, represents an established behavioral and rehabilitative approach for persons with multiple sclerosis (pwMS). Although being increasingly proposed to limit disease activity and progression, high-quality evidence is lacking. OBJECTIVE: The objective of the study is to provide valuable information for MS clinicians and researchers by systematically evaluating the current state of evidence (i) whether exercise interventions affect established clinical measures of disease activity and progression in pwMS (i.e., EDSS, relapse rate, lesion load, brain volume, MSFC) and (ii) how the physical activity and fitness level interact with these measures. METHODS: Literature search was conducted in MEDLINE, EMBASE, CINAHL, and SPORTDiscus. Evaluation of evidence quality was done based on standards published by The American Academy of Neurology. RESULTS: It is likely that exercise improves the MSFC score, whereas the EDSS score, lesion load, and brain volume are likely to remain unchanged over the intervention period. It is possible that exercise decreases the relapse rate. Results from cross-sectional studies indicate beneficial effects of a high physical activity or fitness level on clinical measures which, however, is not corroborated by high evidence quality. CONCLUSIONS: A (supportive) disease-modifying effect of exercise in pwMS cannot be concluded. The rather low evidence quality of existing RCTs underlines the need to conduct more well-designed studies assessing different measures of disease activity or progression as primary end points. A major limitation is the short intervention duration of existing studies which limits meaningful exercise-induced effects on most disability measures. Findings from cross-sectional studies are difficult to contextualize regarding clinical importance due to their solely associative character and low evidence quality. PROSPERO REGISTRATION NUMBER: CRD42020188774.
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Esclerosis Múltiple , Estudios Transversales , Ejercicio Físico , Humanos , Esclerosis Múltiple/terapia , Aptitud Física , RecurrenciaRESUMEN
PURPOSE: Prolonged periods of intense cognitive activity lead to a state of mental exhaustion. While widespread strategies to recover from mental exhaustion (i.e., watching TV) are non-effective, aerobic exercise seems to be a promising approach. This can be explained by the acute and chronic aerobic exercise-induced benefits on the central nervous system. METHODS: This study investigated the potential of a single bout of moderate aerobic exercise (65-75% of each participants' individual VËO2peak) to recover from experimentally induced mental exhaustion. A randomized controlled trial on healthy adults (N = 99) was conducted. They performed 60 min of a cognitively demanding test battery, in order to induce mental exhaustion. Subsequently, they were randomized to one of three treatments: 30 min of moderate aerobic exercise on a cycle ergometer, 30 min of a simple lower body stretching routine (= active control treatment) or watching a popular sitcom (= passive control treatment). Cognitive flexibility performance, mood, tiredness, restlessness, self-perceived cognitive capacity, and motivation were assessed before and after treatment. RESULTS: The empirical results showed that moderate aerobic exercise led to a better recovery for cognitive flexibility (mean difference divided by pooled standard deviation, Cohen's d= 0.737), mood (d= 0.405), tiredness (d= 0.480), self-perceived cognitive capacity (d= 0.214), and motivation (d= 0.524) compared to active control treatment. Moderate aerobic exercise was also more effective than passive control treatment (d= 0.102 - 0.286) with the exemption of tiredness (d= 0.015) and restlessness (d = -0.473). CONCLUSION: In conclusion, this study suggests that a single bout of acute aerobic exercise supports regeneration of cognitive flexibility performance and of subjective well-being. This holds true not just compared to artificial active control treatment but also compared to widespread leisure time activity, namely watching TV.
