Effects of increased nitrate intake from beetroot juice on blood markers of oxidative stress and inflammation in older adults with hypertension.

BACKGROUND: Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans. AIM: In this randomised, placebo-controlled crossover study, by measuring a combination of multiple blood biomarkers, we evaluated whether previously reported benefits of dietary nitrate translate to a reduced oxidative stress and an improved inflammation status in 15 men and women (age range: 56-71 years) with treated hypertension. METHODS: We investigated the effects of a single ∼400 mg-dose of nitrate at 3 h post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate over 4 weeks (4WK POST), through nitrate-rich versus nitrate-depleted (placebo) beetroot juice. Measurements included plasma nitrate and nitrite (NOx), oxidised low-density lipoprotein (oxLDL), F2-isoprostanes, protein carbonyls, oxidised (GSSG) and reduced glutathione (GSH); and serum high-sensitive C-reactive protein (hsCRP), chemokines, cytokines, and adhesion molecules. Flow cytometry was used to assess the relative proportion of blood monocyte subsets. RESULTS: At 4WK POST nitrate intervention, the oxLDL/NOx ratio decreased (mainly due to increases in plasma nitrate and nitrite) and the GSH/GSSG ratio (a sensitive biomarker for alterations in the redox status) increased, compared with placebo (for both ratios P < 0.01). The relative proportion of classical (CD14+CD16-) monocytes decreased at 4WK POST for placebo compared to nitrate intervention (P < 0.05). Other oxidative stress and inflammatory markers were not altered by increased nitrate intake relative to placebo. CONCLUSIONS: The data from this study point toward a subtle alteration in the redox balance toward a less pro-oxidative profile by a regular intake of inorganic nitrate from plant foods. CLINICAL TRIAL REGISTRY NUMBER: NCT04584372 (ClinicialTrials.gov).

Menstrual cycle tracking in professional volleyball athletes.

Introduction: The menstrual cycle may affect well-being and physical performance of elite female athletes by interfering with the function of multiple physiological systems. The aim of this study was to characterize the symptoms of the menstrual cycle and their frequency in elite female volleyball players. Methods: Twenty professional female volleyball players were instructed to track their menstrual symptoms over the course of the first German national league season using the FitrWoman® tracking app. The app recorded the cycle length, duration, and intensity of the period as well as the occurrence and frequency of frequent cycle symptoms. The reported symptoms were then categorized into four categories (frequently, sometimes, rare, never) in order to create an individual Menstrual Symptom index (MSi) for each athlete. Results: The most frequently occurring symptoms among all players without hormonal contraception (non-HC; n = 15) were "stomach cramps" (n = 15), "sleep disturbances" (n = 11), and "tiredness" (n = 11). The average number of symptoms counted per cycle was 11.8 (±17.7) and the average calculated MSi within the team was 12.9 (±10.7) points for non-HC users. The HC players (n = 4) also regularly experienced symptoms such as "sleep disturbances" or "tendered breasts". The most common symptoms "stomach cramps" and "disturbed sleep" occurred more frequently during menstruation, while symptoms such as "bloating", "cravings" or "tendered breasts" did also peak before menstruation. Discussion: Menstrual cycle symptoms can be highly individual within a professional sports team. The calculation of the MSi seems to be a simple and accessible method to describe and overview the intensity and prevalence of symptoms in top female athletes in sports games.

Exercise-induced inflammation alters the perception and visual exploration of emotional interactions.

Introduction: The study aimed to investigate whether an exercise-induced pro-inflammatory response alters the perception as well as visual exploration of emotional body language in social interactions. Methods: In a within-subject design, 19 male, healthy adults aged between 19 and 33 years performed a downhill run for 45 min at 70% of their VO2max on a treadmill to induce maximal myokine blood elevations, leading to a pro-inflammatory status. Two control conditions were selected: a control run with no decline and a rest condition without physical exercise. Blood samples were taken before (T0), directly after (T1), 3 h after (T3), and 24 h after (T24) each exercise for analyzing the inflammatory response. 3 h after exercise, participants observed point-light displays (PLDs) of human interactions portraying four emotions (happiness, affection, sadness, and anger). Participants categorized the emotional content, assessed the emotional intensity of the stimuli, and indicated their confidence in their ratings. Eye movements during the entire paradigm and self-reported current mood were also recorded. Results: The downhill exercise condition resulted in significant elevations of measured cytokines (IL6, CRP, MCP-1) and markers for muscle damage (Myoglobin) compared to the control running condition, indicating a pro-inflammatory state after the downhill run. Emotion recognition rates decreased significantly after the downhill run, whereas no such effect was observed after control running. Participants' sensitivity to emotion-specific cues also declined. However, the downhill run had no effect on the perceived emotional intensity or the subjective confidence in the given ratings. Visual scanning behavior was affected after the downhill run, with participants fixating more on sad stimuli, in contrast to the control conditions, where participants exhibited more fixations while observing happy stimuli. Conclusion: Our study demonstrates that inflammation, induced through a downhill running model, impairs perception and emotional recognition abilities. Specifically, inflammation leads to decreased recognition rates of emotional content of social interactions, attributable to diminished discrimination capabilities across all emotional categories. Additionally, we observed alterations in visual exploration behavior. This confirms that inflammation significantly affects an individual's responsiveness to social and affective stimuli.

