A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy.

PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.

Interindividual variation in maximum aerobic metabolism varies with gill morphology and myocardial bioenergetics in Gulf killifish.

This study asked whether interindividual variation in maximum and standard aerobic metabolic rates of the Gulf killifish, Fundulus grandis, correlates with gill morphology and cardiac mitochondrial bioenergetics, traits reflecting critical steps in the O2 transport cascade from the environment to the tissues. Maximum metabolic rate (MMR) was positively related to body mass, total gill filament length and myocardial oxygen consumption during maximum oxidative phosphorylation (multiple R2=0.836). Standard metabolic rate (SMR) was positively related to body mass, total gill filament length and myocardial oxygen consumption during maximum electron transport system activity (multiple R2=0.717). After controlling for body mass, individuals with longer gill filaments, summed over all gill arches, or greater cardiac respiratory capacity had higher whole-animal metabolic rates. The overall model fit and the explanatory power of individual predictor variables were better for MMR than for SMR, suggesting that gill morphology and myocardial bioenergetics are more important in determining active rather than resting metabolism. After accounting for body mass, heart ventricle mass was not related to variation in MMR or SMR, indicating that the quality of the heart (i.e. the capacity for mitochondrial metabolism) was more influential than heart size. Finally, the myocardial oxygen consumption required to offset the dissipation of the transmembrane proton gradient in the absence of ATP synthesis was not correlated with either MMR or SMR. The results support the idea that interindividual variation in aerobic metabolism, particularly MMR, is associated with variation in specific steps in the O2 transport cascade.

Supplemental Watermelon Juice Attenuates Acute Hyperglycemia-Induced Macro-and Microvascular Dysfunction in Healthy Adults.

BACKGROUND: Acute hyperglycemia reduces NO bioavailability and causes macro- and microvascular dysfunction. Watermelon juice (WMJ) is a natural source of the amino acid citrulline, which is metabolized to form arginine for the NO cycle and may improve vascular function. OBJECTIVES: We examined the effects of 2 weeks of WMJ compared to a calorie-matched placebo (PLA) to attenuate acute hyperglycemia-induced vascular dysfunction. METHODS: In a randomized, placebo-controlled, double-blind, crossover trial, 6 men and 11 women (aged 21-25; BMI, 23.5 ± 3.2 kg/m2) received 2 weeks of daily WMJ (500 mL) or a PLA drink followed by an oral-glucose-tolerance test. Postprandial flow-mediated dilation (FMD) was measured by ultrasound (primary outcome), while postprandial microvascular blood flow (MVBF) and ischemic reperfusion were measured by near-infrared spectroscopy (NIRS) vascular occlusion test (VOT). RESULTS: The postprandial FMD area AUC was higher after WMJ supplementation compared to PLA supplementation (838 ± 459% · 90 min compared with 539 ± 278% · 90 min; P = 0.03). The postprandial MVBF (AUC) was higher (P = 0.01) following WMJ supplementation (51.0 ± 29.1 mL blood · 100 mL tissue-1 · min-1 · 90 min) compared to the PLA (36.0 ± 20.5 mL blood · 100 mL tissue-1 · min-1 · 90 min; P = 0.01). There was a significant treatment effect (P = 0.048) for WMJ supplementation (71.2 ± 1.5%) to increase baseline tissue oxygen saturation (StO2%) when compared to PLA (65.9 ± 1.7%). The ischemic-reperfusion slope was not affected by WMJ treatment (P = 0.83). CONCLUSIONS: Two weeks of daily WMJ supplementation improved FMD and some aspects of microvascular function (NIRS-VOT) during experimentally induced acute hyperglycemia in healthy adults. Preserved postprandial endothelial function and enhanced skeletal muscle StO2% are likely partially mediated by increased NO production (via citrulline conversion into arginine) and by the potential antioxidant effect of other bioactive compounds in WMJ.

The Panacea of Human Aging: Calorie Restriction Versus Exercise.

Primary aging is the progressive decline in health and fitness and depends on metabolic rate and oxidative stress. Untoward changes in body composition and metabolic function characterize secondary aging. We hypothesize that both exercise and calorie restriction (CR) improve secondary aging, but only CR improves primary. However, CR followed with exercise is a superior strategy to maintain overall health and quality of life with age.

