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Background: Blood pressure (BP) is an important modifiable cardiovascular risk factor, yet its long-term monitoring remains problematic. Wearable cuffless devices enable the capture of multiple BP measures during everyday activities and could improve BP monitoring, but little is known about their validity or acceptability., Objective: This study aimed to validate a wrist-worn cuffless wearable BP device (Model T2; TMART Technologies Limited) and assess its acceptability among users and health care professionals., Methods: A mixed methods study was conducted to examine the validity and comparability of a wearable cuffless BP device against ambulatory and home devices. BP was measured simultaneously over 24 hours using wearable and ambulatory devices and over 7 days using wearable and home devices. Pearson correlation coefficients compared the degree of association between the measures, and limits of agreement (LOA; Bland-Altman plots) were generated to assess measurement bias. Semistructured interviews were conducted with users and 10 health care professionals to assess acceptability, facilitators, and barriers to using the wearable device. Interviews were audio recorded, transcribed, and analyzed., Results: A total of 9090 BP measurements were collected from 20 healthy volunteers (mean 20.3 years, SD 5.4; N=10 females). Mean (SD) systolic BP (SBP)/diastolic BP (DBP) measured using the ambulatory (24 hours), home (7 days), and wearable (7 days) devices were 126 (SD 10)/75 (SD 6) mm Hg, 112 (SD 10)/71 (SD 9) mm Hg and 125 (SD 4)/77 (SD 3) mm Hg, respectively. Mean (LOA) biases and precision between the wearable and ambulatory devices over 24 hours were 0.5 (-10.1 to 11.1) mm Hg for SBP and 2.24 (-17.6 to 13.1) mm Hg for DBP. The mean biases (LOA) and precision between the wearable and home device over 7 days were -12.7 (-28.7 to 3.4) mm Hg for SBP and -5.6 (-20.5 to 9.2) mm Hg for DBP. The wearable BP device was well accepted by participants who found the device easy to wear and use. Both participants and health care providers agreed that the wearable cuffless devices were easy to use and that they could be used to improve BP monitoring., Conclusions: Wearable BP measures compared well against a gold-standard ambulatory device, indicating potential for this user-friendly method to augment BP management, particularly by enabling long-term monitoring that could improve treatment titration and increase understanding of users' BP response during daily activity and stressors., (©Sheikh Mohammed Shariful Islam, Susie Cartledge, Chandan Karmakar, Jonathan Charles Rawstorn, Steve F Fraser, Clara Chow, Ralph Maddison. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.10.2019.)

Purpose: Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk., Methods: Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise., Results: Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, -16%; ET, -7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R = 0.47, P < 0.01)., Conclusion: Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function., Clinical Trial Registration: ACTRN12616001602415.

Patients with end-stage kidney disease on dialysis have increased mortality and reduced physical activity, contributing to impaired physical function. Although exercise programs have demonstrated a positive effect on physiological outcomes such as cardiovascular function and strength, there is a reduced focus on physical function. The aim of this review was to determine whether exercise programs improve objective measures of physical function indicative of activities of daily living for patients with end-stage kidney disease on dialysis. A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature identified 27 randomized control trials. Only randomized control trials using an exercise intervention or significant muscular activation in the intervention, a usual care, nonexercising control group, and at least one objective measure of physical function were included. Participants were ≥18 yr of age, with end-stage kidney disease, undergoing hemo- or peritoneal dialysis. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration's tool for assessing risk bias. A meta-analysis was completed for the 6-min walk test. Data from 27 studies with 1,156 participants showed that exercise, regardless of modality, generally increased 6-min walk test distance, sit-to-stand time or repetitions, and grip strength as well as step and stair climb times or repetitions, dynamic mobility, and short physical performance battery scores. From the evidence available, exercise, regardless of modality, improved objective measures of physical function for end-stage kidney disease patients undergoing dialysis. It is acknowledged that further well-designed randomized control trials are required.

Background: Osteoporosis and related fragility fractures are a global public health problem in which pharmaceutical agents targeting bone mineral density (BMD) are the first line of treatment. However, pharmaceuticals have no effect on improving other key fracture risk factors, including low muscle strength, power and functional capacity, all of which are associated with an increased risk for falls and fracture, independent of BMD. Targeted exercise training is the only strategy that can simultaneously improve multiple skeletal and fall-related risk factors, but it must be appropriately prescribed and tailored to the desired outcome(s) and the specified target group., Objectives: In this review, we provide an overview of the general principles of training and specific loading characteristics underlying current exercise guidelines for the prevention of osteoporosis, and an update on the latest scientific evidence with regard to the type and dose of exercise shown to positively influence bone mass, structure and strength and reduce fracture risk in postmenopausal women., (Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background: Nutrition and physical activity interventions are important components of cancer care. With an increasing demand for services, there is a need to consider flexible, easily accessible, and tailored models of care while maintaining optimal outcomes., Objective: This systematic review describes and appraises the efficacy of technology-supported self-guided nutrition and physical activity interventions for people with cancer., Methods: A systematic search of multiple databases from 1973 to July 2018 was conducted for randomized and nonrandomized trials investigating technology-supported self-guided nutrition and physical activity interventions. Risk of bias was assessed using the Cochrane Risk of Bias tool. Outcomes included behavioural, health-related, clinical, health service, or financial measures., Results: Sixteen randomized controlled trials representing 2684 participants were included. Most studies were web-based interventions (n=9) and had a 12-week follow-up duration (n=8). Seven studies assessed dietary behaviour, of which two reported a significant benefit on diet quality or fruit and vegetable intake. Fifteen studies measured physical activity behaviour, of which eight studies reported a significant improvement in muscle strength and moderate-to-vigorous physical activity. Four of the nine studies assessing the health-related quality of life (HRQoL) reported a significant improvement in global HRQoL or a domain subscale. A significant improvement in fatigue was found in four of six studies. Interpretation of findings was influenced by inadequate reporting of intervention description and compliance., Conclusions: This review identified short-term benefits of technology-supported self-guided interventions on the physical activity level and fatigue and some benefit on dietary behaviour and HRQoL in people with cancer. However, current literature demonstrates a lack of evidence for long-term benefit., Trial Registration: PROSPERO CRD42017080346; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=80346., (©Nicole Kiss, Brenton James Baguley, Kylie Ball, Robin M Daly, Steve F Fraser, Catherine L Granger, Anna Ugalde. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 12.02.2019.)

