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).

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.

Human cytomegalovirus infection and the immune response to exercise.

Human cytomegalovirus (HCMV) is a ubiquitous -herpes virus that has co-evolved with its host since the very beginning of human life. The vast majority of adults worldwide carry the virus in a latent state, which is known to have striking effects on the composition and function of both T-cells and NK-cells. While there is evidence to suggest that prior exposure to HCMV can have beneficial effects in the immune competent host, poor control of the virus may contribute to T-cell exhaustion and the early onset of immunosenescence. The interaction between HCMV and exercise has garnered a lot of recent research attention. This stemmed from observations that people with HCMV redeploy greater numbers of CD8+ T-cells in response to a single exercise bout, while NK-cell mobilization is, conversely, impaired. Moreover, athletes with latent HCMV infection may be better protected against symptoms of upper respiratory illness (URI), and it has been suggested that the host's ability to control HCMV (i.e. keeping CMV in a latent state) may connect apparent bidirectional effects of exercise volume on host immunity and infection risk. This work has set a new paradigm that immune responses to both acute and chronic exercise might be governed by the infection history of the host. In this review, we summarize current knowledge on the effects of HCMV infection on T-cells and NK-cells and synthesize the literature on HCMV and the immune response to both single exercise bouts and prolonged periods of exercise training. We also discuss potential clinical and practical applications of this work including the use of HCMV reactivation as a biomarker of immune depression in athletes, its relevance in immunosenescence and the associated immune risk profile, and the potential for exercise to augment vaccine responses and the man ufacture of immune cells for adoptive transfer immunotherapy. Although research in this area is still in its infancy, we conclude that host infection history and the ability to regulate dormant pathogens is likely to play a key role in our understanding of how the immune system responds to both acute and chronic exercise across the entire exercise volume continuum.

Exercise, inflammation, and fatigue in cancer survivors.

Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue.

A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults.

The ex vivo expansion of tumor-associated-antigen (TAA)- specific cytotoxic T-cells (CTLs) from healthy donors for adoptive transfer to cancer patients is now providing additional treatment options for patients. Many studies have shown that adoptive transfer of expanded CTLs can reduce the risk of relapse in cancer patients following hematopoietic stem cell transplantation (HSCT). However, the procedure can be limited by difficulties in priming and expanding sufficient numbers of TAA-specific-CTLs. Because acute dynamic exercise mobilizes large numbers of T-cells to peripheral blood, we hypothesized that a single bout of exercise would augment the ex vivo expansion of TAA-specific-CTLs.We therefore collected lymphocytes from blood donated by healthy adults at rest and after brief maximal dynamic exercise. TAA-specific CTLs were expanded using autologous monocyte-derived-dendritic cells pulsed with melanoma-associated antigen 4 (MAGE-A4), with preferentially expressed antigen in melanoma (PRAME), and with Wilms' tumor protein (WT-1). Post exercise, 84% of the participants had a greater number of CTLs specific for at least one of the three TAA.Cells expanded from post exercise blood yielded a greater number of MAGE-A4 and PRAME-specific-cells in 70% and 61% of participants, respectively. In the 'exercise-responsive' participants (defined as participants with at least a 10% increase in TAA-specific-CTLs post-exercise), MAGEA4- and PRAME-specific-CTLs increased 3.4-fold and 6.2- fold respectively. Moreover, expanded TAA-specific CTLs retained their antigen-specific cytotoxic activity. No phenotype differences were observed between expanded cells donated at rest and postexercise. We conclude that exercise can enhance the ex vivo expansion of TAA-specific-CTLs from healthy adults without compromising cytotoxic function. Hence, this study has implications for immunotherapy using adoptive T-cell transfer of donor-derived T-cells after allogeneic HSCT.

A single bout of dynamic exercise by healthy adults enhances the generation of monocyte-derived-dendritic cells.

The ex vivo generation of monocyte-derived-dendritic cells (mo-DCs) has facilitated the use of DCs in immunotherapy research. However, low blood monocyte numbers frequently limit the manufacture of sufficient numbers of mo-DCs for subsequent experimental and clinical procedures. Because exercise mobilizes monocytes to the blood, we tested if acute dynamic exercise by healthy adults would augment the generation of mo-DCs without compromising their differentiation or function. We compared mo-DC generation from before- and after-exercise blood over 8-days of culture. Function was assessed by FITC-dextran uptake and the stimulation of autologous cytomegalovirus (pp65)-specific-T-cells. Supporting the hypothesis, we found a near fourfold increase in number of mo-DCs generated after-exercise. Furthermore, relative FITC-dextran uptake, differentiation rate, and stimulation of pp65-specific-T-cells did not differ between before- and after-exercise mo-DCs. We conclude that exercise enhances the ex vivo generation of mo-DCs without compromising their function, and so may overcome some limitations associated with manufacturing these cells for immunotherapy.