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Terapia por Ejercicio , Calidad de Vida , Adulto , Ejercicio Físico , Fatiga , Humanos , Fatiga MentalRESUMEN
INTRODUCTION: The objective of this systematic review is to explore the application and reporting of (i) the principles of exercise training in exercise trials, (ii) the components of exercise prescription, and (iii) the adherence towards the prescribed programmes in randomised controlled trials (RCTs) in persons with multiple sclerosis (pwMS). METHODS: The MEDLINE, CINAHL, SPORTDiscus, PubMed and Embase electronic databases were searched from 1 January 2000 to 16 October 2020. RCTs comprising at least 3 weeks of aerobic and/or resistance exercise intervention in pwMS that reported at least one physiological outcome and were published in peer-reviewed journals were eligible for inclusion. RESULTS: Out of 52 RCTs included in this review, 58 intervention arms were examined. None applied more than four principles of exercise training. Specificity was addressed by 85%, progression by 33%, overload by 59%, initial values by 26%, reversibility by 0% and diminishing returns by 2% of trials. Fifty-two percent of trials reported all components of exercise prescription, and 3% of trials reported the level of adherence to the prescribed exercise. CONCLUSION: This systematic review reveals that exercise training principles were not respected in the majority of included RCTs. The weak quality of reported exercise interventions limits the interpretation of the studies' results and potentially leads to an underestimation of 'exercise as medicine' in pwMS. Also, the vague descriptions of exercise prescription and adherence impede the reproducibility of results. Future studies must attend to all principles of exercise training and provide transparent information on the prescribed and performed programmes to develop specific and valid exercise recommendations for pwMS. SYSTEMATIC REVIEW REGISTRATION: CRD42020162671, 28/04/2020, PROSPERO.
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Exercise is described to provoke enhancements of cardiorespiratory fitness in persons with Multiple Sclerosis (pwMS). However, a high inter-individual variability in training responses has been observed. This analysis investigates response heterogeneity in cardiorespiratory fitness following high intensity interval (HIIT) and moderate continuous training (MCT) and analyzes potential predictors of cardiorespiratory training effects in pwMS. 131 pwMS performed HIIT or MCT 3-5x/ week on a cycle ergometer for three weeks. Individual responses were classified. Finally, a multiple linear regression was conducted to examine potential associations between changes of absolute peak oxygen consumption (absolute ∆VÌO2peak/kg), training modality and participant's characteristics. Results show a time and interaction effect for ∆VÌO2peak/kg. Absolute changes of cardiorespiratory responses were larger and the non-response proportions smaller in HIIT vs. MCT. The model accounting for 8.6% of the variance of ∆VÌO2peak/kg suggests that HIIT, younger age and lower baseline fitness predict a higher absolute ∆VÌO2peak/kg following an exercise intervention. Thus, this work implements a novel approach that investigates potential determinants of cardiorespiratory response heterogeneity within a clinical setting and analyzes a remarkable bigger sample. Further predictors need to be identified to increase the knowledge about response heterogeneity, thereby supporting the development of individualized training recommendations for pwMS.
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Capacidad Cardiovascular , Entrenamiento de Intervalos de Alta Intensidad , Esclerosis Múltiple , Consumo de Oxígeno , Ejercicio Físico , Humanos , Modelos Lineales , Esclerosis Múltiple/terapiaRESUMEN
Over the last decades the cellular immune inflammation markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII = NLR × platelets) have emerged in clinical context as markers of disease-related inflammation and are now widely appreciated due to their integrative character. Transferring these clinically established inflammation markers into exercise physiology seems highly beneficial, especially due to the low temporal, financial and infrastructural resources needed for assessment and calculation. Therefore, the aim of this review is to summarize evidence on the value of the integrative inflammation markers NLR, PLR and SII for depiction of exercise-induced inflammation and highlight potential applications in exercise settings. Despite sparse evidence, multiple investigations revealed responsiveness of the markers to acute and chronic exercise, thereby opening promising avenues in the field of exercise physiology. In performance settings, they might help to infer information for exercise programming by reflecting exercise strain and recovery status or periods of overtraining and increased infection risk. In health settings, application involves the depiction of anti-inflammatory effects of chronic exercise in patients exhibiting chronic inflammation. Further research should, therefore, focus on establishing reference values for these integrative markers in athletes at rest, assess the kinetics and reliability in response to different exercise modalities and implement the markers into clinical exercise trials to depict anti-inflammatory effects of chronic exercise in different patient collectives.