Introduction: Physical function in people on hemodialysis deteriorates significantly, however quantification of the rate of deterioration has not been well established. The aim of this study was to examine the rate of deterioration in objective physical function among end-stage kidney disease patients receiving hemodialysis., Methods: One hundred and ninety-three participants (mean age 67.5 ±13.2 years, 60.6% males) receiving hemodialysis in Australia. Objective physical function was assessed via the 30-second sit-to-stand and eight-foot timed up-and-go at baseline, 12 and 24 weeks., Findings: We found a decrease in the mean number 30-second sit-to-stands performed from 10.0 (IQR, 4.0 to 13.0); 95% CI (8.0, 11.0) to 8.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 12 weeks to 7.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 24 weeks and a significant overall decreased rate (RR = 0.82; 95% CI, 0.80 to 0.85; P < 0.001). There was a decreased performance in the eight-foot timed up-and-go time from 8.9 seconds (95% CI: 8.1 to 9.7) to 9.0 (95% CI: 8.1 to 9.7) after 12 weeks and further increasing to 9.7 (95% CI: 8.7 to 9.6) seconds after 24 weeks, and overall decreased rate (HR = 0.56; 95% CI, 0.39 to 0.80; P = 0.001) between baseline and week 24., Discussion: Physical function significantly decreases on hemodialysis. Exercise programs to address this physical function decline should be included in hemodialysis treatment regimens., (© 2017 International Society for Hemodialysis.)

Purpose: Certain cancer treatments are associated with bone loss and increased fracture risk. Weight-bearing impact exercise, resistance training or the combination, are recommended to preserve or improve bone mineral density (BMD) inhealthy older adults, but their efficacy in cancer survivors is less well understood. The aim of this systematic review with meta-analysis of randomised control trials (RCT) was to review the evidence regarding the role of exercise to counteract cancer treatment-induced bone loss., Methods: Four databases were searched systematically with 12 RCTs of at least 6-month duration investigating the effects of exercise on BMD compared to a control group in adult cancer survivors identified., Results: Meta-analysis was completed using available data from six studies enrolling 814 participants, with lumbar spine, femoral neck and/or total hip BMD as the primary outcome measures. Overall, there was no significant benefit of exercise compared to controls on BMD at the lumbar spine (0.0071 g/cm , 95% CI -0.0002 to 0.0145, p = 0.057), femoral neck (0.0044 g/cm , 95% CI -0.0005 to 0.0093, p = 0.077), or total hip (0.0024 g/cm , 95% CI -0.0038 to 0.0086, p = 0.443). Subgroup analysis revealed a positive effect on lumbar spine BMD in three studies implementing a combined resistance and impact exercise intervention (0.015 g/cm , 95% CI 0.003 to 0.028, p = 0.019)., Conclusions: From the evidence available, exercise may not be sufficient to improve bone health in cancer survivors, but given the heterogeneity in the participant characteristics and several exercise programs which may not have been designed to specifically optimise bone health, these findings should be interpreted with caution.

Background: Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function., Methods: This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function., Discussion: This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer., Trial Registration: Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

Objective: Obesity is associated with a decline in health-related quality of life (HRQOL), while weight loss and exercise training have a positive influence. The aim of this systematic review was to compare the effects of energy restriction (ER) alone intervention to diet and exercise intervention on HRQOL., Methods: MEDLINE, CINAHL and PsycINFO databases were searched for randomised controlled trials examining HRQOL through lifestyle interventions which examined ER and energy restriction plus exercise in obese adults., Results: Nine hundred and fifty-two papers were assessed for inclusion in this review with nine being deemed suitable. This review indicates that four studies provide evidence to support the role of exercise in addition to ER to improve HRQOL in adults with obesity. The findings of this review are limited due to the limited number of studies as well as substantial heterogeneity in ER, exercise prescription variables and outcome measures utilised within studies., Conclusions: A definitive conclusion regarding the capacity of exercise to facilitate greater improvement in HRQOL than diet alone, or, to formulate an exercise prescription for obese adults to address HRQOL is not feasible based on the existing evidence. Future studies should utilise comparable HRQOL assessment tools along with ensuring full reporting of results.

Background: Exercise during haemodialysis improves strength and physical function. However, both patients and clinicians are time poor, and current exercise recommendations add an excessive time burden making exercise a rare addition to standard care. Hypothetically, blood flow restriction exercise performed during haemodialysis can provide greater value for time spent exercising, reducing this time burden while producing similar or greater outcomes. This study will explore the efficacy of blood flow restriction exercise for enhancing strength and physical function among haemodialysis patients., Methods: This is a randomised controlled trial design. A total of 75 participants will be recruited from haemodialysis clinics. Participants will be allocated to a blood flow restriction cycling group, traditional cycling group or usual care control group. Both exercising groups will complete 3 months of cycling exercise, performed intradialytically, three times per week. The blood flow restriction cycling group will complete two 10-min cycling bouts separated by a 20-min rest at a subjective effort of 15 on a 6 to 20 rating scale. This will be done with pressurised cuffs fitted proximally on the active limbs during exercise at 50% of a pre-determined limb occlusion pressure. The traditional cycling group will perform a continuous 20-min bout of exercise at a subjective effort of 12 on the same subjective effort scale. These workloads and volumes are equivalent and allow for comparison of a common blood flow restriction aerobic exercise prescription and a traditional aerobic exercise prescription. The primary outcome measures are lower limb strength, assessed by a three repetition maximum leg extension test, as well as objective measures of physical function: six-minute walk test, 30-s sit to stand, and timed up and go. Secondary outcome measures include thigh muscle cross sectional area, body composition, routine pathology, quality of life, and physical activity engagement., Discussion: This study will determine the efficacy of blood flow restriction exercise among dialysis patients for improving key physiological outcomes that impact independence and quality of life, with reduced burden on patients. This may have broader implications for other clinical populations with similarly declining muscle health and physical function, and those contraindicated to higher intensities of exercise., Trial Registration: Australian and New Zealand Clinical Trial Register: ACTRN12616000121460.