Precision exercise medicine: understanding exercise response variability.

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.

Application of high-resolution mass spectrometry to measure low abundance isotope enrichment in individual muscle proteins.

Stable isotope-labeled amino acids have long been used to measure the fractional synthesis rate of proteins, although the mass spectrometry platforms used for such analyses have changed throughout the years. More recently, tandem mass spectrometers such as triple quadrupoles have been accepted as the standard platform for enrichment measurement due to their sensitivity and the enhanced specificity offered by multiple reaction monitoring (MRM) experiments. The limit in the utility of such platforms for enrichment analysis occurs when measuring very low levels of enrichment from small amounts of sample, particularly proteins isolated from two-dimensional gel electrophoresis (2D-GE), where interference from contaminant ions impacts the sensitivity of the measurement. We therefore applied a high-resolution orbitrap mass spectrometer to the analysis of [ring-(13)C6]-phenylalanine enrichment in individual muscle proteins isolated with 2D-GE. Comparison of samples analyzed on both platforms revealed that the high-resolution MS has significantly improved sensitivity relative to the triple quadrupole MS at very low-level enrichments due to its ability to resolve interferences in the m/z dimension. At higher enrichment levels, enrichment measurements from the orbitrap platform showed significant correlation (R (2) > 0.5) with those of the triple quadrupole platform. Together, these results indicate that high-resolution MS platforms such as the orbitrap are not only as capable of performing isotope enrichment measurements as the more commonly preferred triple quadrupole instruments, but offer unparalleled advantages in terms of mass accuracy and sensitivity in the presence of similar-mass contaminants.

A single exposure to 100% normo-baric oxygen therapy appears to improve sequence learning processes by increasing prefrontal cortex oxygen saturation.

Previously, we showed that a normo-baric 100 % oxygen treatment (NbOxTr) enhances motor learning processes, e.g., visuomotor adaptation (VMA) and sequence learning (SL). However, this work was limited to behavioral outcomes and did not identify the physiological mechanistic underpinnings of these improvements. Here, we expand on this research to investigate the effects of a NbOxTr on the oxygen tissue saturation index (TSI) level of the prefrontal cortex (PFC) when performing a SL task and whether potential SL improvements relate to increased TSI levels in the PFC. Twenty four right-handed young, healthy adults were randomly assigned to a NbOxTr group (normo-baric 100 % oxygen, n = 12) or a control group (normal air, n = 12). They received their respective treatments via a nasal cannula during the experiment. Oxygen TSI levels of the right and left PFC were measured via near-infrared spectroscopy (NIRS) throughout different SL task phases (Baseline, Training, Testing). The NbOxTr increased the TSI of the PFC in the Training phase (p < 0.01) and positively affected SL retention in the Testing phase (p < 0.05). We also found a positive correlation between TSI changes in the right PFC during the gas treatment phase (3.4 % increase) and response time (RT) improvements in the SL task training and retention phase (all p < 0.05). Our results suggest that a simple NbOxTr increases the oxygenated hemoglobin availability in the PFC, which appears to mediate the retention of acquired SL improvements in healthy young adults. Future studies should examine treatment-related oxygenation changes in other brain areas involved and their relation to enhanced learning processes. Whether this NbOxTr improves SL in neurologically impaired populations should also be examined.

Impact of low-load resistance exercise with and without blood flow restriction on muscle strength, endurance, and oxidative capacity: A pilot study.

Low-load resistance exercise (LLRE) to failure can increase muscle mass, strength, endurance, and mitochondrial oxidative capacity (OXPHOS). However, the impact of adding blood flow restriction to low-load resistance exercise (LLBFR) when matched for volume on these outcomes is incompletely understood. This pilot study examined the impact of 6 weeks of single-legged LLBFR and volume-matched LLRE on thigh bone-free lean mass, strength, endurance, and mitochondrial OXPHOS. Twenty (12 males and 8 females) untrained young adults (mean ± SD; 21 ± 2 years, 168 ± 11 cm, 68 ± 12 kg) completed 6 weeks of either single-legged LLBFR or volume-matched LLRE. Participants performed four sets of 30, 15, 15, and 15 repetitions at 25% 1-RM of leg press and knee extension with or without BFR three times per week. LLBFR increased knee extension 1-RM, knee extension endurance, and thigh bone-free lean mass relative to control (all p < 0.05). LLRE increased leg press and knee extension 1-RM relative to control (p = 0.012 and p = 0.054, respectively). LLRE also increased mitochondrial OXPHOS (p = 0.047 (nonparametric)). Our study showed that LLBFR increased muscle strength, muscle endurance, and thigh bone-free lean mass in the absence of improvements in mitochondrial OXPHOS. LLRE improved muscle strength and mitochondrial OXPHOS in the absence of improvements in thigh bone-free lean mass or muscle endurance.

