Role of Gut Microbe Composition in Psychosocial Symptom Response to Exercise Training in Breast Cancer Survivors (ROME) study: protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is linked to gut microbial diversity and production of beneficial metabolites. Studies suggest that gut microbiota composition is a potential mechanism underlying fatigue response to exercise. Randomised controlled trials testing the effects of exercise on the gut microbiome are limited and there is a scarcity of findings specific to breast cancer survivors. The objective of this study is to determine if fitness-related modifications to gut microbiota occur and, if so, mediate the effects of aerobic exercise on fatigue response. METHODS AND ANALYSIS: The research is a randomised controlled trial among breast cancer survivors aged 18-74 with fatigue. The primary aim is to determine the effects of aerobic exercise training compared with an attention control on gut microbiota composition. The secondary study aims are to test if exercise training (1) affects the gut microbiota composition directly and/or indirectly through inflammation (serum cytokines), autonomic nervous system (heart rate variability) or hypothalamic-pituitary-adrenal axis mediators (hair cortisol assays), and (2) effects on fatigue are direct and/or indirect through changes in the gut microbiota composition. All participants receive a standardised controlled diet. Assessments occur at baseline, 5 weeks, 10 weeks and 15 weeks (5 weeks post intervention completion). Faecal samples collect the gut microbiome and 16S gene sequencing will identify the microbiome. Fatigue is measured by a 13-item multidimensional fatigue scale. ETHICS AND DISSEMINATION: The University of Alabama at Birmingham Institutional Review Board (IRB) approved this study on 15 May 2019, UAB IRB#30000320. A Data and Safety Monitoring Board convenes annually or more often if indicated. Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04088708.

Walking net V ˙ O2 rises with advancing age in older women: where to go from here?

PURPOSE: Walking net V ˙ O2 tends to increase with advancing age; however, factors contributing to this relationship have not been widely described. The implications of such findings could inform targeted strategies to promote independent mobility in older adults. Herein, we evaluated the relationship between net V ˙ O2 and age at two submaximal workloads while exploring potential moderators of this relationship. METHODS: Secondary analyses were performed on 35 older (65 ± 3 years) women who completed a battery of physical assessments including fixed-speed, non-graded and graded (+ 2.5%) treadmill walking with indirect calorimetry to determine net V ˙ O2. Maximal oxygen uptake ( V ˙ O2max), knee extensor maximal isometric voluntary contraction (MVC), peak rate of torque development (RTD), and plantar flexor range-of-motion (PFROM) were also measured. RESULTS: Bivariate correlations showed non-graded (r = 0.403, p = 0.017) and graded (r = 0.413, p = 0.014) net V ˙ O2 were positively related to age. Notably, these relationships strengthened after adjusting for V ˙ O2max. Regression modeling showed age, RTD:MVC ratio (composite of muscle performance), and PFROM together explained 49% and 34% of the variance in non-graded and graded net V ˙ O2, respectively. Further analyses suggested knee extensor MVC moderates the relationship between non-graded net V ˙ O2 and age, accounting for 9% of the variance [ΔR2 = 0.090, F (1,31) = 4.13, p = 0.05]. CONCLUSION: These data support the premise that, in older women, walking net V ˙ O2 rises with advancing age, and additionally, the RTD:MVC ratio and PFROM are independent correlates of non-graded net V ˙ O2. Exercise interventions with a high degree of training specificity including explosive, velocity-based elements may promote independent mobility in older women.

Grass-Fed and Non-Grass-Fed Whey Protein Consumption Do Not Attenuate Exercise-Induced Muscle Damage and Soreness in Resistance-Trained Individuals: A Randomized, Placebo-Controlled Trial.