Although respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and young children, attempts to develop an effective therapy have so far proved unsuccessful. Here we report the preclinical profiles of PC786, a potent nonnucleoside RSV L protein polymerase inhibitor, designed for inhalation treatment of RSV infection. PC786 demonstrated a potent and selective antiviral activity against laboratory-adapted or clinical isolates of RSV-A (50% inhibitory concentration [IC 50 ], <0.09 to 0.71 nM) and RSV-B (IC 50 , 1.3 to 50.6 nM), which were determined by inhibition of cytopathic effects in HEp-2 cells without causing detectable cytotoxicity. The underlying inhibition of virus replication was confirmed by PCR analysis. The effects of PC786 were largely unaffected by the multiplicity of infection (MOI) and were retained in the face of established RSV replication in a time-of-addition study. Persistent anti-RSV effects of PC786 were also demonstrated in human bronchial epithelial cells. In vivo intranasal once daily dosing with PC786 was able to reduce the virus load to undetectable levels in lung homogenates from RSV-infected mice and cotton rats. Treatment with escalating concentrations identified a dominant mutation in the L protein (Y1631H) in vitro In addition, PC786 potently inhibited RSV RNA-dependent RNA polymerase (RdRp) activity in a cell-free enzyme assay and minigenome assay in HEp-2 cells (IC 50 , 2.1 and 0.5 nM, respectively). Thus, PC786 was shown to be a potent anti-RSV agent via inhibition of RdRp activity, making topical treatment with this compound a novel potential therapy for the treatment of human RSV infections., (Copyright © 2017 Coates et al.)

Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are prone to multiple treatment-induced adverse effects, particularly with regard to a deterioration in bone health and altered body composition including decreased lean tissue mass and increased fat mass. These alterations may partially explain the marked increased risk in osteoporosis, falls, fracture and cardiometabolic risk that has been observed in this population., Methods: A review was conducted that assessed standard clinical guidelines for the management of ADT-induced adverse effects on bone health and body composition in men with prostate cancer., Results: Currently, standard clinical guidelines exist for the management of various bone and metabolic ADT-induced adverse effects in men with prostate cancer. However, an evaluation of the effectiveness of these guidelines into routine practice revealed that men continued to experience increased central adiposity, and, unless pharmacotherapy was instituted, accelerated bone loss and worsening glycaemia occurred., Conclusions: This review discusses the current guidelines and some of the limitations, and proposes new recommendations based on emerging evidence regarding the efficacy of lifestyle interventions, particularly with regard to exercise and nutritional factors, to manage ADT-related adverse effects on bone health and body composition in men with prostate cancer.

The development of novel non-nucleoside inhibitors of the RSV polymerase complex is of significant clinical interest. Compounds derived from the benzothienoazepine core, such as AZ-27, are potent inhibitors of RSV viruses of the A-subgroup, but are only moderately active against the B serotype and as yet have not demonstrated activity in vivo. Herein we report the discovery of several novel families of C-2 arylated benzothienoazepine derivatives that are highly potent RSV polymerase inhibitors and reveal an exemplary structure, compound 4a, which shows low nanomolar activity against both RSV A and B viral subtypes. Furthermore, this compound is effective at suppressing viral replication, when administered intranasally, in a rodent model of RSV infection. These results suggest that compounds belonging to this chemotypes have the potential to provide superior anti-RSV agents than those currently available for clinical use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Rib fixation remains a contentious issue in the current practice of orthopaedic, trauma and thoracic surgeons. Whilst rib fractures are undoubtedly associated with high levels of morbidity and mortality, the optimal surgical approach has not yet been fully elucidated in prospective trials and the volume of procedures performed remains low., Methods: We evaluated 21 consecutive patients who underwent surgical rib fixation either via a standard thoracotomy approach or following the introduction of a video-assisted technique with minimal thoracic incisions., Results: The average age of patients undergoing rib fixation was 47 and the median length of post-operative stay was 4 days. More than 70 % of patients were found to have concurrent haemothoraces, and 19 % had significant injuries to underlying intra-thoracic structures requiring repair. One patient returned to theatre for persistent blood loss; however, there were no other immediate complications or mortalities., Conclusions: We discuss the involvement of thoracic surgeons, early assessment of the thoracic cavity with video assistance and optimal peri-operative management with particular reference to cases which demonstrate recent changes in our practice.

Androgen deprivation therapy (ADT) is an effective and widely prescribed treatment for prostate cancer (PCa), but it is associated with multiple treatment-induced adverse effects that impact on various musculoskeletal and cardiometabolic health outcomes. Emerging research has shown that ADT is also associated with cognitive impairment, which has been linked to a loss of independence, increased falls and fracture risk and greater use of medical services. The aim of this review is to outline the evidence related to the effect of ADT use on cognitive function, and propose a role for exercise training as part of usual care to prevent and/or manage cognitive impairments for PCa survivors on ADT. The following results have been obtained from this study. ADT has been shown to adversely affect specific cognitive domains, particularly verbal memory, visuomotor function, attention and executive function. However, current clinical guidelines do not recommend routine assessment of cognitive function in these men. No studies have examined whether exercise training can preserve or improve cognitive function in these men, but in healthy adults', multimodal exercise training incorporating aerobic training, progressive resistance training (PRT) and challenging motor control exercises have the potential to attenuate cognitive decline. In conclusion, as treatment with ADT for men with PCa has been associated with a decline in cognition, it is recommended that cognitive function be routinely monitored in these men and that regular exercise training be prescribed to preserve (or improve) cognitive function. Assessment of cognition and individualised exercise training should be considered in the usual treatment plan of PCa patients receiving ADT., (© 2017 Society for Endocrinology.)

Androgen deprivation therapy (ADT) is now considered a mainstay in the treatment of metastatic and locally advanced prostate cancer (PCa). Despite well-established benefits of ADT in relation to overall survival, this treatment has been associated with a number of adverse effects, particularly with regard to key cardiometabolic risk factors including the development of insulin resistance, dyslipidemia and increases in total and regional fat mass. In non-ADT populations, increased levels of visceral adipose tissue (VAT) are thought to be a key mediator of the increased cardiometabolic risk associated with weight gain, but this has received limited attention in men treated with ADT. VAT is best assessed using tools such as computed tomography or magnetic resonance imaging; however, these tools are not readily accessible for the majority of researchers or clinicians. Recent advances allow for a method of estimating VAT using a whole-body dual-energy X-ray absorptiometry (DXA) scan that shows promise as a practical tool for researchers to evaluate changes in body fat distribution during ADT. The aim of this narrative review is to (1) review the available evidence with regard to the relationship between ADT and cardiometabolic risk; (2) discuss the role of body fat distribution on cardiometabolic risk in non-ADT populations, with a particular emphasis on the importance of visceral adiposity; (3) examine the potential influence of ADT on body fat distribution and visceral adiposity and (4) provide an overview of current tools used to measure changes in body fat distribution in men treated with ADT, highlighting the potential utility of a recently developed DXA-derived measure of VAT., (© 2017 Society for Endocrinology.)

