Optimization of mHealth behavioral interventions for patients with chronic lymphocytic leukemia: the HEALTH4CLL study.

PURPOSE: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL). METHODS: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in outcomes from baseline to follow-up among patients. Factorial analysis of variance examined effective intervention components and their combinations regarding improvement in fatigue and PF scores. RESULTS: Among 31 patients, we observed significant improvements in fatigue (+ 11.8; t = 4.08, p = 0.001) and PF (+ 2.6; t = 2.75, p = 0.01) scores. The combination of resistance and aerobic exercise with daily self-monitoring was associated with improved fatigue scores (ß = 3.857, SE = 1.617, p = 0.027). Analysis of the individual components of the MOST design demonstrated greater improvement in the PF score with resistance plus aerobic exercise than with aerobic exercise alone (ß = 2.257, SE = 1.071, p = 0.048). CONCLUSIONS: Combined aerobic and resistance exercise and daily self-monitoring improved PF and reduced fatigue in patients with CLL. IMPLICATIONS FOR CANCER SURVIVORS: This pilot study supported the feasibility of a low-touch mHealth intervention for survivors of CLL and provided preliminary evidence that exercising, particularly resistance exercise, can improve their symptoms and quality of life.

Exercise Training Improves Brachial Artery Endothelial Function, but Does Not Alter Inflammatory Biomarkers in Patients with Peripheral Artery Disease: a Systematic Review and Meta-analysis.

The study aimed to systematically review the effects of exercise training (EX) on brachial artery flow-mediated dilation (FMD) and inflammatory biomarkers in patients with peripheral artery disease (PAD). Five electronic databases were searched: (i) patients with PAD aged ≥ 18; (ii) structured EX ≥ 2 weeks; (iii) measured brachial artery FMD; and (iv) measured blood inflammatory biomarkers. Eighteen studies met the inclusion criteria. EX increased FMD but had no effect on C-reactive protein, interleukin-6, and tumor necrosis factor-α. Subgroups with moderate intensity had a greater increase in FMD than subgroups with vigorous intensity. There was no difference in effect on FMD and three inflammatory biomarkers between subgroups training for ≤ 12 weeks and > 12 weeks of EX, < 50 min and ≥ 50 min of session duration, and < 150 min and ≥ 150 min of weekly volume, respectively. These results suggest that EX-induced improvement in vascular function can be independent of the improvement of systemic inflammation.

Objective and subjective sleep patterns and biomarkers of stress among women with a history of sexual abuse in childhood.

OBJECTIVE: Childhood sexual abuse (CSA) is associated with posttraumatic stress symptoms (PTSSs) and sleep disturbance into adulthood. The latter is thought to emerge from dysregulation in biobehavioral systems, including nighttime hyperarousal; however, studies investigating specific mechanisms to explain these long-term sleep problems are limited. The present study examined presleep arousal, fear of sleep, and the cortisol awakening response (CAR) as putative mediators between PTSS and sleep disturbance in women with a history of CSA. METHOD: N = 64 cis-gendered women with a self-reported history of CSA completed a baseline diagnostic interview, self-reported mental health and sleep measures, 7 days of actigraphy monitoring with concurrent sleep diary, and 2 days of saliva sampling. RESULTS: PTSSs were not significantly associated with actigraphy-estimated sleep variables but were positively associated with self-reported sleep onset latency (SOL) and negatively associated with self-reported sleep quality. Similarly, PTSSs were not significantly associated with CAR but were associated with higher presleep arousal and fear of sleep ratings. Mediational models identified greater presleep cognitive arousal to partially explain the PTSS-SOL relationship. Specific features of CSA (i.e., age at time of abuse, location of abuse, relationship to the perpetrator) did not moderate this association. CONCLUSION: Findings suggest that targeting maladaptive cognitions (e.g., worries, rumination) that occur during the presleep period may be a potential intervention target in mitigating sleep disturbance and PTSSs in this population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation.

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of MHC class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, "mimicked" the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared with wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes. See related Spotlight by Betof Warner, p. 1158.