Eccentric muscle contractions can cause structural damage to muscle cells resulting in temporarily decreased muscle force production and soreness. Prior work indicates pasture-raised dairy products from grass-fed cows have greater anti-inflammatory and antioxidant properties compared to grain-fed counterparts. However, limited research has evaluated the utility of whey protein from pasture-raised, grass-fed cows to enhance recovery compared to whey protein from non-grass-fed cows. Therefore, using a randomized, placebo-controlled design, we compared the effect of whey protein from pasture-raised, grass-fed cows (PRWP) to conventional whey protein (CWP) supplementation on indirect markers of muscle damage in response to eccentric exercise-induced muscle damage (EIMD) in resistance-trained individuals. Thirty-nine subjects (PRWP, n = 14; CWP, n = 12) completed an eccentric squat protocol to induce EIMD with measurements performed at 24, 48, and 72 h of recovery. Dependent variables included: delayed onset muscle soreness (DOMS), urinary titin, maximal isometric voluntary contraction (MIVC), potentiated quadriceps twitch force, countermovement jump (CMJ), and barbell back squat velocity (BBSV). Between-condition comparisons did not reveal any significant differences (p ≤ 0.05) in markers of EIMD via DOMS, urinary titin, MIVC, potentiated quadriceps twitch force, CMJ, or BBSV. In conclusion, neither PRWP nor CWP attenuate indirect markers of muscle damage and soreness following eccentric exercise in resistance-trained individuals.

Computational fluid dynamics of upper airway aerodynamics for exercise-induced laryngeal obstruction: A feasibility study.

Objective: Use of computational fluid dynamic (CFD) simulations to measure the changes in upper airway geometry and aerodynamics during (a) an episode of Exercise-Induced Laryngeal Obstruction (EILO) and (b) speech therapy exercises commonly employed for patients with EILO. Methods: Magnetic resonance imaging stills of the upper airway including the nasal and oral cavities from an adult female were used to re-construct three-dimensional geometries of the upper airway. The CFD simulations were used to compute the maximum volume flow rate (l/s), pressure (Pa), airflow velocity (m/s) and area of cross-section opening in eight planes along the vocal tract, separately for inhalation and exhalation. Results: Numerical predictions from three-dimensional geometrical modeling of the upper airway suggest that the technique of nose breathing for inhalation and pursed lip breathing for exhalation show most promising pressure conditions and cross-sectional diameters for rescue breathing exercises. Also, if EILO is due to the constriction at the vocal fold level, then a quick sniff may also be a proper rescue inhalation exercise. EILO affects both the inspiratory and the expiratory phases of breathing. Conclusions: A prior knowledge of the supraglottal aerodynamics and the corresponding upper airway geometry from CFD analysis has the potential to assist the clinician in choosing the most effective rescue breathing technique for optimal functional outcome of speech therapy intervention in patients with EILO and in understanding the pathophysiology of EILO on a case-by-case basis with future studies. Level of Evidence: 4.

Ecological Momentary Assessment of Midlife Adults' Daily Stress: Protocol for the Stress Reports in Variable Environments (STRIVE) App Study.

BACKGROUND: Daily stressors are associated with cognitive decline and increased risk of heart disease, depression, and other debilitating chronic illnesses in midlife adults. Daily stressors tend to occur at home or at work and are more frequent in urban versus rural settings. Conversely, spending time in natural environments such as parks or forests, or even viewing nature-themed images in a lab setting, is associated with lower levels of perceived stress and is hypothesized to be a strong stress "buffer," reducing perceived stress even after leaving the natural setting. However, many studies of daily stress have not captured environmental contexts and relied on end-of-day recall instead of in-the-moment data capture. With new technology, these limitations can be addressed to enhance knowledge of the daily stress experience. OBJECTIVE: We propose to use our novel custom-built Stress Reports in Variable Environments (STRIVE) ecological momentary assessment mobile phone app to measure the experience of daily stress of midlife adults in free-living conditions. Using our app to capture data in real time will allow us to determine (1) where and when daily stress occurs for midlife adults, (2) whether midlife adults' daily stressors are linked to certain elements of the built and natural environment, and (3) how ecological momentary assessment measurement of daily stress is similar to and different from a modified version of the popular Daily Inventory of Stressful Events measurement tool that captures end-of-day stress reports (used in the Midlife in the United States [MIDUS] survey). METHODS: We will enroll a total of 150 midlife adults living in greater Indianapolis, Indiana, in this study on a rolling basis for 3-week periods. As those in underrepresented minority groups and low-income areas have previously been found to experience greater levels of stress, we will use stratified sampling to ensure that half of our study sample is composed of underrepresented minorities (eg, Black, American Indian, Hispanic, or Native Pacific Islanders) and approximately one-third of our sample falls within low-, middle-, and high-income brackets. RESULTS: This project is funded by the National Institute on Aging from December 2022 to November 2024. Participant enrollment began in August 2023 and is expected to finish in July 2024. Data will be spatiotemporally analyzed to determine where and when stress occurs for midlife adults. Pictures of stressful environments will be qualitatively analyzed to determine the common elements of stressful environments. Data collected by the STRIVE app will be compared with retrospective Daily Inventory of Stressful Events data. CONCLUSIONS: Completing this study will expand our understanding of midlife adults' experience of stress in free-living conditions and pave the way for data-driven individual and community-based intervention designs to promote health and well-being in midlife adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51845.