According to the 'cross stressor adaptation hypothesis', regular exercise acts as a buffer against the detrimental effects of stress. Nevertheless, evidence that higher levels of cardiorespiratory fitness moderate hemodynamic responses to acute psychological stress is inconclusive, especially in women. Women aged 30-50 years (in the mid-follicular phase of the menstrual cycle) with higher (n = 17) and lower (n = 17) levels of fitness were subjected to a Trier Social Stress Test (TSST). Continuous, non-invasive measurements were made of beat-to-beat, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), left ventricular ejection time (LVET), maximum slope, pulse interval (PI) and total peripheral resistance (TPR). Maximal oxygen consumption was significantly (p<0.001) higher in the 'higher fit' women. Lower fit women had higher fasting glucose, resting heart rate, waist to hip ratios and elevated serum triglyceride and cholesterol/ HDL ratios compared with higher fit women (p<0.05 for all). While all measured parameters (for both groups)displayed significant (p<0.001) responses to the TSST, only HR, PI and LVET differed significantly between higher and lower fit women (p<0.001 for all) with the higher fit women having the larger response in each case. It was also found that higher fit women had significantly shorter time to recovery for maximum slope compared with the lower fit women. These findings provide little support for the notion that higher levels of cardiorespiratory fitness result in lower cardiovascular responsivity to psychological stress in women but may indicate that lower fit women have blunted responses to stress., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The main purpose of this study was to investigate the effects of a 12-week, clinician-referred, community-based exercise training program with supervised and unsupervised sessions for men with prostate cancer. The secondary purpose was to determine whether androgen deprivation therapy (ADT) modified responses to exercise training., Methods: Secondary analysis was undertaken on data from a multicentre cluster randomised controlled trial in which 15 clinicians were randomly assigned to refer eligible patients to an exercise training intervention (n = 8) or to provide usual care (n = 7). Data from 119 patients (intervention n = 53, control n = 66) were available for this analysis. Outcome measures included fitness and physical function, anthropometrics, resting heart rate, and blood pressure., Results: Compared to the control condition, men in the intervention significantly improved their 6-min walk distance (M diff  = 49.98 m, p adj  = 0.001), leg strength (M diff  = 21.82 kg, p adj  = 0.001), chest strength (M diff  = 6.91 kg, p adj  = 0.001), 30-s sit-to-stand result (M diff  = 3.38 reps, p adj  = 0.001), and reach distance (M diff  = 4.8 cm, p adj  = 0.024). A significant difference (unadjusted for multiplicity) in favour of men in the intervention was also found for resting heart rate (M diff  = -3.76 beats/min, p = 0.034). ADT did not modify responses to exercise training., Conclusions: Men with prostate cancer who act upon clinician referrals to community-based exercise training programs can improve their strength, physical functioning, and, potentially, cardiovascular health, irrespective of whether or not they are treated with ADT., Implications for Cancer Survivors: Clinicians should inform men with prostate cancer about the benefits of exercise and refer them to appropriately qualified exercise practitioners and suitable community-based programs., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000609055., Competing Interests: Compliance with ethical standards Funding This study was funded by the Australian Research Council (LP100200176) and the Prostate Cancer Foundation of Australia, with in-kind support from YMCA Victoria, Eastern Health, Epworth Healthcare, North Eastern Metropolitan Integrated Cancer Service, and Peter MacCallum Cancer Centre. Conflict of interest The authors declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Understanding the factors that influence adherence to exercise programs is necessary to develop effective interventions for people with cancer. We examined the predictors of adherence to a supervised exercise program for participants in the ENGAGE study - a cluster randomized controlled trial that assessed the efficacy of a clinician-referred 12-week exercise program among men treated for prostate cancer. Demographic, clinical, behavioral, and psychosocial data from 52 participants in the intervention group were collected at baseline through self-report and medical records. Adherence to the supervised exercise program was assessed through objective attendance records. Adherence to the supervised exercise program was 80.3%. In the univariate analyses, cancer-specific quality of life subscales (role functioning r = 0.37, P = 0.01; sexual activity r = 0.26, P = 0.06; fatigue r = -0.26, P = 0.06, and hormonal symptoms r = -0.31, P = 0.03) and education (d = -0.60, P = 0.011) were associated with adherence. In the subsequent multivariate analysis, role functioning (B = 0.309, P = 0.019) and hormonal symptoms (B = -0.483, P = 0.054) independently predicted adherence. Men who experienced more severe hormonal symptoms had lower levels of adherence to the exercise program. Those who experienced more positive perceptions of their ability to perform daily tasks and leisure activities had higher levels of adherence to the exercise program. Hormonal symptoms and role functioning need to be considered when conducting exercise programs for men who have been treated for prostate cancer., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Clinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk., Methods/design: Sixty women, aged 18-50 years with a body mass index (BMI) greater than 34.9 kg.m(2) and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months., Discussion: Previous research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12611000694910 ). Date registered: 4 July 2011.

It is not clear if higher levels of cardiorespiratory fitness are associated with lower hypothalamo-pituitary adrenal (HPA) axis and sympatho-adrenal medullary (SAM) system reactivity to psychological stress in women. The association between cardio-metabolic risk markers and acute physiological responses to psychological stress in women who differ in their cardiorespiratory fitness status has also not been investigated. Women with high (n = 22) and low (n = 22) levels of fitness aged 30-50 years (in the mid-follicular phase of the menstrual cycle) were subjected to a Trier Social Stress Test (TSST) at 1500 h. Plasma concentrations of cortisol, adrenaline (Adr), noradrenaline (NA), and dopamine (DA) were measured in samples collected every 7-15 min from 1400 to 1700 h. Heart rate and blood pressure were measured at the same time points. Low-fit women had elevated serum triglyceride, cholesterol/HDL ratio, fasting glucose, and HOMA-IR levels compared with high-fit women. While cortisol, Adr, NA, HR, and blood pressure all demonstrated a significant response to the TSST, the responses of these variables did not differ significantly between high- and low-fit women in response to the TSST. Dopamine reactivity was significantly higher in the low-fit women compared with high-fit women. There was also a significant negative correlation between VO2 max and DA reactivity. These findings suggest that, for low-fit women aged 30-50 years, the response of HPA axis and SAM system to a potent acute psychological stressor is not compromised compared to that in high-fit women.