A Scoping Review on the Effects of Physical Exercise and Fitness on Peripheral Leukocyte Energy Metabolism in Humans.

Background: Both acute and chronic exercise have profound effects on systemic metabolism and the immune system. While acute exercise transiently disturbs energy homeostasis and elicits acute inflammation, exercise training improves systemic metabolic capacity, lowers basal inflammation, and reduces infection risk. Accordingly, accumulating evidence indicates links between systemic and immune cell metabolism and suggests that cellular metabolism may be an important way exercise influences immune function. Yet, no reviews have systematically surveyed the literature in this area. Aims: The aims of this scoping review were to collect, summarize, and provide descriptive analysis of literature on the effects of acute exercise, chronic exercise, and physical fitness on peripheral leukocyte energy metabolism of human adults. Methods: Reports were retrieved from the databases Pubmed, Scopus, and Embase and hierarchically filtered for eligibility. Eligible reports were those that implemented acute or chronic exercise interventions, or assessed physical fitness, in relation to the regulation or function of leukocyte energy metabolism in human adults. Data were charted from eligible reports by two independent reviewers, confirmed by conference, and organized for reporting. Results & Conclusion: Results suggest acute exercise can influence the regulation and function of leukocyte metabolism, with some similarities to what has been previously documented in skeletal muscle. Data also evidence that exercise training and/ or physical fitness alters cellular metabolic regulation and function. Improvements in markers of cell respiratory function or mitochondrial regulation were frequently observed following training or with greater fitness. However, notable gaps in the literature remain. These gaps include: the effects of acute exercise and exercise training on leukocyte glycolysis, the effects of resistance and concurrent exercise, and potential differences in the effects of exercise between immune cell types and subsets. Future research is encouraged to fill the latter gaps and further delineate how exercise influences the immune system and can be used to support overall health.

Characterization of transitional memory CD4+ and CD8+ T-cell mobilization during and after an acute bout of exercise.

T-cell subsets, including naïve (NA), central memory (CM), transitional memory (TM), effector memory (EM), and RA + effector memory (EMRA), differ in phenotype and function. T-cells are mobilized by exercise, with differences in the magnitude of mobilization between subsets. However, the response of TM T-cells to exercise has not yet been described. Further, T-cells expressing the late differentiation marker CD57 are known to be highly responsive to exercise, but the relative response of CD57 + and CD57- within T-cell subsets is unknown. We therefore aimed to characterize the exercise-induced mobilization of TM T-cells, as well as to compare the exercise response of CD57 + and CD57- cells within T-cell subsets. Methods: Seventeen participants (7 female; aged 18-40 years) cycled 30 min at 80% of their estimated maximum heart rate. Venous blood obtained pre, post, and 1H post-exercise was analyzed by flow cytometry. CD45RA, CCR7, and CD28 expression within CD4 + and CD8+ T-cells identified NA, CM, TM, EM, and EMRA subsets. CD57 expression within EM, EMRA, and CD28+ T-cells was also quantified. The relative mobilization of each subset was compared by calculating fold change in cell concentration during (ingress, post/pre) and after exercise (egress,1H post/post). Cytomegalovirus (CMV) serostatus was determined by ELISA and was considered in models. Results: TM CD8+ T-cell concentration was greater post-exercise than pre-exercise (138.59 ± 56.42 cells/µl vs. 98.51 ± 39.68 cells/µl, p < 0.05), and the proportion of CD8 + with a TM phenotype was elevated 1H post-exercise (1H: 32.44 ± 10.38% vs. Pre: 30.15 ± 8.77%, p < 0.05). The relative mobilization during and after exercise of TM T-cells did not differ from NA and CM but was less than EM and EMRA subsets. Similar results were observed within CD4+ T-cells. CD57 + subsets of CD28+ T-cells and of EM and EMRA CD8+ T-cells exhibited a greater relative mobilization than CD57- subsets (all p < 0.05). Conclusion: These results indicate TM CD4 + and CD8+ T-cells are transiently mobilized into the blood with exercise, but not to as great of an extent as later differentiated EM and EMRA T-cells. Results also indicate CD57 identifies highly exercise responsive cells within CD8+ T-cell subsets.

