The effect of exercise intensity on the inflammatory profile of cancer survivors: A randomised crossover study.

BACKGROUND: Systemic inflammation has been clearly linked to poorer health outcomes from cancer diagnosis through to survivorship. There is accumulating evidence that exercise can reduce inflammation. However, the optimal intensity of exercise to reduce systemic inflammation is unknown. AIMS: The aim of this randomised crossover study was to identify the difference between high- and low-intensity aerobic exercise on the inflammatory profile of cancer survivors after a single exercise session (acute) and a short training period (six sessions over 2 weeks). METHOD: Participants (n = 20) were randomised to either low- or high-intensity exercise. They underwent 2 weeks of stationary cycling at their assigned intensity and then underwent a 6-week washout period of no exercise before returning to complete 2 weeks of exercise at the remaining intensity. RESULTS: Twenty participants with a mean age of 56.4 (±9.4) years were enrolled and completed the intervention. There was no effect of exercise intensity after a single exercise session. After 2 weeks of training, there was a significant effect of intensity on chemokines CCL2 (mean difference ± SEM; 13.2 pg/mL ± 5.0, p = .04) and CXCL12 (150.3 pg/mL ± 51.8, p = .02), where CCL2 was decreased after low-intensity exercise and CXCL12 decreased after high-intensity exercise. DISCUSSION: Our data suggest that while exercise intensity may impact different cell types in the circulation, both low- and high-intensity exercise can positively modulate inflammatory markers. CONCLUSION: The potential to scale up low-intensity exercise over time is likely to be more broadly applicable and achievable for cancer survivor cohorts while still eliciting beneficial effects on systemic inflammation.

Exercise testing and prescription in patients with inborn errors of muscle energy metabolism.

Skeletal muscle is a dynamic organ requiring tight regulation of energy metabolism in order to provide bursts of energy for effective function. Several inborn errors of muscle energy metabolism (IEMEM) affect skeletal muscle function and therefore the ability to initiate and sustain physical activity. Exercise testing can be valuable in supporting diagnosis, however its use remains limited due to the inconsistency in data to inform its application in IEMEM populations. While exercise testing is often used in adults with IEMEM, its use in children is far more limited. Once a physiological limitation has been identified and the aetiology defined, habitual exercise can assist with improving functional capacity, with reports supporting favourable adaptations in adult patients with IEMEM. Despite the potential benefits of structured exercise programs, data in paediatric populations remain limited. This review will focus on the utilisation and limitations of exercise testing and prescription for both adults and children, in the management of McArdle Disease, long chain fatty acid oxidation disorders, and primary mitochondrial myopathies.

Irradiation-Induced Dysbiosis: The Compounding Effect of High-Fat Diet on Metabolic and Immune Functions in Mice.

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.

Ballet after breast cancer: investigating the feasibility and acceptability of a novel 16-week classical ballet intervention for breast cancer survivors.

PURPOSE: The "Ballet after breast cancer" study sought to investigate the feasibility and acceptability of a 16-week classical ballet intervention for breast cancer survivors, delivered face-to-face and/or online. METHODS: Breast cancer survivors were recruited to take part in 2 × 1-h ballet classes per week for 16 weeks. Primary outcomes of feasibility and acceptability were assessed according to rates of enrolment and attendance and participant feedback via questionnaire. Secondary outcomes included quality of life (QOL), upper-body disability, shoulder range of motion (ROM), muscular strength, aerobic capacity, and physical activity levels. Associations between rate of attendance and changes in secondary measures were explored. RESULTS: Thirty-one participants (62% of eligible individuals) enrolled in the program. Twenty-nine women commenced the intervention [53.3 ± 10.8 years (Mean ± SD)], attending 77.6% [67.6, 87.5] (Mean [95% CI]) of sessions. Based on these rates of enrolment and attendance, and participant feedback, the program was deemed feasible and acceptable to participants. Significant improvements in shoulder ROM and reductions in sedentary behaviour were achieved. Participants also reported improvements in physical capacity and psychological, social, and cognitive wellbeing. CONCLUSIONS: The "Ballet after breast cancer" program, delivered face-to-face and/or online, was feasible and acceptable to breast cancer survivors. Improvements in shoulder ROM achieved doing ballet were pertinent given the adverse effects of upper-body morbidity on breast cancer survivor QOL. Improvements in physical activity behaviour and perceived benefits to wellbeing also support the use of ballet to mitigate QOL impairment after treatment. IMPLICATIONS FOR CANCER SURVIVORS: The physical demands and the fun, creative, and social characteristics of ballet promote improvement across multiple domains of health and wellbeing. Ballet shows promise as an activity to improve QOL and increase long-term engagement in health-promoting physical activity after breast cancer.