This research tested the hypothesis that women who had higher levels of physical fitness will have lower hypothalamo-pituitary-adrenal axis (cortisol) and sympatho-adrenal medullary system (blood pressure and heart rate) responses to food intake compared with women who had low levels of physical fitness. Lower fitness (n = 22; maximal oxygen consumption = 27.4 ± 1.0 mL∙kg(-1)·min(-1)) and higher fitness (n = 22; maximal oxygen consumption = 41.9 ± 1.6 mL∙kg(-1)·min(-1)) women (aged 30-50 years; in the follicular phase of the menstrual cycle) who participated in levels of physical activity that met (lower fitness = 2.7 ± 0.5 h/week) or considerably exceeded (higher fitness = 7.1 ± 1.4 h/week) physical activity guidelines made their own lunch using standardised ingredients at 1200 h. Concentrations of cortisol were measured in blood samples collected every 15 min from 1145-1400 h. Blood pressures and heart rate were also measured every 15 min between 1145 h and 1400 h. The meal consumed by the participants consisted of 20% protein, 61% carbohydrates, and 19% fat. There was a significant overall response to lunch in all of the parameters measured (time effect for all, p < 0.01). The cortisol response to lunch was not significantly different between the groups (time × treatment, p = 0.882). Overall, both groups showed the same pattern of cortisol secretion (treatment p = 0.839). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, or heart rate responses (time × treatment, p = 0.726, 0.898, 0.713, and 0.620, respectively) were also similar between higher and lower fitness women. Results suggest that the physiological response to food intake in women is quite resistant to modification by elevated physical fitness levels.

Background: The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer., Methods: This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12-week exercise program comprising 2 supervised gym sessions and 1 home-based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self-reported physical activity; the secondary outcomes were quality of life, anxiety, and symptoms of depression., Results: A significant intervention effect was observed for vigorous-intensity exercise (effect size: Cohen's d, 0.46; 95% confidence interval [CI], 0.09-0.82; P = .010) but not for combined moderate and vigorous exercise levels (effect size: d, 0.08; 95% CI, -0.28 to 0.45; P = .48). Significant intervention effects were also observed for meeting exercise guidelines (≥150 min/wk; odds ratio, 3.9; 95% CI, 1.9-7.8; P = .002); positive intervention effects were observed in the intervention group for cognitive functioning (effect size: d, 0.34; 95% CI, -0.02 to 0.70; P = .06) and depression symptoms (effect size: d, -0.35; 95% CI, -0.71 to 0.02; P = .06). Eighty percent of participants reported that the clinician's referral influenced their decision to participate in the exercise program., Conclusions: The clinician referral and 12-week exercise program significantly improved vigorous exercise levels and had a positive impact on mental health outcomes for men living with prostate cancer. Further research is needed to determine the sustainability of the exercise program and its generalizability to other cancer populations., (© 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Purpose: Androgen-deprivation therapy is a commonly used treatment for men with prostate cancer; however, the adverse effects can be detrimental to patient health and quality of life. Exercise has been proposed as a strategy for ameliorating a range of these treatment-related adverse effects. We conducted a systematic review of the literature regarding the effects of exercise on treatment-related adverse effects in men receiving androgen-deprivation therapy for prostate cancer., Methods: An online electronic search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, SPORTDiscus, and Health Source databases was performed to identify relevant peer-reviewed articles published between January 1980 and June 2013. Eligible study designs included randomized controlled trials as well as uncontrolled trials with pre- and postintervention data. Information was extracted regarding participant and exercise intervention characteristics as well as the effects of exercise on bone health, body composition, physical performance, cardiometabolic risk, fatigue, and quality of life., Results: Ten studies were included, with exercise interventions involving aerobic and/or resistance training. Exercise training demonstrated benefits in muscular strength, cardiorespiratory fitness, functional task performance, lean body mass, and fatigue, with inconsistent effects observed for adiposity. The impact of exercise on bone health, cardiometabolic risk markers, and quality of life are currently unclear., Conclusion: Among patients with prostate cancer treated with androgen-deprivation therapy, appropriately prescribed exercise is safe and may ameliorate a range of treatment-induced adverse effects. Ongoing research of high methodologic quality is required to consolidate and expand on current knowledge and to allow the development of specific evidence-based exercise prescription recommendations.

Background: Obesity is associated with impairments of physical function, cardiovascular fitness, muscle strength and the capacity to perform activities of daily living. This review examines the specific effects of exercise training in relation to body composition and physical function demonstrated by changes in cardiovascular fitness, and muscle strength when obese adults undergo energy restriction., Methods: Electronic databases were searched for randomised controlled trials comparing energy restriction plus exercise training to energy restriction alone. Studies published to May 2013 were included if they used multi-component methods for analysing body composition and assessed measures of fitness in obese adults., Results: Fourteen RCTs met the inclusion criteria. Heterogeneity of study characteristics prevented meta-analysis. Energy restriction plus exercise training was more effective than energy restriction alone for improving cardiovascular fitness, muscle strength, and increasing fat mass loss and preserving lean body mass, depending on the type of exercise training., Conclusion: Adding exercise training to energy restriction for obese middle-aged and older individuals results in favourable changes to fitness and body composition. Whilst weight loss should be encouraged for obese individuals, exercise training should be included in lifestyle interventions as it offers additional benefits.

Background: Exercise during hemodialysis treatments improves physical function, markers of cardiovascular disease and quality of life. However, exercise programs are not a part of standard therapy in the vast majority of hemodialysis clinics internationally. Hemodialysis unit-based accredited exercise physiologists may contribute to an increased intradialytic exercise uptake and improved physical function., Methods and Design: This is a stepped wedge cluster randomised controlled trial design. A total of 180 participants will be recruited from 15 community satellite hemodialysis clinics in a large metropolitan Australian city. Each clinic will represent a cluster unit. The stepped wedge design will consist of three groups each containing five randomly allocated cluster units, allocated to either 12, 24 or 36 weeks of the intervention. The intervention will consist of an accredited exercise physiologist-coordinated program consisting of six lower body resistance exercises using resistance elastic bands and tubing. The resistance exercises will include leg abduction, plantar flexion, dorsi flexion, straight-leg/bent-knee raise, knee extension and knee flexion. The resistance training will incorporate the principle of progressive overload and completed in a seated position during the first hour of hemodialysis treatment. The primary outcome measure is objective physical function measured by the 30-second sit to stand test. Secondary outcome measures include the 8-foot timed-up-and-go test, the four square step test, quality of life, cost-utility analysis, uptake and involvement in community activity, self-reported falls, fall's confidence, medication use, blood pressure and morbidity (hospital admissions)., Discussion: The results of this study are expected to determine the efficacy of an accredited exercise physiologist supervised resistance training on the physical function of people receiving hemodialysis and the cost-utility of exercise physiologists in hemodialysis centres. This may contribute to intradialytic exercise as standard therapy using an exercise physiologist workforce model., Trial Registration: Current Controlled Trials ACTRN12612001223820.