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice.

Background: Every bout of exercise mobilizes and redistributes large numbers of effector lymphocytes with a cytotoxic and tissue migration phenotype. The frequent redistribution of these cells is purported to increase immune surveillance and play a mechanistic role in reducing cancer risk and slowing tumor progression in physically active cancer survivors. Our aim was to provide the first detailed single cell transcriptomic analysis of exercise-mobilized lymphocytes and test their effectiveness as a donor lymphocyte infusion (DLI) in xenogeneic mice engrafted with human leukemia. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from healthy volunteers at rest and at the end of an acute bout of cycling exercise. Flow cytometry and single-cell RNA sequencing was performed to identify phenotypic and transcriptomic differences between resting and exercise-mobilized cells using a targeted gene expression panel curated for human immunology. PBMCs were injected into the tail vein of xenogeneic NSG-IL-15 mice and subsequently challenged with a luciferase tagged chronic myelogenous leukemia cell line (K562). Tumor growth (bioluminescence) and xenogeneic graft-versus-host disease (GvHD) were monitored bi-weekly for 40-days. Results: Exercise preferentially mobilized NK-cell, CD8+ T-cell and monocyte subtypes with a differentiated and effector phenotype, without significantly mobilizing CD4+ regulatory T-cells. Mobilized effector lymphocytes, particularly effector-memory CD8+ T-cells and NK-cells, displayed differentially expressed genes and enriched gene sets associated with anti-tumor activity, including cytotoxicity, migration/chemotaxis, antigen binding, cytokine responsiveness and alloreactivity (e.g. graft-versus-host/leukemia). Mice receiving exercise-mobilized PBMCs had lower tumor burden and higher overall survival (4.14E+08 photons/s and 47%, respectively) at day 40 compared to mice receiving resting PBMCs (12.1E+08 photons/s and 22%, respectively) from the same donors (p<0.05). Human immune cell engraftment was similar for resting and exercise-mobilized DLI. However, when compared to non-tumor bearing mice, K562 increased the expansion of NK-cell and CD3+/CD4-/CD8- T-cells in mice receiving exercise-mobilized but not resting lymphocytes, 1-2 weeks after DLI. No differences in GvHD or GvHD-free survival was observed between groups either with or without K562 challenge. Conclusion: Exercise in humans mobilizes effector lymphocytes with an anti-tumor transcriptomic profile and their use as DLI extends survival and enhances the graft-versus-leukemia (GvL) effect without exacerbating GvHD in human leukemia bearing xenogeneic mice. Exercise may serve as an effective and economical adjuvant to increase the GvL effects of allogeneic cell therapies without intensifying GvHD.

Relationships between T-lymphocytes and physical function in adults with chronic lymphocytic leukemia: Results from the HEALTH4CLL pilot study.

OBJECTIVE: Examine physical function and T-cell phenotype in patients with chronic lymphocytic leukemia (CLL) before and after a physical activity (PA) intervention. METHODS: Physical function measures and blood samples were collected from CLL patients (Rai stage 0-4, 50% receiving targeted therapy, N = 24) enrolled in a 16-week intervention of at-home aerobic and/or resistance exercise. Flow cytometry characterized T-cells in cryopreserved peripheral blood cells. Wilcoxon signed-rank test compared physical function and T-cell phenotype at baseline and 16-weeks; Kendall's Tau assessed associations between variables. RESULTS: Godin leisure-time PA score increased from baseline to 16-weeks (mean difference: 14.61, p < .01) and fatigue decreased (mean difference: 6.71, p < .001). At baseline, lower fatigue correlated with a lower proportion of CD8+ T-cells (τ = 0.32, p = .03) and cardiorespiratory fitness (CRF) inversely correlated with the percentage of PD-1+CD8+ T-cells (τ -0.31, p = .03). At 16-weeks, CRF inversely correlated with the proportion of PD-1+CD4+ T-cells (τ -0.34, p = .02). Reduced fatigue at 16-weeks correlated with an increased CD4:CD8 ratio (τ = 0.36, p = .02) and lower percentage of HLA-DR+PD-1+CD4+ T-cells (τ = -0.37, p = .01). CONCLUSIONS: This intervention increased leisure-time PA and decreased fatigue in CLL patients. These changes correlated with an increased CD4:CD8 T-cell ratio and reduced proportion of T-cells subsets previously associated with poor outcomes in CLL patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02194387.