Blood and MRI biomarkers of mild traumatic brain injury in non-concussed collegiate football players.

Football has one of the highest incidence rates of mild traumatic brain injury (mTBI) among contact sports; however, the effects of repeated sub-concussive head impacts on brain structure and function remain under-studied. We assessed the association between biomarkers of mTBI and structural and functional MRI scans over an entire season among non-concussed NCAA Division I linemen and non-linemen. Concentrations of S100B, GFAP, BDNF, NFL, and NSE were assessed in 48 collegiate football players (32 linemen; 16 non-linemen) before the start of pre-season training (pre-camp), at the end of pre-season training (pre-season), and at the end of the competitive season (post-season). Changes in brain structure and function were assessed in a sub-sample of 11 linemen and 6 non-linemen using structural and functional MRI during the execution of Stroop and attention network tasks. S100B, GFAP and BDNF concentrations were increased at post-season compared to pre-camp in linemen. White matter hyperintensities increased in linemen during pre-season camp training compared to pre-camp. This study showed that the effects of repeated head impacts are detectable in the blood of elite level non-concussed collegiate football players exposed to low-moderate impacts to the heads, which correlated with some neurological outcomes without translating to clinically-relevant changes in brain anatomy or function.

Boost your brain: a simple 100% normobaric oxygen treatment improves human motor learning processes.

Introduction: Human motor learning processes are a fundamental part of our daily lives and can be adversely affected by neurologic conditions. Motor learning largely depends on successfully integrating cognitive and motor-related sensory information, and a simple, easily accessible treatment that could enhance such processes would be exciting and clinically impactful. Normobaric 100% oxygen treatment (NbOxTr) is often used as a first-line intervention to improve survival rates of brain cells in neurological trauma, and recent work indicates that improvements in elements crucial for cognitive-motor-related functions can occur during NbOxTr. However, whether NbOxTr can enhance the motor learning processes of healthy human brains is unknown. Here, we investigated whether a brief NbOxTr administered via nasal cannula improves motor learning processes during a visuomotor adaptation task where participants adapt to a visual distortion between visual feedback and hand movements. Methods: 40 healthy young adults (M = 21 years) were randomly assigned to a NbOxTr (N = 20; 100% oxygen) or air (N = 20; regular air) group and went through four typical visuomotor adaptation phases (Baseline, Adaptation, After-Effect, Refresher). Gas treatment (flow rate 5 L/min) was only administered during the Adaptation phase of the visuomotor experiment, in both groups. Results: The NbOxTr provided during the Adaptation phase led to significantly faster and about 30% improved learning (p < 0.05). Notably, these motor learning improvements consolidated into the subsequent experiment phases, i.e., after the gas treatment was terminated (p < 0.05). Discussion: We conclude that this simple and brief NbOxTr dramatically improved fundamental human motor learning processes and may provide promising potential for neurorehabilitation and skill-learning approaches. Further studies should investigate whether similar improvements exist in elderly and neurologically impaired individuals, other motor learning tasks, and also long-lasting effects.

A simple 100% normobaric oxygen treatment can substantially enhance sequence learning processes.