Introduction: Excessive sitting has been associated with an elevated risk of vascular conditions, particularly venous thrombosis. Interrupting sitting time with intermittent physical activity can reduce venous stasis; however, impacts on other aspects of thrombogenesis are less understood., Purpose: To examine the effects of interrupting sitting time on blood coagulation and blood volume parameters in sedentary, middle-age, overweight/obese adults (11 men and 8 women; age = 53.8 ± 4.9 yr, body mass index = 31.2 ± 4.1 kg · m(-2); mean ± SD)., Methods: The randomized three-period, three-treatment acute crossover trial consisted of uninterrupted sitting and sitting interrupted by 2-min bouts of either light- or moderate-intensity treadmill walking every 20 min. In each trial condition, blood samples were collected at baseline before the consumption of a standardized meal (-2 h) and postintervention (5 h)., Results: Plasma fibrinogen increased from baseline with uninterrupted sitting (0.24 g · L(-2), 95% confidence interval = 0.13-0.34, P < 0.001). Light-intensity but not moderate-intensity activity breaks attenuated the increase by 0.17 g · L(-1) (95% confidence interval = 0.01-0.32, P < 0.05). There were no between-condition differences in prothrombin time, activated partial thromboplastin time, von Willebrand factor, D-dimer, or platelet count. Uninterrupted sitting reduced plasma volume and increased hematocrit, hemoglobin, and red blood cell count; effects attenuated by both light- and moderate-intensity breaks (P < 0.05). White blood cell count increased with uninterrupted sitting and further increased with moderate-intensity breaks. Mean platelet volume increased with moderate-intensity but not light-intensity breaks or uninterrupted sitting., Conclusion: Uninterrupted sitting increased fibrinogen and reduced plasma volume, with associated increases in hemoglobin and hematocrit. Activity breaks attenuated these responses, indicative of an ameliorating influence on the procoagulant effects of uninterrupted sitting.

Resistance exercise is recommended as part of the exercise guidelines to prevent and manage type 2 diabetes (T2D), however, the frequency of exercise required to improve glycaemic control and insulin sensitivity is not clear. We recruited and tested 10 individuals with T2D by collecting a fasting blood sample immediately prior to, a whole-body moderate-high intensity resistance exercise session, and 24, 48 and 72 h afterwards. No changes to estimates of insulin sensitivity (HOMA2), glucose or insulin were observed using a repeated measures analysis of variance (p > 0.05). Further, there were no changes observed to markers of inflammation at 24 h following the resistance exercise session (p > 0.05). These findings suggest that insulin sensitivity is not acutely modified, positively or negatively, at 24, 48 or 72 h after a bout of resistance exercise. Nor are markers of inflammation altered during this time frame in a way that could cause transient insulin resistance., (© 2012 Blackwell Publishing Ltd.)

Aim: This study evaluates the efficacy of the Choose Health program, a family-based cognitive behavioural lifestyle program targeting improved eating and activity habits, in improving body composition, cardiovascular fitness, eating and activity behaviours in overweight and obese adolescents., Method: The sample comprised 29 male and 34 female overweight (n = 15) or obese (n = 48) adolescents aged 11.5-18.9 years (M = 14.3, SD = 1.9). Participants were randomly allocated to treatment or waitlist control conditions; waitlist condition participants were offered treatment after 6 months. DEXA-derived and anthropometric measures of body composition; laboratory-based cycle ergometer and field-assessed cardiovascular fitness data; objective and self-report physical activity measures; and self-report measures of eating habits and 7-day weighed food diaries were used to assess treatment outcome. Adherence to treatment protocols was high., Results: Treatment resulted in significant (p < .05) and sustained improvements in a range of body composition (body fat, percent body fat, lean mass) and anthropometric measures (weight, BMI, BMI-for-age z-score and percentiles). Minimal improvements were seen in cardiovascular fitness. Similar results were obtained in completer and intention-to-treat analysis. Poor adherence to assessment protocols limits conclusions that can be drawn from physical activity and dietary data., Conclusions: Participation in the Choose Health program resulted in significant improvement in body composition. Longer-term follow up is required to determine the durability of intervention effects. Alternative approaches to the measurement of diet and physical activity may be required for adolescents., (© 2013 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

Background: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency., Aim: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise., Subjects and Methods: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change., Results: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol·l⁻¹·120 min⁻¹) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol·l⁻¹·120 min⁻¹) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results., Conclusion: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia.

This paper systematically reviews the effect of resistance training (RT) on glycemic control and insulin sensitivity in adults with type 2 diabetes. Twenty studies were included, with the volume, frequency and intensity of RT varying markedly. Supervised RT improved glycemic control and insulin sensitivity, however, when supervision was removed compliance and glycemic control decreased. Evidence indicates the mechanisms behind the improvements to glucose tolerance require further elucidation. Although research demonstrates apparent benefits of RT for individuals with diabetes, further research is required to elucidate the minimum effective dose by describing frequency, intensity and the duration of acute and chronic improvements.