Comparison of three exercise interventions with and without gemcitabine treatment on pancreatic tumor growth in mice: No impact on tumor infiltrating lymphocytes.

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice. Methods: Male C57BL/6 mice (6-8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran at 12 m/min for 45 min and LVCE for 15 min, 5 days/week. HIIT ran 1-min at 20 m/min, followed by 1-min walking at 8 m/min for 20 total intervals, 3 days/week. SED did not run. Additional sets of inoculated mice were assigned to the exercise interventions but did not receive gemcitabine. Tumor volume was measured every other day for 2 weeks; tumor-infiltrating lymphocytes were assessed by flow cytometry 3-week post-inoculation. Results: Tumor growth did not differ between groups that received gemcitabine (F(3, 34) = 1.487; p = 0.235; η2 = 0.116). In contrast, tumor growth differed between groups not provided gemcitabine (F(3,14) = 3.364; p = 0.049, η2 = 0.419), with trends for slower growth in LVCE than SED (p = 0.088) and HIIT (p = 0.084). Groups did not differ in tumor infiltrating lymphocytes. Conclusion: Contrary to our hypotheses, the exercise interventions compared here did not further reduce pancreatic tumor growth beyond that provided by gemcitabine. However, in mice not receiving gemcitabine, there was a trend for reduced tumor growth in LVCE.

T-cell counts in response to acute cardiorespiratory or resistance exercise in physically active or physically inactive older adults: a randomized crossover study.

T cells often undergo age-related changes, which may be offset by regular exercise training. However, the majority of literature is derived from cardiorespiratory exercise studies. The purpose of this study was to examine the effects of acute cardiorespiratory exercise and acute resistance exercise on the T-cell response among physically active (PA) older adults compared with physically inactive (PI) older adults. Twenty-four healthy older adults [PA n = 12; PI n = 12; means ± SD; age (years) PA 62 ± 5, PI 64 ± 5; body mass index (BMI; kg/m2) PA 23.9 ± 3.0, PI 25.6 ± 3.5] completed one bout each of matched intensity cardiorespiratory exercise and resistance exercise in a randomized order. Blood samples drawn preexercise, postexercise, and 1 h postexercise (recovery) were analyzed by flow cytometry for T cells and T-cell subsets. Resistance exercise mobilized more T-cell subsets in PI (10 of the measured types, including total T cells; CD45RA+ CD62L+, CD45RA- CD62L+, CD45RA- CD62L-, and CD45RA+ CD62L- T cells), whereas cardiorespiratory exercise mobilized more subsets in PA (CD45RA+ CD62L- and CD57+ CD45RA+ CD62L- CD4+ T cells). Both cardiorespiratory exercise and resistance exercise elicited a significant (P < 0.05) mobilization of highly differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T cells into the circulation postexercise in both PA and PI groups. Furthermore, cardiorespiratory exercise resulted in a decrease in the number of circulating Th17 cells postexercise, whereas resistance exercise increased Th17 cell mobilization compared with the cardiorespiratory exercise response. There are differences between cardiorespiratory exercise and resistance exercise on the immune responses of T cells, particularly in PI individuals. This research study was registered at clinicaltrials.gov NCT03794050. NEW & NOTEWORTHY A bout of resistance exercise did not elicit the same T-cell responses as a bout of walking on a treadmill, and the response was also not the same for people who participate in regular exercise compared with those who do not. Although there were several similarities, these potential differences underscore the importance of careful selection of exercise protocol based on the population studied and the desired T-cell response to exercise outcome.

Effect of exercise on pancreatic cancer patients during treatment: a scoping review of the literature.