Motor learning processes are crucial for our everyday life, and improving skills by tailored interventions is of great clinical interest and value. Our previous work revealed a positive effect of normo-baric oxygen treatment on visuomotor adaptation. Here, we investigate whether it could positively affect sequence learning (SL) processes as well. Sixty-four healthy young adults were divided into a 100% oxygen treatment (NbOxTr; N = 32, M=20.7 ± 1.63 yrs.) and a normal air treatment (AirTr; N = 32, M=20.8 ± 0.95 yrs.) group. Participants performed a standardized SL task by pressing the spatial-compatible key on a keyboard according to four visual stimuli with two pre-determined 8-item sequences with different training depths. Following a baseline session (10 trials), both groups received a gas treatment (5 L/min, via nasal cannula) during the next training session (4 blocks, 45 trials each block), followed by a testing session (30 trials) without gas treatment. On day two, participants completed another 30 trials, similar to the first-day testing session, also without gas treatment. ANOVA revealed no significant group differences during baseline (p > 0.05) but a significantly faster response time (+45.5%) in the NbOxTr than AirTr group in the training session with gas treatment for all training depths (p < 0.05). The positive NbOxTr effect consolidated into the following testing session without gas treatment for deeply trained sequences (+17%; p < 0.05), and for all training depth on day-two testing (+45.2%; p < 0.05). Results suggest that the NbOxTr substantially improved participants' SL processing speed. Notably, improvements consolidated after an overnight sleep. The present work confirms a beneficial effect of a single, simple NbOxTr on fundamental motor learning processes. This treatment approach may provide promising implications for practice in neurological rehabilitation and other motor learning-related scenarios and should be further investigated in future research.

The Effect of Watermelon Juice Supplementation on Heart Rate Variability and Metabolic Response during an Oral Glucose Challenge: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial.

Heart rate variability (HRV) provides a simple method to evaluate autonomic function in health and disease. A reduction in HRV may indicate autonomic dysfunction and is strongly associated with aspects of cardiometabolic disease, including hyperglycemia. Reduced nitric oxide (NO) bioavailability is also implicated in the development of cardiometabolic disease and autonomic dysfunction. Watermelons are natural sources of L-arginine and L-citrulline, substrates used for NO synthesis. Watermelon consumption can improve NO bioavailability. We conducted a randomized, double-blind, placebo-controlled crossover trial to test the effects of 2 weeks of daily watermelon juice (WMJ) supplementation on HRV in response to an oral glucose challenge (OGC) in healthy young adults. We also performed indirect calorimetry to assess if our intervention altered the metabolic response to the OGC. WMJ supplementation preserved high-frequency power (HF) (treatment effect, p = 0.03) and the percentage of successive differences that differ by more than 50 ms (pNN50) (treatment effect, p = 0.009) when compared to the placebo treatment. There was no difference in resting energy expenditure or substate oxidation according to treatment. We report that WMJ supplementation attenuates OGC-induced reductions in HRV. Future work should emphasize the importance of NO bioavailability in autonomic dysfunction in cardiometabolic disease.

Smartphone prediction of skeletal muscle mass: model development and validation in adults.

BACKGROUND: Skeletal muscle is a large and clinically relevant body component that has been difficult and impractical to quantify outside of specialized facilities. Advances in smartphone technology now provide the opportunity to quantify multiple body surface dimensions such as circumferences, lengths, surface areas, and volumes. OBJECTIVES: This study aimed to test the hypothesis that anthropometric body measurements acquired with a smartphone application can be used to accurately estimate an adult's level of muscularity. METHODS: Appendicular lean mass (ALM) measured by DXA served as the reference for muscularity in a sample of 322 adults. Participants also had digital anthropometric dimensions (circumferences, lengths, and regional and total body surface areas and volumes) quantified with a 20-camera 3D imaging system. Least absolute shrinkage and selection operator (LASSO) regression procedures were used to develop the ALM prediction equations in a portion of the sample, and these models were tested in the remainder of the sample. Then, the accuracy of the prediction models was cross-validated in a second independent sample of 53 adults who underwent ALM estimation by DXA and the same digital anthropometric estimates acquired with a smartphone application. RESULTS: LASSO models included multiple significant demographic and 3D digital anthropometric predictor variables. Evaluation of the models in the testing sample indicated respective RMSEs in women and men of 1.56 kg and 1.53 kg and R2's of 0.74 and 0.90, respectively. Cross-validation of the LASSO models in the smartphone application group yielded RMSEs in women and men of 1.78 kg and 1.50 kg and R2's of 0.79 and 0.95; no significant differences or bias between measured and predicted ALM values were observed. CONCLUSIONS: Smartphone image capture capabilities combined with device software applications can now provide accurate renditions of the adult muscularity phenotype outside of specialized laboratory facilities. Am J Clin Nutr 2023;x:xx. This trial was registered at clinicaltrials.gov as NCT03637855 (https://clinicaltrials.gov/ct2/show/NCT03637855), NCT05217524 (https://clinicaltrials.gov/ct2/show/NCT05217524), and NCT03771417 (https://clinicaltrials.gov/ct2/show/NCT03771417).