Background: Despite the high prevalence and negative physical and psychosocial consequences of overweight and obesity in adolescents, very little research has evaluated treatment in this population. Consequently, clinicians working with overweight and obese adolescents have little empirical research on which to base their practise. Cognitive behavioural therapy has demonstrated efficacy in promoting behaviour change in many treatment resistant disorders. Motivational interviewing has been used to increase motivation for change and improve treatment outcomes. In this paper we describe the rationale and design of a randomised controlled trial testing the efficacy of motivational interviewing and cognitive behaviour therapy in the treatment of overweight and obese adolescents., Methods: Participants took part in a motivational interview or a standard semi-structured assessment interview and were then randomly allocated to a cognitive behavioural intervention or a wait-list control condition. The cognitive behavioural intervention, the CHOOSE HEALTH Program, consisted of 13 individual treatment sessions (12 face-to-face, 1 phone call) followed by 9 maintenance sessions (7 phone calls, 2 face-to-face). Assessments were conducted prior to participation, after the treatment phase and after the maintenance phase of intervention. Improvement in body composition was the primary outcome; secondary outcomes included improved cardiovascular fitness, eating and physical activity habits, family and psychosocial functioning., Conclusion: Despite the demonstrated effectiveness of motivational interviewing and cognitive behavioural therapy in the long-term management of many treatment resistant disorders, these approaches have been under-utilised in adolescent overweight and obesity treatment. This study provides baseline data and a thorough review of the study design and treatment approach to allow for the assessment of the efficacy of motivational interviewing and cognitive behavioural therapy in the treatment of adolescent overweight and obesity. Data obtained in this study will also provide much needed information about the behavioural and psychosocial factors associated with adolescent overweight and obesity.

Lung transplant recipients (LTx) exhibit marked peripheral limitations to exercise. We investigated whether skeletal muscle Ca2+ and K+ regulation might be abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and arterialized venous plasma [K+] (where brackets denote concentration) were measured during incremental exercise. Vastus lateralis muscle was biopsied at rest and analyzed for sarcoplasmic reticulum Ca2+ release, Ca2+ uptake, and Ca2+-ATPase activity rates; fiber composition; Na+-K+-ATPase (K+-stimulated 3-O-methylfluorescein phosphatase) activity and content ([3H]ouabain binding sites); as well as for [H+] and H+-buffering capacity. Peak oxygen consumption was 47% less in LTx (P < 0.05). LTx had lower Ca2+ release (34%), Ca2+ uptake (31%), and Ca2+-ATPase activity (25%) than controls (P < 0.05), despite their higher type II fiber proportion (LTx, 75.0 +/- 5.8%; controls, 43.5 +/- 2.1%). Muscle [H+] was elevated in LTx (P < 0.01), but buffering capacity was similar to controls. Muscle 3-O-methylfluorescein phosphatase activity was 31% higher in LTx (P < 0.05), but [3H]ouabain binding content did not differ significantly. However, during exercise, the rise in plasma [K+]-to-work ratio was 2.6-fold greater in LTx (P < 0.05), indicating impaired K+ regulation. Thus grossly subnormal muscle calcium regulation, with impaired potassium regulation, may contribute to poor muscular performance in LTx.

Background: Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance., Methods: Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (VO2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK)., Results: The VO2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 +/- 0.38 vs. 6.23 +/- 0.14 mmol x L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 +/- 0.05 vs. 0.23 +/- 0.03 mmol. L-1x min-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 +/- 13.5 vs. 24.7 +/- 3.3 nmol. L-1. J-1, P < 0.001). A strong inverse relationship was found between VO2 peak and the DeltaPK. work-1 ratio (r = -0.80, N = 17, P < 0.001)., Conclusions: Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.

This study investigated whether fatiguing dynamic exercise depresses maximal in vitro Na(+)-K(+)-ATPase activity and whether any depression is attenuated with chronic training. Eight untrained (UT), eight resistance-trained (RT), and eight endurance-trained (ET) subjects performed a quadriceps fatigue test, comprising 50 maximal isokinetic contractions (180 degrees /s, 0.5 Hz). Muscle biopsies (vastus lateralis) were taken before and immediately after exercise and were analyzed for maximal in vitro Na(+)-K(+)-ATPase (K(+)-stimulated 3-O-methylfluoroscein phosphatase) activity. Resting samples were analyzed for [(3)H]ouabain binding site content, which was 16.6 and 18.3% higher (P < 0.05) in ET than RT and UT, respectively (UT 311 +/- 41, RT 302 +/- 52, ET 357 +/- 29 pmol/g wet wt). 3-O-methylfluoroscein phosphatase activity was depressed at fatigue by -13.8 +/- 4.1% (P < 0.05), with no differences between groups (UT -13 +/- 4, RT -9 +/- 6, ET -22 +/- 6%). During incremental exercise, ET had a lower ratio of rise in plasma K(+) concentration to work than UT (P < 0.05) and tended (P = 0.09) to be lower than RT (UT 18.5 +/- 2.3, RT 16.2 +/- 2.2, ET 11.8 +/- 0.4 nmol. l(-1). J(-1)). In conclusion, maximal in vitro Na(+)-K(+)-ATPase activity was depressed with fatigue, regardless of training state, suggesting that this may be an important determinant of fatigue.

Treatment with sulfamethoxazole (SMX) can lead to hypersensitivity reactions. T cells from hypersensitive patients recognize either the parent drug and/or the reactive nitroso (SMX-NO) metabolite. In this study, using a novel in vitro rat splenocyte assay, we have investigated the toxicological and immunological consequences of cell surface haptenation by SMX-NO. SMX-NO was found to be unstable in solution; spontaneous transformation yielded appreciable amounts of SMX-hydroxylamine, nitro-SMX, and the previously unknown azoxy and azo dimers within 15 min. Irreversible binding of SMX-NO to cellular protein was demonstrated by flow cytometry, with haptenation being greater on the surface of antigen-presenting cells than on T cells. The consequences of irreversible binding of SMX-NO were examined in two ways. First, haptenation above a threshold level led to a proportionate increase in cell death (both apoptosis and necrosis). Indeed, the cells that became haptenated were the same as those that underwent necrotic cell death. Second, sensitized splenocytes proliferated in the presence of major histocompatibility complex (MHC)-restricted antigen derived from both viable and dead cells haptenated with low and high levels of SMX-NO, respectively. However, direct modification of MHC by SMX-NO was not the mechanism of antigen presentation. The antigenic threshold of SMX-NO for T-cell proliferation and toxicity was estimated to be between 0.5 and 1 microM and 5 to 10 microM, respectively. The potential of SMX-NO to generate a potent antigen and cause cytotoxicity may in combination provide the signals necessary to induce a hypersensitivity reaction to SMX.

