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PurposeExercise has been shown to improve the health and well-being of people who have survived cancer. Yet, less than 40% of cancer survivors in Australia meet the recommended 150 min of moderate-intensity physical activity per week. Our objective was to systematically review the literature regarding barriers, facilitators and preferences for exercise for survivors of cancer.MethodMEDLINE, EMBASE, CINAHL, PsycINFO and Scopus were searched for qualitative and quantitative articles addressing barriers, facilitators and preferences for exercise in cancer survivors. Quality assessment was performed by two independent reviewers using the Mixed Methods Appraisal Tool. Thomas and Harden’s method of thematic synthesis was used to amalgamate qualitative data while descriptive statistics were used to collate quantitative data.ResultsNineteen studies were included (9 qualitative and 10 quantitative). Persisting treatment-related side effects was the most commonly reported barrier to initiating or maintaining exercise, followed by lack of time and fatigue. The most common facilitators of exercise were gaining a feeling of control over their health as well as managing emotions and mental well-being, while the preferred method of exercise was walking. We also identified a lack of useful information provided to survivors regarding exercise.ConclusionTreatment-related side effects, lack of time and fatigue were key barriers to exercise for survivors of varied cancer types. Insufficient patient education may contribute to the belief that exercise is not helpful when experiencing side effects of treatment, including fatigue. Identifying barriers and facilitators leads to improved support and education from health professionals which is required to provide safe and effective exercise recommendations for survivors.

Introduction Patients with McArdle disease have reduced exercise capacity. Structured exercise programs in adults with McArdle disease can improve aerobic capacity and strength. However, structured exercise has not been evaluated in younger populations. Our aim was to determine the safety, feasibility, and acceptability of an exercise intervention in children and young adults with McArdle disease. Methods Children and young adults aged 5–30 years with McArdle disease were recruited through metabolic clinics in New South Wales, Australia, to complete a remote, supervised 12-week exercise intervention. Pre and/or post intervention, participants completed a treadmill cardiopulmonary exercise test (CPET), strength testing, habitual physical activity monitoring, a quality-of-life questionnaire, acceptability questionnaire, muscular Near Infrared Spectroscopy (NIRS), and blood samples. Results Five out of 10 eligible participants, with a median age of 17 years (range 13–29), were enrolled. Four met the feasibility target of 70% completed exercise sessions. Four episodes of mild rhabdomyolysis were reported during the study, but no participant required hospital admission. All participants reported they would participate in similar programs in the future. No significant changes were found in aerobic capacity, strength, habitual physical activity levels or quality of life. Trends were observed for lower perceived pain during CPET, and improved leg press. NIRS indicated a possible trend for improved muscle oxygen utilisation. Conclusion A 12-week remotely delivered exercise intervention was found to be feasible, safe, and acceptable to children and young adults with McArdle disease. Although improvements to aerobic capacity and strength were not elicited, individual clinical benefits may have occurred. One sentence take home message An exercise intervention in children and young adults with McArdle disease is feasible, safe, and acceptable, and may elicit individual clinical benefits.

Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear. Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control). At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid) metabolic markers were measured. Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain. Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanism. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.

Purpose Improvements in breast cancer management continue to increase survival and life expectancy after treatment. Yet the adverse effects of treatment may persist long term, threatening physical, psychological, and social wellbeing, leading to impaired quality of life (QOL). Upper-body morbidity (UBM) such as pain, lymphoedema, restricted shoulder range of motion (ROM), and impaired function are widely reported after breast cancer treatment, but evidence demonstrating its impact on QOL is inconsistent. Therefore, the aim of the study was to conduct a systematic review and meta-analysis evaluating the effect of UBM on QOL following primary breast cancer treatment. Methods The study was prospectively registered on PROSPERO (CRD42020203445). CINAHL, Embase, Emcare, PsycInfo, PubMed/Medline, and SPORTDiscus databases were searched for studies reporting QOL in individuals with and without UBM following primary breast cancer treatment. Primary analysis determined the standardised mean difference (SMD) in physical, psychological, and social wellbeing scores between UBM + /UBM − groups. Secondary analyses identified differences in QOL scores between groups, according to questionnaire. Results Fifty-eight studies were included, with 39 conducive to meta-analysis. Types of UBM included pain, lymphoedema, restricted shoulder ROM, impaired upper-body function, and upper-body symptoms. UBM + groups reported poorer physical (SMD =  − 0.99; 95%CI =  − 1.26, − 0.71; p  < 0.00001), psychological (SMD =  − 0.43; 95%CI =  − 0.60, − 0.27; p  < 0.00001), and social wellbeing (SMD =  − 0.62; 95%CI =  − 0.83, − 0.40; p  < 0.00001) than UBM − groups. Secondary analyses according to questionnaire showed that UBM + groups rated their QOL poorer or at equal to, UBM − groups across all domains. Conclusions Findings demonstrate the significant, negative impact of UBM on QOL, pervading physical, psychological, and social domains. Implications for Cancer Survivors Efforts to assess and minimise the multidimensional impact of UBM are warranted to mitigate impaired QOL after breast cancer.