Acute Exercise Increases NK Cell Mitochondrial Respiration and Cytotoxicity against Triple-Negative Breast Cancer Cells under Hypoxic Conditions.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive, highly metastatic malignancy with high recurrence rates. Hypoxia is a hallmark of the TNBC tumor microenvironment, which promotes tumor growth while impairing natural killer (NK) cell cytotoxic functions. Although acute exercise improves NK cell function under normoxic conditions, the effect of exercise on NK cell cytotoxic functions under hypoxic conditions mimicking O 2 tensions observed in solid tumors is unknown. METHODS: The cytotoxic functions of resting and postexercise NK cells isolated from thirteen young inactive healthy women were assessed against breast cancer cells expressing different levels of hormone receptors (MCF-7 and MDA-MB-231) under normoxic and hypoxic conditions. Mitochondrial respiration and H 2 O 2 efflux rates of the TNBC-activated NK cells were assessed via high-resolution respirometry. RESULTS: Under hypoxia, postexercise NK cells exhibited greater killing of TNBC than resting NK cells. Further, postexercise NK cells were more likely to kill TNBC under hypoxia than normoxic conditions. In addition, mitochondrial respiration associated with oxidative (OXPHOS) capacity of TNBC-activated NK cells was greater in postexercise cells than resting cells under normoxia, but not under hypoxia. Finally, acute exercise was associated with reduced mitochondrial H 2 O 2 efflux by NK cells in both conditions. CONCLUSIONS: Together, we present crucial interrelationships between hypoxia and exercise-induced changes in NK cell functions against TNBC cells. By modulating their mitochondrial bioenergetic functions, we postulate that acute exercise improves NK cell function under hypoxic conditions. Specifically, NK cell O 2 and H 2 O 2 flow (pmol·s -1 ·million NK cells -1 ) changes in response to 30-min cycling suggest that exercise primes NK cell tumor killing by reducing mitochondrial oxidative stress and, thus, rescuing their function when exposed to harsh hypoxic environments as observed in the microenvironment of breast solid tumors.

Impact of maximal exercise on immune cell mobilization and bioenergetics.

Acute aerobic exercise increases the number and proportions of circulating peripheral blood mononuclear cells (PMBC) and can alter PBMC mitochondrial bioenergetics. In this study, we aimed to examine the impact of a maximal exercise bout on immune cell metabolism in collegiate swimmers. Eleven (7 M/4F) collegiate swimmers completed a maximal exercise test to measure anaerobic power and capacity. Pre- and postexercise PBMCs were isolated to measure the immune cell phenotypes and mitochondrial bioenergetics using flow cytometry and high-resolution respirometry. The maximal exercise bout increased circulating levels of PBMCs, particularly in central memory (KLRG1+/CD57-) and senescent (KLRG1+/CD57+) CD8+ T cells, whether measured as a % of PMBCs or as absolute concentrations (all p < 0.05). At the cellularlevel, the routine oxygen flow (IO2 [pmol·s-1 ·106 PBMCs-1 ]) increased following maximal exercise (p = 0.042); however, there were no effects of exercise on the IO2 measured under the LEAK, oxidative phosphorylation (OXPHOS), or electron transfer (ET) capacities. There were exercise-induced increases in the tissue-level oxygen flow (IO2-tissue [pmol·s-1 ·mL blood-1 ]) for all respiratory states (all p < 0.01), except for the LEAK state, after accounting for the mobilization of PBMCs. Future subtype-specific studies are needed to characterize further maximal exercise's true impact on immune cell bioenergetics.

Monitoring body composition change for intervention studies with advancing 3D optical imaging technology in comparison to dual-energy X-ray absorptiometry.