Little is known about fatigue and training effects on sarcoplasmic reticulum (SR) function in human muscle, and we therefore investigated this in eight untrained controls (UT), eight endurance-trained (ET), and eight resistance-trained athletes (RT). Muscle biopsies (vastus lateralis) taken at rest and after 50 maximal quadriceps contractions (180 degrees/s, 0.5 Hz) were analyzed for fiber composition, metabolites and maximal SR Ca(2+) release, Ca(2+) uptake, and Ca(2+)-ATPase activity. Fatigue reduced (P < 0.05) Ca(2+) release (42.1 +/- 3.8%, 43.4 +/- 3.9%, 31.3 +/- 6.1%), Ca(2+) uptake (43.0 +/- 5.2%, 34.1 +/- 4.6%, 28.4 +/- 2.8%), and Ca(2+)-ATPase activity (38.6 +/- 4.2%, 48.5 +/- 5.7%, 29.6 +/- 5.0%), in UT, RT, and ET, respectively. These decreases were correlated with fatigability and with type II fiber proportion (P < 0.05). Resting SR measures were correlated with type II proportion (r > or = 0.51, P < 0.05). ET had lower resting Ca(2+) release, Ca(2+) uptake, and Ca(2+)-ATPase (P < 0.05) than UT and RT (P < 0.05), probably because of their lower type II proportion; only minor effects were found in RT. Thus SR function is markedly depressed with fatigue in controls and in athletes, is dependent on fiber type, and appears to be minimally affected by chronic training status.

The effects of exercise-induced hypohydration on the motor skill performance of cricket bowling was examined in seven medium-fast bowlers who performed a random order of two experimental trials. Trials consisted of a bowling test (36 deliveries; PREBOWL) in a thermoneutral (16+/-2 degrees C) environment followed by approximately 1 hr of intermittent exercise in a heated environment (28+/-2 degrees C) and a further thermoneutral bowling test (36 deliveries; POSTBOWL). During one trial fluid intake was restricted (HYPO) whereas in the other, subjects were forced to drink in an effort to maintain euhydration (EUH). During all bowling tests subjects were provided with a fixed target on a cricket pitch and the line, length, and velocity of each delivery was determined. Pre-trial hydration status was confirmed by similar body mass (BM; 89.5+/-13.7 vs. 88.9+/-13.4 kg) and haemoglobin concentration (15.0+/-0.8 vs. 14.8+/-0.8 g.100 ml(-1) for EUH and HYPO, respectively). BM loss was greater in HYPO than EUH (2.48+/-0.58 vs. 0.46+/-0.45 kg). Accordingly, the resultant hypohydration was higher after HYPO than EUH (2.78+/-0.49 vs. 0.47+/-0.41% of BM). Whereas HYPO had no effect on bowling velocity (102+/-4 vs. 105+/-8 km x h(-1)), univariate analyses revealed independent differences for both bowling line (2.9+/-0.5 vs 3.4+/-0.6, P<0.01) and length (2.9+/-0.5 vs 3.4+/-0.6, P<0.01) of delivery after HYPO. We conclude that moderate (-2.8% of BM) exercise-induced hypohydration has minimal effect on maximal bowling velocity, but there is a detrimental effect on skilled motor performance in well-trained subjects.

Eight competitive oarswomen (age, 22 +/- 3 years; mass, 64.4 +/- 3.8 kg) performed three simulated 2,000-m time trials on a rowing ergometer. The trials, which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence, were conducted 1 hour after ingesting caffeine (6 or 9 mg á kg-1 body mass) or placebo. Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo (0.67 +/- 0.34 vs. 0.72 +/- 0.36 vs. 0.30 +/- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo, respectively; p <.05). Performance time improved 0.7% (95% confidence interval [CI] 0 to 1.5%) with 6 mg á kg-1 caffeine and 1. 3% (95% CI 0.5 to 2.0%) with 9 mg á kg-1 caffeine. The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose (1.53 +/- 0.52 vs.1.55 +/- 0.62 and 1. 56 +/- 0.43 min; p =.02). We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting, primarily by improving the first 500 m of a 2,000-m row.

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.

There are few published measures of Na+,K+-ATPase activity in human skeletal muscle. This study investigated the suitability of the K+-stimulated 3-O-methylfluorescein phosphatase assay for measurement of Na+,K+-ATPase activity in human skeletal muscle. Factors investigated include enzyme kinetics, sample treatment, and ligand concentration. The addition of ouabain blocked maximal K+-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase) activity, confirming the specificity of the assay. Activity was maximal using a multiple freeze-thaw treatment of the homogenate, a 10 mM KCl activating concentration, and a 3-O-methylfluorescein phosphatase substrate concentration of 160 microM, which is eight times higher than previously reported. From quadriceps muscle biopsies taken from seven healthy untrained subjects, the maximal K+-stimulated 3-O-MFPase activity determined from the homogenates was (mean +/- SE) 292 +/- 10 nmol min-1 . g-1 wet wt (1745 +/- 84 pmol min-1 . mg-1 protein). This value is five times greater than previously published data for human skeletal muscle. The intra-assay variability was 8.1% and the interassay variability was 5.3%. These modifications greatly enhanced the 3-O-MFPase assay, with the improved enzymatic conditions allowing valid, reliable measurement of Na+,K+-ATPase activity in small samples of human skeletal muscle., (Copyright 1998 Academic Press.)

Ionic regulation is critical to muscle excitation, contraction and metabolism, and thus for muscle function during exercise. This review focuses on the effects of training upon K+, Ca2+ and H+ ion regulation in muscle and K+ regulation in blood during exercise. Training enhances K+ regulation in muscle and blood and reduces muscular fatiguability. Endurance, sprint and strength training in humans induce an increased muscle Na+, K+ pump concentration, usually associated with a reduced rise in plasma [K+] during exercise. Although impaired muscle Ca2+ regulation plays a vital role in fatigue, little is known about possible training effects. In rat fast-twitch muscle, overload-induced hypertrophy and endurance training were associated with reduced sarcoplasmic reticulum Ca2+ uptake, consistent with fast-to-slow fibre transition. In human muscle, endurance and strength training had no effect on muscle Ca2+ ATPase concentration. Whilst muscle Ca2+ uptake, release and Ca2+ ATPase activity were depressed by fatigue, no differences were found between strength athletes and untrained individuals. Muscle H+ accumulation may contribute to fatigue during intense exercise and is also modified by sprint training. Sprint training may increase muscle Lac- and work output with exhaustive exercise, but the rise in muscle [H+] is unchanged or attenuated, indicating a reduced rise in muscle [H+] relative to work performed. Muscle buffering capacity can be dissociated from this improved H+ regulatory capacity after training. Thus, training enhances muscle and blood K+ and muscle H+ regulation during exercise, consistent with improved muscular performance and reduced fatiguability; however, little is known about training effects on muscle Ca2+ regulation during contraction.