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Biomarcadores/sangre , Inflamación/inmunología , Esfuerzo Físico/inmunología , Humanos , Recuento de Linfocitos , Neutrófilos , Recuento de Plaquetas , Valores de Referencia , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To examine acute (single-bout) and training effects of high-intensity interval training (HIIT) vs standard exercise therapy (moderate continuous training [MCT]) on plasma neurofilament light chain (pNfL) and kynurenine (KYN) pathway of tryptophan degradation metabolites in persons with multiple sclerosis (pwMS). METHODS: Sixty-nine pwMS (Expanded Disability Status Scale score 3.0-6.0) were randomly assigned to a HIIT or an MCT group. Changes in pNfL and KYN pathway metabolites measured in blood plasma were assessed before, after, and 3 hours after the first training session as well as after the 3-week training intervention. RESULTS: Acute exercise reduced pNfL and increased the KYN pathway flux toward the neuroprotective kynurenic acid (KA). Changes in pNfL correlated positively with changes in KA and negatively with the quinolinic acid-to-KA ratio. HIIT consistently led to greater effects than MCT. Following the 3-week training intervention, the KYN pathway was activated in HIIT compared with MCT. CONCLUSION: Future studies and clinical assessments of pNfL should consider acute exercise as confounding factor for measurement reliability. Moreover, exercise-induced KYN pathway rerouting might mediate neuroprotection, potentially underlying the benefits in rehabilitation for pwMS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that acute HIIT diminishes pNfL and increases KA levels, and 3 weeks of HIIT activate the KYN pathway in pwMS. TRIAL REGISTRATION INFORMATION: Clinical trial registration number: NCT03652519.
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Terapia por Ejercicio/métodos , Quinurenina/sangre , Esclerosis Múltiple/terapia , Proteínas de Neurofilamentos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Triptófano/sangreRESUMEN
BACKGROUND: Persons with multiple sclerosis (PwMS) often have reduced aerobic capacity and report fatigue as the most disabling symptom impacting their health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for successful management of symptoms, although there is little supporting evidence. The aim of this study is to evaluate the effect of a multimodal therapy approach, including endurance training and patient education, during a three-week inpatient rehabilitation stay, on HRQoL in PwMS at six months follow-up. Inpatient energy management education (IEME) + high-intensity interval training (HIIT) will be compared with progressive muscle relaxation (PMR) + moderate continuous training (MCT). METHODS: This study has a two-armed single-blind randomized controlled superiority trial design. One hundred six PwMS-related fatigue (relapsing-remitting or chronic progressive phenotypes; Expanded Disability Status Scale (EDSS) ≤ 6.5) will be recruited at the Valens clinic, Switzerland, and randomized into either an experimental (EG) or a control group (CG). EG: participants will perform IEME twice and HIIT three times per week during the three-week rehabilitation stay. IEME is a group-based intervention, lasting for 6.5 h over three weeks. HIIT contains of five 1.5-min high-intensive exercise bouts on a cycle ergometer at 95-100% of peak heart rate (HRpeak), followed by active breaks of unloaded pedalling for 2 min to achieve 60% of HRpeak. CG: participants will perform PMR twice and MCT three times per week during the three-week rehabilitation stay, representing local usual care. PMR consists of six 1-h relaxation group sessions. MCT consists of 24-min continuous cycling at 65% of HRpeak. The primary outcome is HRQoL (Physical and Mental Component Summaries of the Medical Outcome Study 36-item Short Form Health Survey; SF-36), measured at entry to the clinic (baseline, T0), three weeks after T0 (T1) and at four (T2) and six (T3) months after T0. Secondary outcomes comprise cardiorespiratory fitness, inflammatory markers (measured at T0 and T1), fatigue, mood, self-efficacy, occupational performance, physical activity (measured at T0, T1, T2 and T3) and behaviour changes in energy management (measured at T2 and T3). DISCUSSION: This study will provide detailed information on a multimodal therapy approach to further improve rehabilitation for PwMS. TRIAL REGISTRATION: This trial was prospectively registered at ClinicalTrials.gov ( NCT04356248 ; 22 April 2020).