BACKGROUND: Recent 3-dimensional optical (3DO) imaging advancements have provided more accessible, affordable, and self-operating opportunities for assessing body composition. 3DO is accurate and precise in clinical measures made by DXA. However, the sensitivity for monitoring body composition change over time with 3DO body shape imaging is unknown. OBJECTIVES: This study aimed to evaluate the ability of 3DO in monitoring body composition changes across multiple intervention studies. METHODS: A retrospective analysis was performed using intervention studies on healthy adults that were complimentary to the cross-sectional study, Shape Up! Adults. Each participant received a DXA (Hologic Discovery/A system) and 3DO (Fit3D ProScanner) scan at the baseline and follow-up. 3DO meshes were digitally registered and reposed using Meshcapade to standardize the vertices and pose. Using an established statistical shape model, each 3DO mesh was transformed into principal components, which were used to predict whole-body and regional body composition values using published equations. Body composition changes (follow-up minus the baseline) were compared with those of DXA using a linear regression analysis. RESULTS: The analysis included 133 participants (45 females) in 6 studies. The mean (SD) length of follow-up was 13 (5) wk (range: 3-23 wk). Agreement between 3DO and DXA (R2) for changes in total FM, total FFM, and appendicular lean mass were 0.86, 0.73, and 0.70, with root mean squared errors (RMSEs) of 1.98 kg, 1.58 kg, and 0.37 kg, in females and 0.75, 0.75, and 0.52 with RMSEs of 2.31 kg, 1.77 kg, and 0.52 kg, in males, respectively. Further adjustment with demographic descriptors improved the 3DO change agreement to changes observed with DXA. CONCLUSIONS: Compared with DXA, 3DO was highly sensitive in detecting body shape changes over time. The 3DO method was sensitive enough to detect even small changes in body composition during intervention studies. The safety and accessibility of 3DO allows users to self-monitor on a frequent basis throughout interventions. This trial was registered at clinicaltrials.gov as NCT03637855 (Shape Up! Adults; https://clinicaltrials.gov/ct2/show/NCT03637855); NCT03394664 (Macronutrients and Body Fat Accumulation: A Mechanistic Feeding Study; https://clinicaltrials.gov/ct2/show/NCT03394664); NCT03771417 (Resistance Exercise and Low-Intensity Physical Activity Breaks in Sedentary Time to Improve Muscle and Cardiometabolic Health; https://clinicaltrials.gov/ct2/show/NCT03771417); NCT03393195 (Time Restricted Eating on Weight Loss; https://clinicaltrials.gov/ct2/show/NCT03393195), and NCT04120363 (Trial of Testosterone Undecanoate for Optimizing Performance During Military Operations; https://clinicaltrials.gov/ct2/show/NCT04120363).

Salivary immunity of elite collegiate American football players infected with SARS-CoV-2 normalizes following isolation.

The impact of COVID-19 on systemic immunity in the general population has been well characterized, however the short-term effects of COVID-19 infection on innate salivary immunity in elite-level athletes are unknown. Therefore, this study aimed to determine whether elite college football athletes had altered salivary immunity following the CDC-recommended isolation post-SARS-CoV-2 infection. Salivary samples were obtained from fourteen elite football players who tested positive for SARS-CoV-2 (n = 14), immediately after CDC-recommended isolation (average days = 14 ± 2 days) and fifteen controls who remained uninfected with SARS-CoV-2. Biomarkers of innate salivary immunity (sIgA and alpha-amylase), antimicrobial proteins (AMPs, i.e., HNP1-3, lactoferrin, LL-37) and lung inflammation (SPA, SPLI, and Neutrophil Elastase-alpha-1-antitrypsin complex) were measured. Independent student t-tests were used to determine changes in biomarkers between groups. Although all AMP levels were within normal range, Human Neutrophil Defensin 1-3 concentrations and secretion rates were higher in SARS-CoV-2+ compared to SARS-CoV-2-. This suggests that the CDC-recommended isolation period is sufficient to ensure that athletes' salivary immunity is not compromised upon return to sports, and athletes post-COVID-19 infection do not appear to be at greater risk for secondary infection than those with no history of COVID-19.

Impact of acute exercise on peripheral blood mononuclear cells nutrient sensing and mitochondrial oxidative capacity in healthy young adults.