Amenorrhea and oligomenorrhea risk related to exercise training volume and intensity: Findings from 3705 participants recruited via the STRAVA™ exercise application.

OBJECTIVES: To investigate associations between self-reported exercise training habits and amenorrhea/oligomenorrhea among physically active women. DESIGN: A cross-sectional survey was completed by 3705 women (median age = 40 years [quartile 1, quartile 3: 30, 45], body mass index = 22.1 kg/m2 [20.5, 24.2]) representing multiple nationalities and sports via the STRAVA™ exercise application. Respondents selected the amount of time they participated in low intensity, moderate intensity, and high intensity exercise training per week. Amenorrhea/oligomenorrhea was defined as self-reporting ≤10 menses in the last year. METHODS: Associations between weekly exercise volume for low intensity training, moderate intensity training, and high intensity training and amenorrhea/oligomenorrhea were modeled with univariate logistic regression models, followed by adjustment for age and body mass index. RESULTS: Amenorrhea/oligomenorrhea prevalence was 16 % (n = 576/3705), with no difference by country of origin or most sport modes. In adjusted models, participating in low intensity training ≥7 h/week or moderate intensity training ≥6 h/week was associated with 1.43 (95 % confidence interval: 1.04-1.96) and 1.46 (1.10-1.95) greater odds of amenorrhea/oligomenorrhea compared to 2 to 3 h/week, respectively. Similarly, high intensity training ≥5 h/week was associated with 1.41 (1.03-1.92) greater odds of amenorrhea/oligomenorrhea compared to 1 to 2 h/week. Participating in low intensity training for ≤30 min/week compared to 2 to 3 h/week was associated with reduced amenorrhea/oligomenorrhea odds (0.65 [0.44-0.94]). CONCLUSIONS: Taken together, these associations suggest greater weekly exercise volume, irrespective of intensity, may increase amenorrhea/oligomenorrhea risk among physically active women.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

Fluid balance during physical work in the heat is not modified by the menstrual cycle when fluids are freely available.

We tested the hypothesis that women may be more at risk of becoming dehydrated during physical work in the heat in the early follicular phase (EF), compared with the late follicular (LF) and mid-luteal (ML) phases of the menstrual cycle when allowed free access to drink. Twelve healthy, eumenorrheic, unacclimated women (26 ± 5 yr) completed three trials (EF, LF, and ML phases) involving 4 h of exposure to 33.8 ± 0.8 °C, 54 ± 1% relative humidity. Each hour, participants walked on a treadmill for 30 min at a rate of metabolic heat production of 338 ± 9 W. Participants drank a cool, flavor-preferred non-caloric sport drink ad libitum. Nude body weight was measured pre- and post-exposure, and percent changes in body weight loss were interpreted as an index of changes in total body water. Total fluid intake and urine output were measured and sweat rate was estimated from changes in body mass corrected for fluid intake and urine output. Fluid intake was not different between phases (EF: 1,609 ± 919 mL; LF: 1,902 ± 799 mL; ML: 1,913 ± 671; P = 0.202). Total urine output (P = 0.543) nor sweat rate (P = 0.907) differed between phases. Percent changes in body mass were not different between phases (EF: -0.5 ± 0.9%; LF: -0.3 ± 0.9%; ML: -0.3 ± 0.7%; P = 0.417). This study demonstrates that the normal hormonal fluctuations that occur throughout the menstrual cycle do not alter fluid balance during physical work in the heat.NEW & NOTEWORTHY The effect of the menstrual cycle on fluid balance during physical work in the heat when fluids are freely available is unknown. This study demonstrates that fluid balance is not modified in women across three distinct phases of the menstrual cycle during physical work in the heat These results indicate that when women have free access to cool fluid during physical work in the heat, they respond similarly across all three phases to maintain fluid homeostasis across the menstrual cycle.