The effects of age and latent cytomegalovirus infection on the redeployment of CD8+ T cell subsets in response to acute exercise in humans.

Dynamic exercise evokes a rapid redeployment of cytotoxic T cell subsets with high expression of ß2 adrenergic receptors, presumably to enhance immunosurveillance during acute stress. As this response is affected by age and infection history, this study examined latent CMV infection as a potential confounder to age-related differences in blood CD8+ T-cell responses to exercise. Healthy young (n=16) and older (n=16) humans counterbalanced by CMV IgG serostatus (positive or negative) exercised for 30-min at ∼80% peak cycling power. Those with CMV redeployed ∼2-times more CD8+ T-cells and ∼6-times more KLRG1+/CD28- and CD45RA+/CCR7- CD8+ subsets than non-infected exercisers. Seronegative older exercisers had an impaired redeployment of total CD8+ T-cells, CD45RA+/CCR7+ and KLRG1-/CD28+ CD8+ subsets compared to young. Redeployed CD8+ T-cell numbers were similar between infected young and old. CMVpp65 specific CD8+ cells in HLA/A2(∗) subjects increased ∼2.7-fold after exercise, a response that was driven by the KLRG1+/CD28-/CD8+ subset. Stimulating PBMCs before and after exercise with CMVpp65 and CMV IE-1 antigens and overlapping peptide pools revealed a 2.1 and 4.4-fold increases in CMVpp65 and CMV IE-1 IFN-γ secreting cells respectively. The breadth of the T cell response was maintained after exercise with the magnitude of the response being amplified across the entire epitope repertoire. To conclude, latent CMV infection overrides age-related impairments in CD8+ T-cell redeployment with exercise. We also show for the first time that many T-cells redeployed with exercise are specific to CMVpp65 and CMV IE-1 antigens, have broad epitope specificity, and are mostly of a high-differentiated effector memory phenotype.

Latent cytomegalovirus infection and innate immune function following a 75 km cycling time trial.

PURPOSE: This study compared the acute immune response, inflammation, and lipid peroxidation to a 75 km cycling time trial in male athletes testing positive or negative for latent cytomegalovirus (CMV) infection. DESIGN: Trained cyclists (N = 20) were tested for CMV serostatus, and cycled 75 km on a mountainous course using indoor trainers with continuous workload monitoring. Pre-, post-, and 1 h post-exercise blood samples were analyzed for total blood leukocyte counts, blood granulocyte (GR) and monocyte (MO) phagocytosis (PHAG) and oxidative burst activity (OBA), four plasma cytokines, and plasma F2-isoprostanes. RESULTS: Forty percent of the subjects tested positive for CMV. No differences in subject characteristics were found between CMVpos and CMVneg groups. Mean power (57.3 ± 1.6, 59.4 ± 1.8 % maximal Watts, p = 0.803), heart rate (87.0 ± 1.0, 86.5 ± 1.3 % maximal heart rate, p = 0.376), and total time (2.56 ± 0.08, 2.60 ± 0.08 h, p = 0.744) to complete the 75 km cycling time trial did not differ between CMVpos and CMVneg groups. Whereas exercise induced significant changes in total blood leukocyte counts, GR and MO-PHAG, four plasma cytokines, and plasma F2-isoprostanes (p < 0.05, ω(2) > 0.03), these exercise-induced changes did not differ between CMVpos and CMVneg groups (p > 0.05, ω(2) < 0.01). CONCLUSIONS: CMV serostatus does not appear to influence these innate immune responses or markers of inflammation and lipid peroxidation in response to a single bout of heavy exertion.

Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?

Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients.

Immune responses to exercising in a cold environment.

Cold temperature and exercise independently impose stress on the human body that can lead to circulatory and metabolic changes, and depress the immune system. Multiple stressors applied together may amplify this immunodepression, causing greater immune impairment and heightened infection risk than with either stressor alone. As such, winter athletes and other persons who work or physically exert themselves in cold temperatures may have greater levels of stress-induced immune impairment than would be expected under mild temperatures. This review examines the literature regarding changes to physiological and immunological parameters arising from exposure to cold temperatures and to exercise. Even brief exposure to cold leads to increased levels of norepinephrine and cortisol, lymphocytosis, decreased lymphoproliferative responses, decreased levels of TH1 cytokines and salivary IgA, and increased lactate levels during exercise. Whether these changes lead to increased susceptibility to infection, as suggested by some epidemiological reports, remains to be determined. Although there is some evidence that exercising in temperatures near 5°C leads to greater immune impairment compared to exercising in milder temperatures, there is a need to explore the effects of exercise on immunity in the subfreezing conditions typically encountered by winter athletes. This is required to fully determine the extent to which performing vigorous exercise in subfreezing temperatures amplifies exercise-induced immune impairment and infection risk.