Parent perceptions of their child's and their own physical activity after treatment for childhood cancer.

PURPOSE: Parents are important facilitators of physical activity for children, yet little is known about the perceptions of parents of childhood cancer survivors. We investigated parent perceptions of their own and their child's physical activity levels after cancer treatment and examined associations with clinical, demographic, and psychosocial factors. METHODS: We conducted a cross-sectional survey among 125 parents and 125 survivors. Parents reported on the perceived importance of their child being physically active and concerns regarding exercising after cancer treatment. RESULTS: Parents and survivors self-reported median (range) of 127.5 (0-1260) and 220 (0-1470) min/week of moderate-to-vigorous physical activity. Most parents (n = 109, 98%) believed that physical activity was highly important for their child. Some parents (n = 19, 17%) reported concerns, most commonly regarding exercise safety (n = 7, 22%). Parents were more likely to perceive that their child should increase physical activity if their child was an adolescent and had high body fat percentage. CONCLUSIONS: Physical activity levels varied widely among survivors, reflecting factors including parents' lifestyles, limited understanding of exercise benefits and perceptions of risk. Given survivors' insufficient physical activity levels and sedentary behaviour among families, embedding physical activity promotion into health systems and follow-up support could benefit the entire family unit.

Accuracy of perceived physical activity and fitness levels among childhood cancer survivors.

BACKGROUND: Childhood cancer survivors do not engage in sufficient physical activity and have low fitness levels. Perceived physical activity and fitness levels may influence survivors' engagement in health behaviours. We aimed to investigate survivors' perceptions of physical activity and fitness levels and identify how accurate their perceptions were. We further explored survivors' attitudes toward physical activity, including perceived importance and desire to increase activity levels. PROCEDURE: We recruited 116 childhood cancer survivors (8-18 years) and assessed their perceived physical activity levels using a questionnaire and the Godin's Leisure Score Index. Accuracy of their perceptions was established by comparing their perceived physical activity levels with the recommended guidelines. Survivors reported their perceived fitness levels using the International Fitness Scale. We compared survivors' perceptions with their performance on the 6-minute walk test using weighted Cohen's kappa to determine interrater agreement between perceived and objectively measured fitness. RESULTS: Most survivors did not meet the physical activity guidelines (<420 min/week). One-third incorrectly perceived whether their self-reported physical activity levels were appropriate (84% underestimated, while 16% overestimated). Survivors had average fitness and were inaccurate at perceiving their fitness level. Survivors highly valued the importance of being able to do physical activity, and 89% reported a desire to increase their physical activity. CONCLUSIONS: Our results reveal that many survivors are not accurate when perceiving their physical activity and fitness levels. Emphasising the need for objective fitness assessments, and patient education in clinical practice may support survivors to accurately perceive their physical activity and fitness levels, thus improving health behaviours.

The 6-minute walk test is a good predictor of cardiorespiratory fitness in childhood cancer survivors when access to comprehensive testing is limited.