INTRODUCTION: Exercise can lower the risk of developing pancreatic cancer and has the potential to improve physical fitness and quality of life in patients with the disease. Yet, the effects of exercise training during pancreatic cancer treatment remain poorly characterized. This hampers the development of evidence-based disease-specific exercise recommendations. PURPOSE: The purpose of this review was to describe and interpret the effect of exercise on physiological, QoL, and cancer-specific outcomes reported in clinical trials among pancreatic cancer patients during treatment. METHODS: We conducted a scoping review of the literature according to the framework proposed by Arksey and O'Malley. Articles published prior to December 2021 were retrieved from PubMed, EMBASE, and Scopus. We only included studies that prescribed structured cardiorespiratory and/or resistance exercise in pancreatic cancer patients undergoing treatment. RESULTS: A total of 662 references were retrieved, of which 24 are included in the review. Twelve articles were randomized controlled trials and 12 were single-arm trials. Overlap in the trials from which data were reported occurred in 16 articles. Moderate intensity exercise was most commonly prescribed, reported feasible for most patients, with potential to enhance physical fitness and QoL. However, exercise adherence and beneficial effects may diminish with disease progression. Limited evidence suggests exercise may benefit cancer-specific outcomes. CONCLUSION: The results of this review indicate that exercise is feasible during pancreatic cancer treatment. Exercise can also improve physical fitness and QoL. However, its beneficial effects may fall with advanced disease and more rigorous research is needed to develop precise exercise protocols for this population.

Physical activity during the SARS-CoV-2 pandemic is linked to better mood and emotion.

The SARS-CoV-2 pandemic may negatively impact mood and emotion. Physical activity may protect against mood disturbance and promote positive affect. This study asked if physical activity before, during, or the change in physical activity with the pandemic, impacted affect and mood during the pandemic. US adult residents (18-74 years; N = 338) were surveyed from 29 April to 3 June 2020. Physical activity before and during the pandemic was assessed with the Physical Activity Rating survey. The Positive and Negative Affect Schedule measured affect and the Profile of Moods Questionnaire assessed mood. Comparisons between physically inactive and active participants by Analysis of Covariance found greater vigour in participants classed as physically active before the pandemic. Positive affect, vigour and esteem-related affect were greater in participants physically active during the pandemic. Multiple linear regression revealed relationships between the change in physical activity and mood. Change in physical activity positively associated with positive affect (b = 1.06), esteem-related affect (b = 0.33) and vigour (b = 0.53), and negatively associated with negative affect (b = -0.47), total mood disturbance (b = -2.60), tension (b = -0.31), anger (b = -0.24), fatigue (b = -0.54), depression (b = -0.50) and confusion (b = -0.23). These data demonstrate that physical activity during the pandemic, and increased physical activity relative to before the pandemic, related to better mood.

Single-Arm 8-Week Ad Libitum Self-Prepared Paleo Diet Reduces Cardiometabolic Disease Risk Factors in Overweight Adults.

The paleo diet is popular among the general population due to promoted weight loss and disease prevention benefits. We examined the effectiveness of a self-administered paleo diet in improving cardiometabolic disease risk factors. Overweight, physically inactive but otherwise healthy adults (males = 4, females = 3, age 32.7 ± 4.9 years, body mass index [BMI] 29.4 ± 2.4 kg/m2) habitually eating a traditional Western diet (1853.4 ± 441.2 kcal; 34.0% carbohydrate; 41.4% fat; 19.2% protein) completed an ad libitum self-administered paleo diet for 8 weeks. Height, weight, blood pressure, and a fasting blood sample were collected pre- and post-paleo dietary intervention. Blood samples were analyzed for fasting cardiometabolic disease biomarkers-including brain-derived neurotropic factor (BDNF), fibroblast growth factor (FGF) 21, and leptin. After 8 weeks, body mass (-5.3 kg, P = .008), BMI (-1.7 kg/m2, P = .002), serum leptin (-56.2%, P = .012), serum FGF21 (-26.7%, P = .002), and serum BDNF (-25.8%, P = .045) significantly decreased. Systolic and diastolic blood pressure were unchanged following the paleo dietary intervention (P > .05). Average energy intake (-412.6 kcal, P = .016) significantly decreased with the paleo dietary intervention mostly due to a reduction in carbohydrate consumption (-69.2 g; P = .003). An 8-week self-administered paleo dietary intervention was effective in improving cardiometabolic disease risk factors in a healthy, physically inactive overweight adult population.