Respiratory and Metabolic Responses of CD4 + T Cells to Acute Exercise and their Association with Cardiorespiratory Fitness.

INTRODUCTION: The study aimed to investigate to what extent acute endurance exercise, especially eccentric exercise and cardiorespiratory fitness affect the metabolic profile of CD4 + cells. METHODS: 15 male, healthy adults aged between 20 and 33 years with a maximal oxygen uptake (VO 2max ) between 44 and 63 ml/kg/min performed a downhill run (DR) and a level run (LR) for 45 minutes at 70% of their VO 2max on a treadmill in a cross-over design. Blood samples were taken before (T0), directly after (T1), 3 hours after (T3), and 24 hours (T24) after each exercise for analyzing leukocyte numbers and cytokine levels. Isolated CD4 + cells were incubated for 4 hours in autologous resting versus 3 hours after exercise serum (T3 DR and T3 LR), and subsequently, cellular respiration, transcriptomic, and metabolomics profiles were measured. RESULTS: The systemic immune inflammation index increased significantly after DR and LR at T1 and T3 (p < .001). In contrast, the transcriptomic and metabolic profile of CD4 + cells showed no significant alterations after incubation in T3 exercise serum. However, cardiorespiratory fitness positively correlated with the maximal mitochondrial respiration in CD4 + cells after incubation with T3 LR serum (r = .617, p = .033) and with gene expression of oxidative phosphorylation and levels of different metabolites. Similarly, VO 2max was associated with an anti-inflammatory profile on RNA level. Lower lactate, methylmalonic acid, and D-gluconic acid levels were found in CD4 + cells of participants with a high VO 2max (p < .001). CONCLUSIONS: Acute exercise leads to a mild pro-inflammatory milieu with only small changes in the metabolic homeostasis of CD4 + cells. High cardiorespiratory fitness is associated with a metabolic shift to oxidative phosphorylation in CD4 + cells. Functional relevance of this metabolic shift needs to be further investigated.

The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

Association of cardiorespiratory fitness level with vascular function and subclinical atherosclerosis in the elderly.

PURPOSE: Physical exercise is crucial for healthy aging and plays a decisive role in the prevention of atherosclerotic cardiovascular disease (ASCVD). A higher level of cardiorespiratory fitness (CRF) in the elderly is associated with lower cardiovascular and all-cause mortality. This study investigated the association of CRF level with vascular function and cardiovascular risk factors in the elderly. METHODS: We examined 79 apparently healthy and physically active subjects aged > 55 years (64 ± 4 years). Cardiovascular functional parameters assessed included brachial and central blood pressure (BP), pulse wave velocity (PWV), augmentation index (Aix), and ankle-brachial index. Sonography of the common carotid artery was performed. CRF level was determined by a cardiopulmonary exercise test, and everyday activity was quantified with an accelerometer. RESULTS: All participants had a higher CRF level than the reported age-specific normative values. Twenty-nine subjects had subclinical atherosclerosis of the common carotid artery. Compared with participants without atherosclerosis, they were older (p = 0.007), displayed higher brachial systolic BP (p = 0.006), and higher central systolic BP (p = 0.014). Lower brachial (p = 0.036) and central (p = 0.003) systolic BP, lower PWV (p = 0.004), lower Aix (p < 0.001), lower body fat percentage (< 0.001), and lower LDL cholesterol (p = 0.005) were associated with a higher CRF level. CONCLUSIONS: In this cohort of healthy and physically active individuals, subjects with subclinical atherosclerosis displayed higher systolic brachial and central BP. A higher CRF level was associated with enhanced vascular function, consistent with an influence of CRF on both BP and vascular function in the elderly.

Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study.

OBJECTIVE: To investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men. METHODS: Eighteen individuals were classified as normal weight (NW; n = 9 - age: 25 ± 5 and BMI: 21.4 ± 1.7) and overweight/obese (OW; n = 9 - age: 29 ± 7 and BMI: 29.2 ± 2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-ß1 and ß2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Individuals with overweight/obese (OW) presented higher glucose (P = 0.009) and leptin (P = 0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P = 0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P = 0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-ß2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P = 0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3+CD4+ T cells (P = 0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8+ T cells (P = 0.001) than NW. CONCLUSION: Central obesity promoted reductions in interleukin 10 production response and increase in AR-ß2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults.

Optimizing the Gut Microbiota for Individualized Performance Development in Elite Athletes.

The human gut microbiota can be compared to a fingerprint due to its uniqueness, hosting trillions of living organisms. Taking a sport-centric perspective, the gut microbiota might represent a physiological system that relates to health aspects as well as individualized performance in athletes. The athletes' physiology has adapted to their exceptional lifestyle over the years, including the diversity and taxonomy of the microbiota. The gut microbiota is influenced by several physiological parameters and requires a highly individual and complex approach to unravel the linkage between performance and the microbial community. This approach has been taken in this review, highlighting the functions that the microbial community performs in sports, naming gut-centered targets, and aiming for both a healthy and sustainable athlete and performance development. With this article, we try to consider whether initiating a microbiota analysis is practicable and could add value in elite sport, and what possibilities it holds when influenced through a variety of interventions. The aim is to support enabling a well-rounded and sustainable athlete and establish a new methodology in elite sport.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques, levels of LDL, and cardiorespiratory fitness in the elderly.

BACKGROUND: Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (Tregs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures. METHODS: A cross-sectional study was performed in 79 participants (male: n = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of Tregs and their subtypes (resting (rTregs) and effector/memory (mTregs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters. RESULTS: SAP was detected in a total of 29 participants. The participants with plaque were older (64.5 ± 3.6 years vs. 62.9 ± 3.5 years) and had higher peripheral systolic blood pressure (133.8 ± 14.7 mmHg vs. 125.8 ± 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rTregs (28.8% ± 10.7% vs. 34.6% ± 10.7%) and a higher percentage of mTregs (40.3% ± 14.7% vs. 30.0% ± 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01-1.42)) and mTregs (OR = 1.05 (95%CI: 1.02-1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake (ß = 0.441), low-density lipoprotein (LDL) (ß = -0.096), and SAP (ß = 6.733) with mTregs and LDL (ß = 0.104) with rTregs. CONCLUSION: While at an early stage of SAP, the total proportion of Tregs gives no indication of vascular changes, this is indicated by a shift in the Treg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle-based preventive measures at an early stage, which may have a protective effect against disease progression.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

T-cell-derived TNF-α and a cluster of immunological parameters from plasma allow a separation between SARS-CoV-2 convalescent versus vaccinated elite athletes.

Guidelines for medical clearing after SARS-CoV-2 infection in elite athletes do not include T-cell immunity aspects despite its relevance in the course of COVID-19 disease. Therefore, we aimed to analyze T-cell-related cytokines before and after in-vitro activation of CD4+ T-cells. We sampled professional indoor sports athletes at medical clearing after SARS-CoV-2 infection obtaining clinical, fitness data, and serological data including CD4+ T-cell cytokines. All data were analyzed by principal component analysis and 2 × 2 repeated measures ANOVA. CD4+ T-cells were sampled for cell culture activation with anti-CD3/anti-CD28 tetramers. At medical clearing, CD4+ T-cells from convalescent athletes secreted increased levels of TNF-α 72 h after in-vitro activation compared to vaccinated athletes. IL-18 levels in plasma were elevated and a cluster of parameters differentiated convalescent from vaccinated athletes by 13 parameters at the timepoint of medical clearing. All clinical data indicate infection is resolved, while increased TNF-α may reflect altered proportions of peripheral T-cells as a hangover of infection.

Effect of supplementation of vitamin D3 or vitamin D2 on serum concentrations of free and total 25-hydroxyvitamin D and the expression of genes involved in immune function in peripheral blood mononuclear cells of weaned pigs.