Cardiovascular disease is up to 10 times more likely among childhood cancer survivors compared to siblings. Low cardiorespiratory fitness is a modifiable risk-factor for cardiovascular diseases. Yet, cardiorespiratory fitness is not routinely screened in pediatric oncology, and healthy VO2max cut-points are unavailable. We aimed to predict cardiorespiratory fitness by developing a simple algorithm and establish cut-points identifying survivors' cardiovascular fitness health-risk zones. We recruited 262 childhood cancer survivors (8-18 years old, ≥1-year posttreatment). Participants completed gold-standard cardiorespiratory fitness assessment (Cardiopulmonary Exercise Test [CPET; VO2max ]) and 6-minute walk test (6MWT). Associations with VO2max were included in a linear regression algorithm to predict VO2max , which was then cross-validated. We used Bland-Altman's limits of agreement and Receiver Operating Characteristic curves using FITNESSGRAM's "Healthy Fitness Zones" to identify cut-points for adequate cardiorespiratory fitness. A total of 199 participants (aged 13.7 ± 2.7 years, 8.5 ± 3.5 years posttreatment) were included. We found a strong positive correlation between VO2max and 6MWT distance (r = 0.61, r2 = 0.37, p < 0.001). Our regression algorithm included 6MWT distance, waist-to-height ratio, age and sex to predict VO2max (r = 0.79, r2 = 0.62, p < 0.001). Forty percentages of predicted VO2max values were within ±3 ml/kg/min of measured VO2max . The cut-point for FITNESSGRAM's "health-risk" fitness zone was 39.8 ml/kg/min (males: AUC = 0.88), and 33.5 ml/kg/min (females: AUC = 0.82). We present an algorithm to reasonably predict cardiorespiratory fitness for childhood cancer survivors, using inexpensive measures. This algorithm has useful clinical application, particularly when CPET is unavailable. Our algorithm has the potential to assist clinicians to identify survivors below the cut-points with increased cardiovascular disease-risk, to monitor and refer for tailored interventions with exercise specialists.

Genes controlling the activation of natural killer lymphocytes are epigenetically remodeled in intestinal cells from germ-free mice.

Remodeling of the gut microbiota is implicated in various metabolic and inflammatory diseases of the gastrointestinal tract. We hypothesized that the gut microbiota affects the DNA methylation profile of intestinal epithelial cells (IECs) which could, in turn, alter intestinal function. In this study, we used mass spectrometry and methylated DNA capture to respectively investigate global and genome-wide DNA methylation of intestinal epithelial cells from germ-free (GF) and conventionally raised mice. In colonic IECs from GF mice, DNA was markedly hypermethylated. This was associated with a dramatic loss of ten-eleven-translocation activity, a lower DNA methyltransferase activity and lower circulating levels of the 1-carbon metabolite, folate. At the gene level, we found an enrichment for differentially methylated regions proximal to genes regulating the cytotoxicity of NK cells (false-discovery rate < 8.9E-6), notably genes regulating the cross-talk between NK cells and target cells, such as members of the NK group 2 member D ligand superfamily Raet. This distinct epigenetic signature was associated with a marked decrease in Raet1 expression and a loss of CD56+/CD45+ cells in the intestine of GF mice. Thus, our results indicate that altered activity of methylation-modifying enzymes in GF mice influences the IEC epigenome and modulates the crosstalk between IECs and NK cells. Epigenetic reprogramming of IECs may modulate intestinal function in diseases associated with altered gut microbiota.-Poupeau, A., Garde, C., Sulek, K., Citirikkaya, K., Treebak, J. T., Arumugam, M., Simar, D., Olofsson, L. E., Bäckhed, F., Barrès, R. Genes controlling the activation of natural killer lymphocytes are epigenetically remodeled in intestinal cells from germ-free mice.

Barriers and enablers to physical activity and aerobic fitness deficits among childhood cancer survivors.