Relative leg press strength relates to activity energy expenditure in older women: Implications for exercise prescription.

Limited work has evaluated how leg press strength (LPS), relative to body mass (i.e., rLPS), affects heart rate (HR) responses during activities of daily living. Such information would prove useful by informing a specific level of rLPS needed to promote independent mobility and physical activity. Secondary analyses were performed on baseline measures of 76 untrained older (65 ± 4 y) women. After familiarization, one-repetition maximum leg press was converted to rLPS by dividing the external load lifted (kg) by body mass (BM). Participants were stratified according to percentile of age-group norms of rLPS: ≤50 % (low, ≤0.99 kg/BM, n = 15), 51-89 % (middle, 1.0-1.31 kg/BM, n = 31), and ≥90 % (high, ≥1.32 kg/BM, n = 30). HR was measured at rest and during laboratory-based tasks including fixed-speed (0.89 m·s-1) non-graded treadmill walking, graded (2.5 %) treadmill walking, and stair stepping. Maximal oxygen uptake (V̇O2max) was measured via indirect calorimetry. Doubly labeled water was used to quantify activity energy expenditure (AEE) over a 14-d period. Relative LPS per group were: 0.85 ± 0.12 (low), 1.16 ± 0.09 (middle), and 1.55 ± 0.25 (high) (p < 0.001). Significant between-group differences in HR emerged during both walking tasks and stair stepping - with the high rLPS group having the lowest HR. AEE between-group comparisons did not yield statistical significance (p = 0.084), however, rLPS correlated with AEE (r = 0.234, p = 0.042) and V̇O2max (r = 0.430, p < 0.001). Such findings suggest a higher rLPS attenuates HR for weight-bearing activities while also demonstrating a significant, albeit modest, positive link to AEE among older women. This information may be especially relevant for informing thresholds of rLPS linked to mobility and functional independence in older women.

Functional Status, Mood State, and Physical Activity Among Women With Post-Acute COVID-19 Syndrome.

Objectives: While organ-specific pathophysiology has been well-described in SARS-CoV-2 infection, less is known about the attendant effects on functional status, mood state and leisure-time physical activity (PA) in post-acute COVID-19 syndrome (PASC). Methods: A case-control design was employed to recruit 32 women (n = 17 SARS-CoV-2; n = 15 controls) matched on age (54 ± 12 years) and body mass index (27 ± 6 kg/m2) that did not differ by smoking status or history of cardiopulmonary disease. Participants completed a series of assessments including Profile of Mood States (POMS), Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M), and Godin-Shephard Leisure-Time PA. Results: Significant between-group differences were detected for the POMS total mood disturbance with sub-scale analyses revealing elevated tension, confusion, and lower vigor among SARS-CoV-2 participants (all p-values < 0.05). The number of SARS-CoV-2 symptoms (e.g., loss of taste/smell, muscle aches etc.) were associated (r = 0.620, p = 0.008) with confusion. SARS-CoV-2 participants exhibited poorer functional status (p = 0.008) and reduced leisure-time PA (p = 0.004) compared to controls. Conclusion: The sequela of persistent SARS-CoV-2 symptoms elicit clear disturbances in functional status, mood state, and leisure-time PA among women with PASC. Ongoing symptom presentation affects recovery time-course and PA participation.

Estimation of sparse functional quantile regression with measurement error: a SIMEX approach.

Quantile regression is a semiparametric method for modeling associations between variables. It is most helpful when the covariates have complex relationships with the location, scale, and shape of the outcome distribution. Despite the method's robustness to distributional assumptions and outliers in the outcome, regression quantiles may be biased in the presence of measurement error in the covariates. The impact of function-valued covariates contaminated with heteroscedastic error has not yet been examined previously; although, studies have investigated the case of scalar-valued covariates. We present a two-stage strategy to consistently fit linear quantile regression models with a function-valued covariate that may be measured with error. In the first stage, an instrumental variable is used to estimate the covariance matrix associated with the measurement error. In the second stage, simulation extrapolation (SIMEX) is used to correct for measurement error in the function-valued covariate. Point-wise standard errors are estimated by means of nonparametric bootstrap. We present simulation studies to assess the robustness of the measurement error corrected for functional quantile regression. Our methods are applied to National Health and Examination Survey data to assess the relationship between physical activity and body mass index among adults in the United States.

Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls.

PURPOSE: Aging associated with progressive declines in physical function is well-known; however, it is unclear how breast cancer diagnosis affects the trajectories of physical function over a long period of time. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. METHODS: 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. RESULTS: We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~ 7 pounds shortly after breast cancer diagnosis, and then improved over time. CONCLUSION: Our study revealed that older breast cancer survivors relative to older women without cancer had significantly worse declines in grip strength and gait speed. Breast cancer survivors also had a sharp, short-term drop followed by gradual improvement over time in quadriceps strength. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.

Why obesity and psychological stress matter in recovery of post-acute sequelae of SARS-CoV-2.

Numerous elements of the COVID-19 pandemic have proven challenging to overcome. We now recognize a perplexing characteristic of SARS-CoV-2 features mixed, unresolving symptoms that can last 4 weeks or longer after initial diagnosis, termed post-acute sequelae of SARS-CoV-2 (PASC). Full recovery can thus become a protracted ordeal as conservative estimates indicate 20% of SARS-CoV-2 cases will develop PASC, with women at increased risk. Emerging evidence suggests latent virus reactivation including cytomegalovirus, Epstein-Barr virus, and/or varicella zoster virus may perpetuate the burden of PASC. This is problematic because immune dysfunction is linked to obesity and psychological stress, both of which disproportionately affect socioeconomically disadvantaged people and racial/ethnic minorities. Applying a patient-centered approach in which the principal factors guiding decision-making are based on the needs and abilities of the individual is essential. Still, the independent and combined influence of obesity and psychological stress on immune function necessitates due consideration in the context of PASC recovery.

ARTE index revisited: linking biomarkers of cardiometabolic health with free-living physical activity in postmenopausal women.

Activity-related energy expenditure (AEE) correlates with physical activity volume; however, between-person differences in body size and walking economy (net V̇o2) can influence AEE. The ratio of total energy expenditure (TEE) and resting energy expenditure (REE) estimates physical activity level (PAL) relative to body mass, yet does not account for variance in walking economy. The activity-related time equivalent (ARTEwalk) circumvents such constraints by adjusting for individual-specific walking economy. Herein, we compared AEE, PAL, and ARTEwalk index in a cohort (n = 81) of postmenopausal women while examining possible associations with biomarkers of cardiometabolic health. Secondary analyses were performed on postmenopausal women dichotomized above/below age group 50th percentile for body fat percent. TEE was reduced by 10% for the thermogenesis of digestion wherein AEE was calculated by subtracting REE from adjusted TEE. PAL was calculated as the ratio of TEE/REE. AEE was divided by the mean net energy expenditure of nongraded walking to calculate the ARTEwalk index. Between-group differences were not detected for AEE or PAL. However, the ARTEwalk index revealed that participants with less adiposity were more physically active (258 ± 149 vs. 198 ± 115 min·day-1; P = 0.046; g = 0.46). AEE and PAL did not correlate with cardiorespiratory fitness or biomarkers of cardiometabolic health. Cardiorespiratory fitness (r = 0.32), arterial elasticity (r = 0.24), total cholesterol/HDL-c ratio (r = -0.22), and body fat% (r = -0.24) were correlated with ARTEwalk. The ARTEwalk index may offer utility in detecting possible differences in physical activity volume among postmenopausal women and appears better associated with cardiometabolic biomarkers compared with AEE or PAL.

Functional status, mood state, and physical activity among women with post-acute COVID-19 syndrome.