The present study aimed to compare the effects of vitamin D2 and vitamin D3 supplementation on concentrations of total and free 25(OH)D in plasma and the expression of genes involved in the innate immune system in peripheral blood mononuclear cells (PBMC) in weaned pigs. Five groups of pigs (with an initial body weight of around 9 kg) received basal diets supplemented with either 500 (control group), 1000 or 2000 IU vitamin D3/kg diet or 1000 or 2000 IU vitamin D2/kg diet for a period of 4 weeks. Vitamin D supplementation did not influence feed intake, body weight gain, feed conversion ratio, apparent total tract digestibility of calcium and phosphorus, and serum concentrations of calcium, inorganic phosphate and parathyroid hormone. Supplementation of vitamin D3 led to a dose-dependent increase of the concentrations of total and free 25(OH)D in serum. In contrast, pigs supplemented with 1000 or 2000 IU vitamin D2/kg diet did not have higher concentrations of total and free 25(OH)D in serum than the control group. The ratio of free/total 25(OH)D in serum was not influenced by vitamin D3 supplementation, whereas the group supplemented with 2000 IU vitamin D2/kg diet had a higher free/total 25(OH)D ratio than the groups supplemented with 1000 or 2000 IU vitamin D3/kg diet. Genes involved in vitamin D signalling (CYP27B1, VDR), as well as pro-inflammatory and immune regulatory genes (TLR4, TNF, IL1B and TGFB1) and genes encoding porcine protegrins (NPG1, NPG4), proteins belonging to the group of antimicrobial peptides, in PBMC were not different among groups supplemented with vitamin D3 or vitamin D2 and the control group. Therefore, the study indicates that supplementation of vitamin D2 causes much lower levels of total 25(OH)D than supplementation of vitamin D3 and that supplementation of vitamins D2 or D3 at moderate levels does not have an impact on the innate immune function in healthy pigs.

Blood-Based Biomarkers for Managing Workload in Athletes: Perspectives for Research on Emerging Biomarkers.

At present, various blood-based biomarkers have found their applications in the field of sports medicine. This current opinion addresses biomarkers that warrant consideration in future research for monitoring the athlete training load. In this regard, we identified a variety of emerging load-sensitive biomarkers, e.g., cytokines (such as IL-6), chaperones (such as heat shock proteins) or enzymes (such as myeloperoxidase) that could improve future athlete load monitoring as they have shown meaningful increases in acute and chronic exercise settings. In some cases, they have even been linked to training status or performance characteristics. However, many of these markers have not been extensively studied and the cost and effort of measuring these parameters are still high, making them inconvenient for practitioners so far. We therefore outline strategies to improve knowledge of acute and chronic biomarker responses, including ideas for standardized study settings. In addition, we emphasize the need for methodological advances such as the development of minimally invasive point-of-care devices as well as statistical aspects related to the evaluation of these monitoring tools to make biomarkers suitable for regular load monitoring.

Blood-Based Biomarkers for Managing Workload in Athletes: Considerations and Recommendations for Evidence-Based Use of Established Biomarkers.

Blood-based biomarkers can provide an objective individualized measure of training load, recovery, and health status in order to reduce injury risk and maximize performance. Despite enormous potentials, especially owing to currently evolving technology, such as point-of-care testing, and advantages, in terms of objectivity and non-interference with the training process, there are several pitfalls in the use and interpretation of biomarkers. Confounding variables such as preanalytical conditions, inter-individual differences, or an individual chronic workload can lead to variance in resting levels. In addition, statistical considerations such as the detection of meaningful minimal changes are often neglected. The lack of generally applicable and individual reference levels further complicates the interpretation of level changes and thus load management via biomarkers. Here, the potentials and pitfalls of blood-based biomarkers are described, followed by an overview of established biomarkers currently used to support workload management. Creatine kinase is discussed in terms of its evidence for workload management to illustrate the limited applicability of established markers for workload management to date. We conclude with recommendations for best practices in the use and interpretation of biomarkers in a sport-specific context.

12-week combined strength and endurance exercise attenuates CD8+ T-cell differentiation and affects the kynurenine pathway in the elderly: a randomized controlled trial.