To determine the genomic mechanisms by which adipose tissue responds to acute and chronic exercise. We profiled the transcriptomic and epigenetic response to acute exercise in human adipose tissue collected before and after endurance training. Although acute exercises were performed at same relative intensities, the magnitude of transcriptomic changes after acute exercise was reduced by endurance training. DNA methylation remodeling induced by acute exercise was more prominent in trained versus untrained state. We found an overlap between gene expression and DNA methylation changes after acute exercise for 32 genes pre-training and six post-training, notably at adipocyte-specific genes. Training status differentially affects the epigenetic and transcriptomic response to acute exercise in human adipose tissue.

The negative impact of irradiation or diet on the metabolic and immune profiles of cancer survivors have been previously demonstrated. The gut microbiota plays a critical role in regulating these functions and is highly sensitive to cancer therapies. The aim of this study was to investigate the effect of irradiation and diet on the gut microbiota and metabolic or immune functions. We exposed C57Bl/6J mice to a single dose of 6 Gy radiation and after 5 weeks, fed them a chow or high-fat diet (HFD) for 12 weeks. We characterised their faecal microbiota, metabolic (whole body and adipose tissue) functions, and systemic (multiplex cytokine, chemokine assay, and immune cell profiling) and adipose tissue inflammatory profiles (immune cell profiling). At the end of the study, we observed a compounding effect of irradiation and diet on the metabolic and immune profiles of adipose tissue, with exposed mice fed a HFD displaying a greater inflammatory signature and impaired metabolism. Mice fed a HFD also showed altered microbiota, irrespective of irradiation status. An altered diet may exacerbate the detrimental effects of irradiation on both the metabolic and inflammatory profiles. This could have implications for the diagnosis and prevention of metabolic complications in cancer survivors exposed to radiation.

Childhood cancer survivors are at increased risk of cardiometabolic complications that are exacerbated by poor health behaviors. Critically, many survivors do not meet physical activity guidelines. The primary aim was to evaluate the feasibility and acceptability of iBounce, a digital health intervention for educating and engaging survivors in physical activity. Our secondary aims were to assess the change in survivors' physical activity levels and behaviors, aerobic fitness, and health-related quality of life (HRQoL) after participating in the iBounce program. We recruited survivors aged 8 to 13 years who were ≥12 months post cancer treatment completion. The app-based program involved 10 educational modules, goal setting, and home-based physical activities monitored using an activity tracker. We assessed objective physical activity levels and behaviors using cluster analysis, aerobic fitness, and HRQoL at baseline and after the intervention (week 12). Parents were trained to reassess aerobic fitness at home at follow-up (week 24). In total, 30 participants opted in, of whom 27 (90%) completed baseline assessments, and 23 (77%) commenced iBounce. Our opt-in rate was 59% (30/51), and most (19/23, 83%) of the survivors completed the intervention. More than half (13/23, 57%) of the survivors completed all 10 modules (median 10, IQR 4-10). We achieved a high retention rate (19/27, 70%) and activity tracker compliance (15/19, 79%), and there were no intervention-related adverse events. Survivors reported high satisfaction with iBounce (median enjoyment score 75%; ease-of-use score 86%), but lower satisfaction with the activity tracker (median enjoyment score 60%). Parents reported the program activities to be acceptable (median score 70%), and their overall satisfaction was 60%, potentially because of technological difficulties that resulted in the program becoming disjointed. We did not observe any significant changes in physical activity levels or HRQoL at week 12. Our subgroup analysis for changes in physical activity behaviors in participants (n=11) revealed five cluster groups: most active, active, moderately active, occasionally active, and least active. Of these 11 survivors, 3 (27%) moved to a more active cluster group, highlighting their engagement in more frequent and sustained bouts of moderate-to-vigorous physical activity; 6 (56%) stayed in the same cluster; and 2 (18%) moved to a less active cluster. The survivors' mean aerobic fitness percentiles increased after completing iBounce (change +17, 95% CI 1.7-32.1; P=.03) but not at follow-up (P=.39). We demonstrated iBounce to be feasible for delivery and acceptable among survivors, despite some technical difficulties. The distance-delivered format provides an opportunity to engage survivors in physical activity at home and may address barriers to care, particularly for regional or remote families. We will use these pilot findings to evaluate an updated version of iBounce. Australian New Zealand Clinical Trials Registry ACTRN12621000259842; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12621000259842.