OBJECTIVES: While organ-specific pathophysiology has been well-described in SARS-CoV-2 infection, less is known about the attendant effects on functional status, mood state and leisure-time physical activity (PA) in post-acute COVID-19 syndrome. METHODS: A case-control design was employed to recruit 32 women ( n = 17 SARS-CoV-2; n = 15 controls) matched on age (54 ± 12 years), body mass index (27 ± 6 kg/m 2 ), smoking status, and history of cardiopulmonary disease. Participants completed a series of assessments including the Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M), Profile of Mood States (POMS), and Godin-Shephard Leisure-Time PA. RESULTS: SARS-CoV-2 participants exhibited poorer functional status ( p = 0.008) and reduced leisure-time PA ( p = 0.004) compared to controls. Significant between-group differences were also detected for the POMS total mood disturbance with sub-scale analyses revealing elevated tension, confusion, and lower vigor among SARS-CoV-2 participants (all p -values < 0.05). The number of SARS-CoV-2 symptoms (e.g., loss of taste / smell, muscle aches etc.) were associated ( r = 0.620, p = 0.008) with confusion. CONCLUSION: The sequela of persistent SARS-CoV-2 symptoms elicit clear disturbances in functional status, mood state, and leisure-time PA among women with post-acute COVID-19 syndrome.

Evidence for impaired chronotropic responses to and recovery from 6-minute walk test in women with post-acute COVID-19 syndrome.

NEW FINDINGS: What is the central question of this study? Are chronotropic responses to a 6-minute walk test different in women with post-acute coronavirus disease 2019 (COVID-19) syndrome compared with control subjects? What is the main finding and its importance? Compared with control subjects, the increase in heart rate was attenuated and recovery delayed after a 6-minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Such alterations have potential to constrain not only exercise tolerance but also participation in free-living physical activity in women during post-acute recovery from COVID-19. ABSTRACT: The short-term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well defined. However, the implications of cardiopulmonary sequelae, persisting beyond acute illness, on physical function are largely unknown. Herein, we characterized heart rate responses to and recovery from a 6-minute walk test (6MWT) in women ∼3 months after mild-to-moderate SARS-CoV-2 infection compared with non-infected control subjects. Forty-five women (n = 29 SARS-CoV-2; n = 16 controls; age = 56 ± 11 years; body mass index = 25.8 ± 6.0 kg/m2 ) completed pulmonary function testing and a 6MWT. The SARS-CoV-2 participants demonstrated reduced total lung capacity (84 ± 8 vs. 93 ± 13%; P = 0.006), vital capacity (87 ± 10 vs. 93 ± 10%; P = 0.040), functional residual capacity (75 ± 16 vs. 88 ± 16%; P = 0.006) and residual volume (76 ± 18 vs. 93 ± 22%; P = 0.001) compared with control subjects. No between-group differences were observed in 6MWT distance (P = 0.194); however, the increase in heart rate with exertion was attenuated among SARS-CoV-2 participants compared with control subjects (+52 ± 20 vs. +65 ± 18 beats/min; P = 0.029). The decrease in heart rate was also delayed for minutes 1-5 of recovery among SARS-CoV-2 participants (all P < 0.05). Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS-CoV-2 participants not actively experiencing these symptoms. Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS-CoV-2 infection.

Moving beyond inclusion: Methodological considerations for the menstrual cycle and menopause in research evaluating effects of dietary nitrate on vascular function.

Recent reports have acknowledged the underrepresentation of women in the field of dietary nitrate (NO3-) research. Undoubtedly, greater participation from women is warranted to clarify potential sex differences in the responses to dietary NO3- interventions. However, careful consideration for the effects of sex hormones - principally 17ß-estradiol - on endogenous nitric oxide (NO) synthesis and dietary NO3- reductase capacity is necessary for improved interpretation and reproducibility of such investigations. From available literature, we present a narrative review describing how hormonal variations across the menstrual cycle, as well as with menopause, may impact NO biosynthesis catalyzed by NO synthase enzymes and NO3- reduction via the enterosalivary pathway. In doing so, we address methodological considerations related to the menstrual cycle and hormonal contraceptive use relevant for the inclusion of premenopausal women along with factors to consider when testing postmenopausal women. Adherence to such methodological practices may explicate the utility of dietary NO3- supplementation as a means to improve vascular function among women across the lifespan.

Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.

BACKGROUND: Previous narrative reviews have concluded that dietary nitrate (NO3-) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3- on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3- supplementation on human muscle power. METHODS: The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3- on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. RESULTS: Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10- 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10- 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10- 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). CONCLUSIONS: Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.