No Effect of Acute Eccentric Resistance Exercise on Immune Responses to Influenza Vaccination in Older Adults: A Randomized Control Trial.

INTRODUCTION: Older adults are at elevated risk for morbidity and mortality caused by influenza. Vaccination is the primary means of prophylaxis, but protection is often compromised in older adults. As resistance exercise mobilizes immune cells into muscle, it may enhance vaccination response. PURPOSE: Compare antibody and cell mediated immune responses to influenza vaccination in older adults who performed eccentric resistance exercise immediately prior to vaccination to those who did not exercise. METHODS: Twenty nine resistance training-naive older adults (20 women, 73.9 ± 5.3 years) were randomized to 1 of 3 groups: vaccination in the same arm that exercised (Ex-S), vaccination in the opposite arm that exercised (Ex-Op), and seated rest (No-Ex). Exercise consisted of 10 sets of 5 eccentric unilateral repetitions at 80% of the pre-determined concentric one repetition maximum. Lateral raises were alternated with bicep curls. No-Ex sat quietly for 25 min. Following exercise or rest, all received the 2018 quadrivalent influenza vaccine (Seqirus Afluria) in the non-dominant deltoid. Antibody titers against each influenza vaccine strain were determined by hemagglutinin inhibition assays at baseline, 6-, and 24-weeks post-vaccination. Influenza-specific T cells were quantified after stimulation with the vaccine by intracellular cytokine staining. RESULTS: No significant group x time effects were found in antibody responses to any strain (interaction for A/H1N1: p = 0.682; A/H3N2: p = 0.644; B/Colorado/06/2017: p = 0.262; B/Phuket/3073/2013: p = 0.851). Groups did not differ in fold-increase of antibody titers 6- and 24-weeks post-vaccination. Influenza-specific T-cells did not differ between groups at any time (comparison at baseline: p = 0.985; 6-weeks: p = 0.889; 24 weeks: p = 0.857). One subject (Ex-S) reported flu-like symptoms 18 weeks post-vaccination. CONCLUSION: Acute arm eccentric exercise did not influence antibody titers or cell mediated immune responses to the influenza vaccine delivered post-exercise in older adults. More strenuous exercise may be required for exercise to act as an adjuvant. ClinicalTrials.gov Identifier: NCT03736759.

A Short-Term Paleolithic Dietary Intervention Does Not Alter Adipokines Linked to Adiposity.

The Paleolithic diet, characterized by an emphasis on hunter-gatherer type foods accompanied by an exclusion of grains, dairy products, and highly processed food items, is often promoted for weight loss and a reduction in cardiometabolic disease risk factors. Specific adipokines, such as adiponectin, omentin, nesfatin, and vaspin are reported to be dysregulated with obesity and may respond favorably to diet-induced fat loss. We aimed to evaluate the effects of an eight-week Paleolithic dietary intervention on circulating adiponectin, omentin, nesfatin, and vaspin in a cohort of physically inactive, but otherwise healthy adults. METHODS: Seven inactive adults participated in eight weeks of adherence to the Paleolithic Diet. Fasting blood samples, anthropometric, and body composition data were collected from each participant pre-and post-intervention. Serum adiponectin, omentin, nesfatin, and vaspin were measured. RESULTS: After eight weeks of following the Paleolithic diet, there were reductions (p<0.05) in relative body fat (-4.4%), waist circumference (- 5.9 cm), and sum of skinfolds (-36.8 mm). No changes were observed in waist to hip ratio (WHR), or in adiponectin, omentin, and nesfatin (p>0.05), while serum vaspin levels for all participants were undetectable. CONCLUSIONS: It is possible that although eight weeks resulted in modest body composition changes, short-term fat loss will not induce changes in adiponectin, omentin, and nesfatin in apparently healthy adults. Larger, long-term intervention studies that examine Paleolithic diet-induced changes across sex, body composition, and in populations with metabolic dysregulation are warranted.