Background Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory diseases in cancer survivors. Results To test this hypothesis, we established the epigenetic and transcriptomic profiles of immune cells from 44 childhood cancer survivors (CCS, > 16 years old) on full remission (> 5 years) who had received chemotherapy alone or in combination with total body irradiation (TBI) and hematopoietic stem cell transplant (HSCT). We found that more than 10 years post-treatment, CCS treated with TBI/HSCT showed an altered DNA methylation signature in T cell, particularly at genes controlling immune and inflammatory processes and oxidative stress. DNA methylation remodeling in T cell was partially associated with chronic expression changes of nearby genes, increased frequency of type 1 cytokine-producing T cell, elevated systemic levels of these cytokines, and over-activation of related signaling pathways. Survivors exposed to TBI/HSCT were further characterized by an Epigenetic-Aging-Signature of T cell consistent with accelerated epigenetic aging. To investigate the potential contribution of irradiation to these changes, we established two cell culture models. We identified that radiation partially recapitulated the immune changes observed in survivors through a bystander effect that could be mediated by circulating factors. Conclusion Cancer treatments, in particular TBI/HSCT, are associated with long-term immune disturbances. We propose that epigenetic remodeling of immune cells following cancer therapy augments inflammatory- and age-related diseases, including metabolic complications, in childhood cancer survivors.

Abstract The role of exercise-induced oxidative stress in the reduced quadriceps endurance of chronic obstructive pulmonary disease (COPD) patients has never been shown. We conducted a randomized, double-blind, and crossover study in which nine severe patients performed localized dynamic quadriceps endurance tests at 40% of maximal strength after oral treatment with the antioxidant, N-acetylcysteine (NAC), and placebo. Venous blood was sampled before, immediately after exercise, and 6 hours later. Endurance time improved by 25% after NAC treatment compared with placebo (p < 0.05). Superoxide anion (oxidant) release by stimulated phagocytes decreased after treatment (p < 0.05). No change in the antioxidant system was observed. Lipid peroxidation, an index of oxidative stress, was significantly increased 6 hours after exercise in the placebo condition (p < 0.05) but not after treatment. Advanced oxidized protein products, another index of oxidative stress, were also increased 6 hours after exercise by 139 ± 27% in the placebo condition but only by 54 ± 19% after treatment (p < 0.05). This study shows that NAC treatment in COPD reduced basal disturbance in the prooxidant system, improved endurance time, and prevented exercise-induced oxidative stress. Oxidative stress thus seems to be implicated in the reduced quadriceps endurance of patients with COPD.

Pain is experienced by people with cancer during treatment and in survivorship. Exercise can have an acute hypoalgesic effect (exercise‐induced hypoalgesia; EIH) in healthy individuals and some chronic pain states. However, EIH, and the moderating effect of exercise intensity, has not been investigated in cancer survivors. This study examined the effect of low‐ and high‐intensity aerobic exercise on EIH in cancer survivors after a single exercise session as well as a brief period of exercise training (2‐weeks, three exercise sessions per week). Participants (N = 19) were randomized to low‐ (30%–40% Heart Rate Reserve (HRR) or high‐ (60%–70% HRR) intensity stationary cycling for 15–20 min. Pressure pain thresholds (PPT) were assessed over the rectus femoris and biceps brachii before and after a single exercise session and again after a short training period at the assigned intensity. Then, following a 6‐week washout period, the intervention was repeated at the other intensity. After the first exercise session, high‐intensity exercise resulted in greater EIH over the rectus femoris than low intensity (mean difference ± SE: −0.51 kg/cm2 ± 0.15, Cohen's d = 0.78, p = 0.004). After a 2‐week training period, we found no difference in EIH between intensities (0.01 kg/cm2 ± 0.25, d = 0.00 p = 0.99), with comparable moderate effect sizes for both low‐ and high‐intensity exercise, indicative of EIH. No EIH was observed over the biceps brachii of the arm at either low or high intensity. Low‐intensity exercise training may be a feasible option to increase pain thresholds in cancer survivors. High‐intensity exercise increased pressure pain thresholds more than low‐intensity exercise over the exercising muscle of the leg. However, after a short training period, there was no difference between low‐ and high‐intensity exercise on pain thresholds, with both intensities eliciting a hypoalgesic effect. These results suggest that both low‐ and high‐intensity exercise training may be effective at increasing pain thresholds in cancer survivors.