BACKGROUND: Physical activity and aerobic fitness are modifiable risk factors for cardiovascular disease (CVD) after childhood cancer. How survivors engage in physical activity remains unclear, potentially increasing CVD risk. We assessed survivors' physical activity levels, barriers and enablers, fitness, and identified predictors of fitness and physical activity stage of change. METHODS: Childhood cancer survivors (CCS; 8-18 years old) ≥1 year post-treatment were assessed for aerobic fitness (6-min walk test), used to extrapolate VO2max , and body composition (InBody 570). Survivors self-reported physical activity to determine stage of change (Patient-Centered Assessment and Counselling for Exercise). Physical activity and fitness were compared with guidelines and CVD-risk cut-points (VO2max  < 42 mL/kg/min: males; VO2max  < 35 mL/kg/min: females). Multiple regression and mediator-moderator analysis were used to identify fitness predictors and stage of change. RESULTS: One hundred two survivors (12.8 ± 3.3 years) participated (46% acute lymphoblastic leukaemia). Forty percent of males (VO2max  = 43.3 ± 6.3 mL/kg/min) and 28% of females (VO2max  = 36.5 ± 5.9 mL/kg/min) were in the CVD-risk category, while 25% met physical activity guidelines. Most prevalent physical activity barriers were fatigue (52%), preferring television instead of exercise (38%), and lacking time (34%). Predictive factors for reduced fitness included being older, female, higher waist-to-height ratio, higher screen time, and moderated by lower physical activity (r2  = 0.91, P < .001). Survivors with higher physical activity stage of change were male, lower body fat percentage, lower screen time, and lived with both parents (r = 0.42, P = .003). CONCLUSION: Aerobic fitness and physical activity of CCS is low compared with population norms, potentially increasing CVD risk. Addressing physical activity barriers and enablers, including reducing screen time, could promote regular physical activity, reducing CVD risk.

Preadipocytes from obese humans with type 2 diabetes are epigenetically reprogrammed at genes controlling adipose tissue function.

BACKGROUND: Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function of preadipocytes. METHODS: The transcriptomic profile of visceral adipose tissue preadipocytes collected from Lean, Obese and Obese with T2D was assessed throughout in vitro differentiation using RNA sequencing. Reduced Representation Bisulfite Sequencing was used to establish the genome-wide DNA methylation profile of human preadipocytes and 3T3-L1 preadipocytes treated by the inflammatory cytokine Tumour Necrosis Factor-α (TNF-α) or palmitate. RESULTS: While preadipocytes from all obese subjects (Obese+Obese T2D), compared to those of Lean, were transcriptionally different in response to differentiation in culture, preadipocytes from Obese T2D showed impaired insulin signalling and a further transcriptomic shift towards altered adipocyte function. Cultures with a lower expression magnitude of adipogenic genes throughout differentiation (PLIN1, CIDEC, FABP4, ADIPOQ, LPL, PDK4, APOE, LIPE, FABP3, LEP, RBP4 and CD36) were associated with DNA methylation remodelling at genes controlling insulin sensitivity and adipocytokine signalling pathways. Prior incubation of 3T3-L1 preadipocytes with TNF-α or palmitate markedly altered insulin responsiveness and metabolic function in the differentiated adipocytes, and remodelled DNA methylation and gene expression at specific genes, notably related to PPAR signalling. CONCLUSIONS: Our findings that preadipocytes retain the memory of the donor in culture and can be reprogrammed by extracellular factors support a mechanism by which adipocyte precursors are epigenetically reprogrammed in vivo. Epigenetic reprogramming of preadipocytes represents a mechanism by which metabolic function of visceral adipose tissue may be affected in the long term by past exposure to obesity- or T2D-specific factors.

Barriers and facilitators of exercise experienced by cancer survivors: a mixed methods systematic review.

PURPOSE: Exercise 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. METHOD: MEDLINE, 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. RESULTS: Nineteen 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. CONCLUSION: Treatment-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.

Characterisation of the cytokine milieu associated with the up-regulation of IL-6 and suppressor of cytokine 3 in chronic hepatitis C treatment non-responders.