Evaluation of the Role of Leisure Time Physical Activity and Sedentary Behavior Simultaneously on the Income-Overweight/Obesity Relationship.

In the United States, overweight/obesity is more prevalent among those with low-income; higher income is related to greater leisure time physical activity (LTPA) and sedentary behavior (SB), which are inversely related to overweight/obesity. This study aimed to evaluate the role of LTPA and SB simultaneously in the income-overweight/obesity relationship. Cross-sectional data from the National Health and Nutrition Examination Survey (2007-2014) were utilized (n = 10,348 non-older adults (aged 20-59 years)). A multiple mediator structural equation model was conducted to evaluate the indirect effects from income to overweight/obesity (Body Mass Index ≥25 kg/m2) through LTPA and SB simultaneously, controlling for confounding variables, including diet, smoking, and alcohol consumption. As expected, greater income was negatively associated with overweight/obesity. Income indirectly influenced overweight/obesity through LTPA (Indirect effect: B = -0.005; CI = -0.01, -0.003), and through SB (Indirect effect: B = 0.008; CI = 0.005, 0.01), in opposing directions. The direct effect from income to overweight/obesity remained statistically significant. LTPA partially accounted for the negative relationship between income and overweight/obesity; SB reduced the strength of the negative relationship between income and overweight/obesity. Targeted behavior approaches for weight management may be beneficial. Increasing LTPA among adults with lower income and decreasing SB among adults with higher income may provide some overweight/obesity protection.

Bidirectional relationships between sleep and biomarkers of stress and immunity in youth.

Insufficient sleep during childhood can lead to physical and mental health issues. In adults, sleep disturbances have been associated with altered levels of stress hormones and inflammatory cytokines, but data in youth is lacking. The aim of this study was to explore relationships between objective measures of sleep and salivary biomarkers in children and adolescents. Participants (N = 55, aged 8-16 years, 53% female) wore an actigraph sleep monitor in their home for seven nights and completed sleep diaries and the School Sleep Habits Survey (SSHS). Participants also donated first waking saliva samples, which were later assayed for α-amylase (sAA), cortisol, interleukin (IL)-6, and IL-1ß. While sAA was not associated with objective sleep it did show a positive association with self-reported sleep disturbance. Morning cortisol levels were associated with objective sleep variables, including minutes spent awake the night before sampling, and sleep efficiency and awakenings the night after sampling. Morning IL-6 was associated with prior night sleep efficiency and minutes spent awake the night after saliva sampling. Likewise, IL-1ß levels were associated with sleep duration and sleep onset latency during the nighttime sleep period prior to and after saliva sampling. These results align with other data to indicate objective elements of sleep are related to salivary cortisol, IL-6, and IL-1ß in youth. Thus, quality of sleep on the night prior to sampling should be considered when investigating levels of salivary mediators in children.

The effects of ß1 and ß1+2 adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: implications for cellular therapy and the anti-viral immune effects of exercise.

The adoptive transfer of donor-derived virus-specific T cells (VSTs) is an effective treatment for infections following allogeneic hematopoietic cell transplantation. Acute exercise mobilizes effector lymphocytes and VSTs to the circulation and augments the ex vivo manufacture of VSTs. This study determined if ß2 adrenergic receptor (AR) signaling precipitated the VST response to acute exercise. Healthy participants (n = 12) completed 30 min of steady-state cycling exercise after ingesting a placebo, a ß1 + 2 AR antagonist (nadolol) or a ß1 AR antagonist (bisoprolol). Circulating VSTs to cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV) antigens were enumerated before and after exercise, and peripheral blood mononuclear cells were cultured with viral peptides for 8 days to expand multi-VSTs. Compared with placebo, nadolol blunted the exercise-induced mobilization of CMV-VSTs (Δ VSTs/100,000 CD3+ T cells = 93 ± 104 vs. 22 ± 91 for placebo and nadolol, respectively; p = 0.036), while bisoprolol did not, despite both drugs evoking similar reductions in exercising heart rate and blood pressure. Circulating AdV and EBV VSTs (VSTs/mL blood) only increased after exercise with placebo. Although not significant, nadolol partially mitigated exercise-induced increases in multi-VST expansion, particularly in participants that demonstrated an exercise-induced increase in VST expansion. We conclude that exercise-induced enhancements in VST mobilization and expansion are at least partially ß2 AR mediated, thus highlighting a role for the ß2 AR in targeted therapy for the augmentation of VST immune cell therapeutics in the allogeneic adoptive transfer setting. Moreover, long-term regular exercise may provide additional viral protection in the host through frequent ß2 AR-dependent mobilization and redistribution of VSTs cumulated with each bout of exercise.

