Efficacy of exercise training for improving vascular dysfunction in people with cancer: a systematic review with meta-analyses.

PURPOSE: Cancer treatments exert vascular toxic effects that can lead to the development of cardiovascular disease. Exercise training has the potential to prevent or reduce cancer treatment-induced damage to vascular structure and function. This systematic review with meta-analyses aimed to determine the isolated effects of exercise training on vascular outcomes in people with cancer. METHODS: Seven electronic databases were searched on 20 September 2021 to identify randomised controlled trials, quasi-randomised trials, pilot and cohort studies. Included studies implemented a structured exercise intervention and assessed vascular structure and/or function in people during or following cancer treatment. Meta-analyses examined the effects of exercise training on endothelial function (via brachial artery flow-mediated dilation) and arterial stiffness (via pulse wave velocity). Methodological quality was assessed using the Cochrane Quality Assessment tool and modified Newcastle-Ottawa Quality Appraisal tool. Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the certainty of evidence. RESULTS: Ten studies (discussed across 11 articles) met the inclusion criteria. Methodological quality of the included studies was moderate (71% average). Exercise improved vascular function when compared to control (standardised mean difference = 0.34, 95% CI (0.01, 0.67); p = 0.044: studies = 5, participants = 171), but not pulse wave velocity (standardised mean difference = - 0.64, 95% CI (- 1.29, 0.02); p = 0.056: studies = 4, participants = 333). The certainty of evidence was moderate for flow-mediated dilation and low for pulse wave velocity. CONCLUSIONS: Compared to usual care, exercise training significantly improves flow-mediated dilation (endothelial function) but not pulse wave analysis, in people treated for cancer. IMPLICATIONS FOR CANCER SURVIVORS: Exercise may improve vascular health in individuals during and following cancer treatment.

Comparison of peripheral and cerebral vascular function between premenopausal, early and late postmenopausal females.

NEW FINDINGS: What is the central question of this study? We sought to investigate whether peripheral and cerebrovascular function are impaired in early and late postmenopausal females compared with premenopausal females, while also accounting for nitric oxide and estradiol levels. What is the main finding and its importance? We observed no differences in peripheral vascular and cerebrovascular function between healthy and physically active premenopausal females and early and late postmenopausal females. Our findings contradict previous cross-sectional observations of vascular and cerebrovascular dysfunction across menopause. Longitudinal studies assessing vascular and cerebrovascular outcomes across the menopausal transition are warranted. ABSTRACT: The risk of cardiovascular and cerebrovascular disease increases in ageing females, coinciding with the onset of menopause. Differences in peripheral and cerebrovascular function across menopausal stages, however, are poorly characterized. The aim of this study was to compare peripheral and cerebrovascular function between healthy premenopausal (PRE), early (1-6 years after final menstrual period; E-POST) and late (>6 years after final menstrual period; L-POST) postmenopausal females. We also explored the association between reproductive hormones, NO bioavailability and cerebrovascular function. In 39 females (40-65 years of age), we measured arterial stiffness, brachial artery flow-mediated dilatation, and cerebrovascular reactivity (CVR) to hypercapnia in the middle (MCAv) and internal (ICA) carotid arteries. Follicle-stimulating hormone, estradiol, progesterone and plasma nitrate and nitrite concentrations were also measured. Years since final menstrual period (PRE, 0 ± 0 years; E-POST, 3 ± 1 years; L-POST, 11 ± 4 years; P < 0.001) and estradiol levels (PRE, 145.5 ± 65.6 pg ml-1 ; E-POSTm 30.2 ± 81.2 pg ml-1 ; L-POST, 7.7 ± 11.3 pg ml-1 ; P < 0.001) were different between groups. All groups exceeded the guidelines for recommended physical activity. There were no group differences in blood pressure (P = 0.382), arterial stiffness (P = 0.129), flow-mediated dilatation (P = 0.696) or MCAv CVR (P = 0.442). The ICA CVR blood flow response was lower in PRE compared with L-POST (26.5 ± 19.2 vs. 47.8 ± 12.6%; P = 0.010), but after adjusting for age these differences were no longer present. Flow-mediated dilatation (r = 0.313, P = 0.105) and ICA CVR (r = -0.154, P = 0.495) were not associated with the estradiol concentration. There were no associations between the estradiol concentration and NO bioavailability. These results suggest that in healthy, physically active early and late postmenopausal females, vascular and cerebrovascular function is generally well preserved.

High-Intensity Interval Training is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).

Medicare reimbursed telehealth exercise physiology services were underutilised through the coronavirus (COVID-19) pandemic: an ecological study.

Objectives To describe the quantity and cost of in-person and telehealth exercise physiology (EP) reimbursed under the Medicare Benefits Schedule (MBS) in Australia before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods This study uses publicly available MBS data to describe EP services (in-person and telehealth) reimbursed by Medicare between January 2020 and December 2021. Data were extracted at state and national levels. Results Despite a reduction in quantity and cost in quartile (Q) 2 2020 (41% reduction), MBS-reimbursed EP services have remained relatively constant at a national level through the 2-year observation period. Service claims averaged 88 555 per quarter in 2020 and 95 015 in 2021. The proportion of telehealth consultations relative to total quarterly claims for EP was <1% in Q1 2020, 6.0% in Q2 2020, 2.4% in Q3 2020 and 1.7% in Q4 2020. This dropped to an average of 1.4% across 2021 (Q1-Q4). States undergoing lockdown periods reported decreased service rates relative to February 2020 (i.e. pre-lockdown). EP services were associated with a Medicare expenditure of AUD17.9M in 2020 (telehealth = 2.4% of total) and AUD19.7M (telehealth = 1.5% of total) in 2021. Conclusions Quantity and cost of MBS-reimbursed EP services remained relatively constant throughout the height of service disruption due to COVID-19 (2020/21). Telehealth uptake during this time has been minimal for EP.