BACKGROUND & AIMS: In chronic hepatitis C virus infection (CHC), expression of suppressor of cytokine signalling-3 (SOCS3) has been shown to be associated with obesity and non-response to antiviral therapy. In this study, we aimed to determine the effect of SOCS3 induction on the cytokine response in patients receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy. METHODS: Peripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein SOCS3 expression. Immunological assays were employed to examine cytokine production. RESULTS: There was increased expression of SOCS3 in PBMC of non-responders at week 12 of therapy, when compared to treatment responders (P = 0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r = 0.54; P = 0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV-specific IFN-γ production in enzyme-linked immunosorbent spot (ELISpot) assays (P = 0.01), and reduced ex-vivo production of the anti-HCV effector cytokines interleukin (IL)-2 and tumour necrosis factor (TNF)-α(P = 0.01 and P = 0.04 respectively). Analysis of serum cytokine levels revealed higher levels of IL-6 at week 12 in the high SOCS3 expression group (P = 0.02) while IL-6 levels correlated with SOCS3 expression in the entire cohort (P = 0.04). Ex-vivo studies confirmed that IL-6 induced SOCS3, and neutralisation of IL-6 reduced levels of SOCS3. CONCLUSION: In subjects with increased BMI and non-response to antiviral therapy, the IL-6/SOCS3 axis appears to play a crucial role in altering the anti-HCV-cytokine response associated with antiviral therapy.

Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents.

AIMS/HYPOTHESIS: Maternal obesity leads to increased adiposity, hyperlipidaemia and glucose intolerance in offspring. The analogue of glucagon-like peptide-1, exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce body fat and improve metabolic disorders in offspring from obese dams, especially those consuming a high-fat diet (HFD). METHODS: Female Sprague Dawley rats were fed chow or an HFD for 5 weeks before mating, and throughout gestation and lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto chow or HFD and those from chow-fed mothers were fed chow. Within each dietary group, half of the pups were injected with Ex-4 (15 µg/kg/day i.p.) for 6 weeks, while the other half received saline. RESULTS: Maternal obesity alone or combined with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia, hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite regulators by glucose in offspring, while glucose intolerance was only observed in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity, hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also restored glucose tolerance and the lipid-lowering effect of blood glucose. However, Ex-4 did not change hypothalamic appetite regulation or the response of appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine expression was significantly reduced by Ex-4. CONCLUSIONS/INTERPRETATION: Ex-4 reversed the detrimental impact of maternal obesity on lipid and glucose metabolism in offspring regardless of diet, supporting its potential application in reducing metabolic disorders in high-risk populations.

Maternal obesity impairs brain glucose metabolism and neural response to hyperglycemia in male rat offspring.

Hypothalamic appetite regulators neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) are modulated by glucose. This study investigated how maternal obesity disturbs glucose regulation of NPY and POMC, and whether this deregulation is linked to abnormal hypothalamic glucose uptake-lactate conversion. As post-natal high-fat diet (HFD) can exaggerate the effects of maternal obesity, its additional impact was also investigated. Female Sprague Dawley rats were fed a HFD (20 kJ/g) to model maternal obesity. At weaning, male pups were fed chow or HFD. At 9 weeks, in vivo hypothalamic NPY and POMC mRNA responses to acute hyperglycemia were measured; while hypothalami were glucose challenged in vitro to assess glucose uptake-lactate release and related gene expression. Maternal obesity dampened in vivo hypothalamic NPY response to acute hyperglycemia, and lowered in vitro hypothalamic glucose uptake and lactate release. When challenged with 20 mM glucose, hypothalamic glucose transporter 1, monocarboxylate transporters, lactate dehydrogenase-b, NPY and POMC mRNA expression were down-regulated in offspring exposed to maternal obesity. Post-natal HFD consumption reduced in vitro lactate release and monocarboxylate transporter 2 mRNA, but increased POMC mRNA levels when challenged with 20 mM glucose. Overall, maternal obesity produced stronger effects than post-natal HFD consumption to impair hypothalamic glucose metabolism. However, they both disturbed NPY response to hyperglycemia, potentially leading to hyperphagia.

Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness.