Vascular Protection by Exercise in Obesity: Inflammasome-associated Mechanisms.

PURPOSE: The nodlike receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical player in vascular pathology as it regulates caspase-1-mediated interleukin (IL)-1ß processing. Physical activity ameliorates obesity-induced inflammation and vascular dysfunction, but the mechanisms responsible for these positive changes are incompletely understood. Here, the protective effect of physical activity on the inflammasome-associated vascular dysfunction in obesity and its putative mechanisms were investigated. METHODS: Mice were fed a control low-fat diet (LFD) or a high-fat diet (HFD; 45% of calories from fat) and provided with running wheel access (LF-RUN or HF-RUN) or denied wheel access for our sedentary condition (LF-SED or HF-SED). The NLRP3 inflammasome-associated pathway, including NLRP3, caspase-1, and IL-1ß, in mice aorta was examined by RT-qPCR and FLICA and DAB staining. The protein expression of zonula occluden-1 (ZO-1), ZO-2, adiponectin (APN), and adiponectin receptor 1 (AdipoR1) in aortic endothelial cells was determined by immunofluorescence double staining. Intracellular reactive oxidative stress and nitric oxide (NO) production were monitored with fluorescence probes, dihydroethidium, and diaminofluorecein. RESULTS: HFD increased caspase-1 and IL-1ß at mRNA and protein levels in endothelial cells of the aorta, and this was attenuated by voluntary running. HFD decreased ZO-1 and ZO-2 expression and reduced APN and AdipoR1 signaling; these were restored by running. The elevated intracellular superoxide (O2) production observed in HF-SED was ameliorated in HF-RUN. Finally, HF-RUN improved NO production in the aorta compared with HF-SED. CONCLUSIONS: Our findings suggest that voluntary running ameliorates mechanisms associated with vascular dysfunction by suppressing NLRP3 inflammasome, improving NO production, and reducing oxidative stress. Such benefits of physical activity may be, at least in part, associated with APN-AdipoR1 signaling and tight junction protein expression.

High adenovirus 36 seroprevalence among a population of Hispanic American youth.

Infection with adenovirus 36 (Ad36) has been associated with risk of obesity in youth in some studies, but the seroprevalence of this virus has not been examined among all populations. As Hispanic-American youth are of greater risk for obesity than other American youth, we sought to determine the proportion of Ad36 seropositive (Ad36+) students in an urban middle school serving a Hispanic population. We further examined if Ad36+ students were more likely to have obesity, and if Ad36 serostatus impacted changes in weight status following a health intervention. We determined body mass index (BMI) at the beginning and end of a 16-week health intervention among 40 Hispanic-American middle-school students. Ad36 serostatus was determined by enzyme-linked immunsorbent assay (ELISA). Seventy percent of the students were Ad36+. Ad36+ and Ad36 seronegative (Ad36-) did not differ before or after the intervention in body weight measures. The odds of being classified as obese was 1.4 times greater among Ad36+ than Ad36- at baseline, and 2.4 times greater post-intervention, but these were not statistically significant. We report a high seroprevalence of Ad36 among a population of Hispanic-American students. Ad36 seropositivity was associated with a trend for a greater likelihood of having obesity, but did not impact response to a health intervention.