BACKGROUND: Age-related accumulation of highly differentiated CD8+ effector memory re-expressing CD45RA (EMRA) T-cells and disruption of the kynurenine (KYN) pathway are associated with chronic inflammation and the development of insulin resistance. In this study the aim was to investigate the effects of 12-week combined strength and endurance exercise on CD8+ T-cell differentiation and KYN pathway metabolites. Ninety-six elderly subjects (f/m, aged 50-70) were randomized to a control (CON) or exercise (EX) group. The EX group completed combined strength and endurance training twice weekly for one hour each time at an intensity of 60% of the one-repetition maximum for strength exercises and a perceived exertion of 15/20 for endurance exercises. The EX group was also randomly subdivided into two groups with or without a concomitant balanced diet intervention in order to examine additional effects besides exercise alone. Before and after the intervention phase, the proportions of CD8+ T-cell subsets and levels of KYN pathway metabolites in peripheral blood were determined. RESULTS: The CD8+ EMRA T-cell subsets increased in the CON group but remained almost unchanged in the EX group (p = .02). Plasma levels of kynurenic acid (KA) increased in the EX group and decreased in the CON group (p = .03). Concomitant nutritional intervention resulted in lower levels of quinolinic acid (QA) compared with exercise alone (p = .03). Overall, there was a slight increase in the QA/KA ratio in the CON group, whereas it decreased in the EX group (p > .05). CONCLUSIONS: Combined strength and endurance training seems to be a suitable approach to attenuate CD8+ T-cell differentiation in the elderly and to redirect the KYN pathway towards KA. The clinical relevance of these effects needs further investigation.

Autophagy of naïve CD4+ T cells in aging - the role of body adiposity and physical fitness.

Life expectancy has increased exponentially in the last century accompanied by disability, poor quality of life, and all-cause mortality in older age due to the high prevalence of obesity and physical inactivity in older people. Biologically, the aging process reduces the cell's metabolic and functional efficiency, and disrupts the cell's anabolic and catabolic homeostasis, predisposing older people to many dysfunctional conditions such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. In the immune system, aging also alters cells' metabolic and functional efficiency, a process known as 'immunosenescence', where cells become more broadly inflammatory and their functionality is altered. Notably, autophagy, the conserved and important cellular process that maintains the cell's efficiency and functional homeostasis may protect the immune system from age-associated dysfunctional changes by regulating cell death in activated CD4+ T cells. This regulatory process increases the delivery of the dysfunctional cytoplasmic material to lysosomal degradation while increasing cytokine production, proliferation, and differentiation of CD4+ T cell-mediated immune responses. Poor proliferation and diminished responsiveness to cytokines appear to be ubiquitous features of aged T cells and may explain the delayed peak in T cell expansion and cytotoxic activity commonly observed in the 'immunosenescence' phenotype in the elderly. On the other hand, physical exercise stimulates the expression of crucial nutrient sensors and inhibits the mechanistic target of the rapamycin (mTOR) signaling cascade which increases autophagic activity in cells. Therefore, in this perspective review, we will first contextualize the overall view of the autophagy process and then, we will discuss how body adiposity and physical fitness may counteract autophagy in naïve CD4+ T cells in aging.

An International Multidisciplinary Delphi-Based Consensus on Heat Therapy in Musculoskeletal Pain.

INTRODUCTION: Musculoskeletal pain (MP) is prevalent in our society, having a strong negative impact on physical and psychosocial quality of life. Heat therapy (HT) has been frequently described as a treatment strategy for musculoskeletal pain, but scientific evidence is still poor. The aim of the present Delphi method study is to gather a consensus among European experts on the role of HT in MP. METHODS: To address this topic, a list of 54 statements was developed, concerning mechanism of action of heat on muscle, types of MP eligible for heat treatment, efficacy of HT, time and modalities of treatment, maximizing compliance to HT, safety (based on heat wraps), wrong beliefs and common errors in the prescription of HT and the role of HT in preventing muscular damage in athletes. The survey was distributed to 116 European experts, using a 5-point Likert scale to express agreement or disagreement with the statements; 66% concordance with the statements was needed to define a consensus. RESULTS: Consensus was reached on 78% of statements. There was a strong consensus on the mechanism of action of heat on muscle, the indication in chronic MP, its effectiveness as part of a multimodal approach to MP and the safety and tolerability of superficial heat therapy. A low-level of consensus was obtained on the role of heat in preventing muscular damage and in acute MP. CONCLUSION: This Delphi consensus recognizes the role of HT mostly in chronic MP and highlights the need for stronger scientific evidence to regulate the use of this therapy in clinical practice.