We investigated the effect of exercise in the heat on both intracellular and extracellular Hsp72 in athletes with a prior history of exertional heat illness (EHI). Two groups of runners, one consisting of athletes who had a previous history of EHI, and a control group (CON) of similar age (29.7 ± 1.2 and 29.1 ± 2 years CON vs. EHI) and fitness [maximal oxygen consumption [Formula: see text] 65.7 ± 2 and 64.5 ± 3 ml kg(-1) min(-1) CON vs. EHI] were recruited. Seven subjects in each group ran on a treadmill for 1 h at 72 % [Formula: see text] in warm conditions (30 °C, 40 % RH) reaching rectal temperatures of ~39.3 (CON) and ~39.2 °C (EHI). Blood was collected every 10 min during exercise and plasma was analysed for extracellular Hsp72. Intracellular Hsp72 levels were measured in both monocytes and lymphocytes before and immediately after the 60-min run, and then after 1 h recovery at an ambient temperature of 24 °C. Plasma Hsp72 increased from 1.18 ± 0.14 and 0.86 ± 0.08 ng/ml (CON vs. EHI) at rest to 4.56 ± 0.63 and 4.04 ± 0.45 ng/ml (CON vs. EHI, respectively) at the end of exercise (p < 0.001), with no difference between groups. Lymphocyte Hsp72 was lower in the EHI group at 60 min of exercise (p < 0.05), while monocyte Hsp72 was not different between groups. The results of the present study suggest that the plasma Hsp72 response to exercise in athletes with a prior history of EHI remained similar to that of the CON group, while the lymphocyte Hsp72 response was reduced.

Patterns of physical activity and sedentary behavior in child and adolescent cancer survivors assessed using wrist accelerometry: A cluster analysis approach.

Physical activity levels among childhood cancer survivors are typically quantified as a total amount using time spent in various intensities. Yet, most analyses do not consider the transitory nature of children's behaviors and a more detailed approach could provide complimentary information. We aimed to explore various behavior profiles of survivors' daily and hourly physical activity patterns. We measured 8-18-year-old survivors' activity levels over 7 days using wrist accelerometry and cluster analysis. Of the 37 participant datasets, survivors engaged in mean (SD) 36.3 (19.0) min/day of MVPA and 4.1 (1.9) hrs/day of sedentary activity. The cluster analysis revealed five daily movement patterns: 'most active' (prevalence 11%), 'active' (22%), 'moderately active + moderately sedentary' (35%), 'moderately active + high sedentary' (5%) and 'least active' (27%). Younger survivors and those with less time since treatment completion were more likely to be in the active clusters. Hourly behaviors were characterized by short bursts of MVPA and moderate bouts of sedentary activity. Our approach provides an insightful analysis into the nature and timing of childhood cancer survivors' movement behaviours. Our findings may assist in the development of targeted interventions to improve physical activity levels.

Evaluating the effect of upper-body morbidity on quality of life following primary breast cancer treatment: a systematic review and meta-analysis.

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.

A Digital Educational Intervention With Wearable Activity Trackers to Support Health Behaviors Among Childhood Cancer Survivors: Pilot Feasibility and Acceptability Study.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000259842; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12621000259842.

Effect of High-Intensity Power Training on Cognitive Function in Older Adults With Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Study.

We sought to determine the effects of 12 months of power training on cognition, and whether improvements in body composition, muscle strength, and/or aerobic capacity (VO2peak) were associated with improvements in cognition in older adults with type 2 diabetes (T2D). Participants with T2D were randomized to power training or low-intensity sham exercise control condition, 3 days per week for 12 months. Cognitive outcomes included memory, attention/speed, executive function, and global cognition. Other relevant outcomes included VO2peak, strength, and whole body and regional body composition. One hundred and three adults with T2D (mean age 67.9 years; standard deviation [SD] 5.9; 50.5% women) were enrolled and analyzed. Unexpectedly, there was a nearly significant improvement in global cognition (p = .05) in the sham group relative to power training, although both groups improved over time (p < .01). There were significant interactions between group allocation and body composition or muscle strength in the models predicting cognitive changes. Therefore, after stratifying by group allocation, improvements in immediate memory were associated with increases in relative skeletal muscle mass (r = 0.38, p = .03), reductions in relative body fat (r = -0.40, p = .02), and increases in knee extension strength were directly related to changes in executive function (r = -0.41, p = .02) within the power training group. None of these relationships were present in the sham group (p > .05). Although power training did not significantly improve cognition compared to low-intensity exercise control, improvements in cognitive function in older adults were associated with hypothesized improvements in body composition and strength after power training.

The effect of exercise intensity on exercise-induced hypoalgesia in cancer survivors: A randomized crossover trial.

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.