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Entrenamiento Autogénico/métodos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Esclerosis Múltiple/rehabilitación , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Terapia por Ejercicio/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Método Simple Ciego , Resultado del TratamientoRESUMEN
PURPOSE: Physical activity promises to reduce disease-related symptoms and therapy-related side effects in patients suffering from aggressive lymphoma (L) or acute leukemia (AL). For an efficient training program, determination of patients' physical capacity with a purposive exercise test is crucial. Here, we evaluated the feasibility and suitability of a graded exercise test (GXT) frequently applied in patients suffering from solid tumors by assessing whether patients achieved criteria for maximal exercise testing according to the American College of Sports Medicine (ACSM). METHODS: The GXT was performed by 51 patients with an aggressive L or AL prior to the start or in the earliest possible phase of high-dose chemotherapy, following a recommended protocol for cancer patients, starting at 20 Watts (W), with an increase of 10 W/min until volitional exhaustion. Subsequently, we investigated whether the following ACSM criteria were fulfilled: (1) failure of heart rate to increase despite increasing workload, (2) post-exercise capillary lactate concentration ≥ 8.0 mmol L-1, (3) rating of perceived exertion at exercise cessation > 17 on the 6-20 Borg Scale. RESULTS: Out of 51 patients, two, six, and 35 participants met the first, second, and third criterion, respectively. No relevant relationships between the completion of the criteria and patients' characteristics (e.g., gender, age) were found. CONCLUSION: Although results of this study suggest a general feasibility of the applied GXT, the ACSM criteria were not met by the majority of the participants. Therefore, this study raises doubts about the suitability of the GXT protocol and the ACSM criteria for this group of patients.
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Prueba de Esfuerzo/métodos , Ejercicio Físico/fisiología , Neoplasias Hematológicas/diagnóstico , Adolescente , Adulto , Anciano , Estudios Transversales , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: The programmed cell death protein 1 (PD-1) has become a promising target in cancer immunotherapy. PD-1 expression of CD8+ T-cells may be increased via the exploitation of aryl hydrocarbon receptor (AhR) signaling with kynurenine (KYN) as a ligand. Since exercise affects KYN metabolism, we exploratory investigated the influence of acute exercise bouts on AhR and PD-1 levels of CD8+ T-cells. METHOD: In this study, 24 healthy males (age: 24.6 ± 3.9 years; weight 83.9 ± 10.5 kg; height: 182.4 ± 6.2 cm) completed a single bout of endurance (EE) and resistance exercise (RE) in a randomly assigned order on separate days. Blood samples were drawn before (t0), after (t1), and 1 h after (t2) both conditions. T-cell populations, the level of cytoplasmic AhR, and surface PD-1 were assessed by flow cytometry. RESULTS: T-cell populations changed over time, indicated by an increase in the absolute numbers of CD3+ lymphocytes after EE (p < .001) and RE (p = .036) and in PD-1+ CD8+ T-cells after EE (p = .021). Proportions of T-cell populations changed only after EE (t0-t2: p = .029; t1-t2: p = .006). The level of cytoplasmic AhR decreased immediately after exercise in both exercise conditions (EE: p = .009; RE: p = .036). The level of surface PD-1 decreased 1 h after EE (p = .005). CONCLUSION: We analyzed the level of surface PD-1 and cytoplasmic AhR following acute physical exercise for the first time. Especially EE was observed to impact both AhR and PD-1 levels, undermining its role as the AhR-PD-1 axis modulator. These results provide new insights into the impact of exercise on AhR-signaling, which could potentially be relevant for various chronic diseases.