Regular exercise is associated with changes in peripheral blood mononuclear cell (PBMC) proportions that have enhanced effector functions in young and old adults; however, the effects of acute exercise on PBMC nutrient sensors and metabolic function in active young adults is unknown. To fill this gap, activation status and nutrient-sensing mechanisms of PBMCs isolated from 21 healthy active adults (20-35 yr; 36.5 ± 6.3 V̇O2peak ) were characterized before and after 30 min of moderate-to-vigorous cycling (65%-75% V̇O2peak ). In addition, changes in PBMC mitochondrial respiratory function in response to exercise were assessed using high-resolution respirometry. There was an increase in the number of activated CD69+/CD4 (79% increase) and CD69+/CD8 (166% increase) T-cells in response to the acute bout of exercise, while the nutrient-sensing mechanisms remained unchanged. PBMC mitochondrial respiration did not increase on a cell-per-cell basis, however, mitochondrial oxidative capacity (OXPHOS) increased at the tissue level (18.6 pmol/(s*ml blood) versus 29.3 pmol/(s*ml blood); p < 0.05) in response to acute exercise. Thus, this study shows that acute exercise preferentially mobilizes activated T-cells while concomitantly increasing PBMC mitochondrial oxidative capacity at the tissue level, rather than acutely changing mitochondrial oxidative capacity at the cellular level in young adults.

Cytomegalovirus Infection Impairs the Mobilization of Tissue-Resident Innate Lymphoid Cells into the Peripheral Blood Compartment in Response to Acute Exercise.

Circulating immune cell numbers and phenotypes are impacted by high-intensity acute bouts of exercise and infection history with the latent herpesviruses cytomegalovirus (CMV). In particular, CMV infection history impairs the exercise-induced mobilization of cytotoxic innate lymphoid cells 1 (ILC1) cells, also known as NK cells, in the blood. However, it remains unknown whether exercise and CMV infection modulate the mobilization of traditionally tissue-resident non-cytotoxic ILCs into the peripheral blood compartment. To address this question, 22 healthy individuals with or without CMV (20-35 years-45% CMVpos) completed 30 min of cycling at 70% VO2 max, and detailed phenotypic analysis of circulating ILCs was performed at rest and immediately post-exercise. We show for the first time that a bout of high-intensity exercise is associated with an influx of ILCs that are traditionally regarded as tissue-resident. In addition, this is the first study to highlight that latent CMV infection blunts the exercise-response of total ILCs and progenitor ILCs (ILCPs). These promising data suggest that acute exercise facilitates the circulation of certain ILC subsets, further advocating for the improvements in health seen with exercise by enhancing cellular mobilization and immunosurveillance, while also highlighting the indirect deleterious effects of CMV infection in healthy adults.

Bilateral NIRS measurements of muscle mitochondrial capacity: Feasibility and repeatability.

BACKGROUND: Non-invasive determination of mitochondrial capacity via near infrared spectroscopy (NIRS) typically involves voluntary exercise of a single muscle group followed by as many as 26 brief ischemic cuff occlusions to determine a single recovery rate constant (k). PURPOSE: To determine the within- and between-visit repeatability of a shortened bilateral NIRS protocol, and to establish the feasibility of hamstring k measurements. METHODS: Sixteen young (eight women, eight men; 22 ± 3 years) active adults underwent a bilateral electrical stimulation protocol in which multiple (n = 4) measurements of k for the vastus lateralis (VL) and medial hamstring (MH) muscles were determined on two visits. Repeatability (CV% and intraclass correlations, ICC) and equivalency across visits were assessed for both muscles. RESULTS: Mean k values in the VL were consistent with published values and within-visit ICCs were moderately high for both muscles in both sexes. In men, average k values on visit 2 were within 1% (VL muscle) and 5% (MH muscle) of the values on visit 1 (all p > 0.78). In women, average k values were 10%-15% lower on visit 2 (p = 0.01 and p = 0.15 for MH and VL) with the largest between-visit differences in a subset of participants with the most days between visits. CONCLUSIONS: This bilateral NIRS protocol is time efficient and provides valid estimates of k in both sexes and muscle groups with acceptable within-visit repeatability. Lower than expected between-visit repeatability in some participants reinforces the need for further investigation of this newly developed protocol to identify and control for experimental and behavioral sources of variation.