Effects of fitness and fatness on age-related arterial stiffening in people with type 2 diabetes.

People with type 2 diabetes (T2D) are at a greater risk of cardiovascular disease than the general population. Both non-modifiable (age) and modifiable (low aerobic fitness, high body fatness) factors are separately predictive of cardiovascular risk, although they often occur concomitantly. This study aimed to examine the (1) association between age and arterial stiffness, a subclinical marker of cardiovascular risk; and (2) effects of body fatness and aerobic fitness on age-related increases in arterial stiffness in people with T2D. Data from 64 individuals with T2D (age 59.8 ± 8.7 years, 40% female, HbA1c 8.4 ± 1.6%) were included in this cross-sectional analysis. Carotid-femoral pulse wave velocity (cfPWV) was used to quantify arterial stiffness. Aerobic fitness (relative V̇O2peak ) was determined via indirect calorimetry during maximal exercise testing. Central body fatness was determined using waist circumference. Data were analysed using hierarchical multiple regressions. After adjustment for sex and duration of T2D, each one standard deviation (SD) increase in age (8.68 years) was associated with a 0.63 m·s-1 increase in cfPWV (ß = 0.416, p = 0.001). Following adjustment for aerobic fitness and body fatness, the standardized ß was unchanged (0.417). A one SD increase in waist circumference (13.9 cm) and relative V̇O2peak (5.3 ml·kg-1 ·min-1 ) were associated with a similar magnitude of difference in cfPWV (0.47 m·s-1 and -0.44 m·s-1 , respectively). Therefore, age is a significant correlate of increased arterial stiffness in T2D, with higher aerobic fitness attenuating, and higher body fatness exacerbating, this increase. Interventions aimed at improving cardiovascular outcomes in people with T2D should target both increased aerobic fitness and reduced body fatness.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

The Interplay between Vascular Function and Sexual Health in Prostate Cancer: The Potential Benefits of Exercise Training.

Prostate cancer and its associated treatments can cause significant and lasting morbidities, such as cardiovascular and sexual dysfunctions. Various interventions have attempted to prevent or mitigate these dysfunctions. This review summarises the available evidence on the effects of exercise training on markers of cardiovascular disease (as assessed via vascular health outcomes) and sexual health in this prevalent cancer population. Current studies predominantly report blood pressure outcomes as a marker of vascular health, as well as various questionnaires assessing sexual health parameters, in men on active treatment (i.e., hormone or radiation therapies) or post-treatment. Preliminary evidence suggests that exercise interventions may elicit improvements in sexual function, but not blood pressure, in these populations. Future studies in more advanced and varied prostate cancer populations (i.e., those on chemotherapies or immunotherapies, or undergoing active surveillance) are required to ascertain the duration, intensity and frequency of exercise that optimises the effects of exercise training on cardiovascular and sexual dysfunctions (and their relationship) in men during and following treatment for prostate cancer.

A 12-month lifestyle intervention does not improve cardiac autonomic function in patients with chronic kidney disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) are at a high risk of future autonomic dysfunction and cardiovascular disease. The aim of this study was to examine the effects of a 12-month lifestyle intervention (LI) involving regular aerobic exercise on cardiac autonomic function in CKD patients. DESIGN: Pooled exploratory analysis. METHODS: 113 eligible patients with stage 3-4 CKD (eGFR 25-60 ml/min/1.75m2) participated in a LI program, including an 8-week individualised gym-based exercise program followed by a 10-month home-based program. The control (CON) group underwent standard nephrological care. The following parameters were assessed prior to and following the 12-month study period: cardiorespiratory fitness (VO2peak) from a graded exercise test; cardiac autonomic function from time, frequency, and non-linear measures of heart rate variability (HRV), heart rate (HR) recovery following peak exercise, and chronotropic competence during exercise. RESULTS: Compared to the CON group, the LI group significantly increased VO2peak (CON = -1.0 vs. LI = +1.8 ml/kg/min, p < 0.01) while there was no significant improvement in any HRV measure (p = 0.85), HR recovery (p = 0.38) or chronotropic competence (p = 0.28). Changes in relative VO2peak were significantly associated with changes in a non-linear HRV measure, α1 (p < 0.01), independent of age and eGFR (r2 = 0.196, p = 0.03). CONCLUSIONS: Despite the significant increase in cardiorespiratory fitness for the LI group, there were no changes in cardiac autonomic function. However, α1 may be a sensitive measure to assess VO2peak changes in this clinical cohort. Further research is required to investigate the role of different modalities of exercise training to enhance cardiac autonomic function in patients with CKD.

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

CONTEXT: Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. OBJECTIVE: To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. EVIDENCE ACQUISITION: Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. EVIDENCE SYNTHESIS: A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. CONCLUSIONS: There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. PATIENT SUMMARY: Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation.

Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation.

BACKGROUND: Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease. METHODS: Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded. RESULTS: Eighty-two patients (aged 55.1 [50.6-59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7-13.4) mL·kg·min. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14-22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8-11.9]; no sepsis, 11.8 [10.5-13.8] mL·kg·min; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and ß-blocker use. CONCLUSIONS: Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease.

BACKGROUND: Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention. METHODS: One hundred forty-two participants with stage 3-4 chronic kidney disease (CKD) (eGFR 25-60 mL/min/1.73 m2) were included. Subjects were randomised to either a Control group (standard nephrological care [n = 68]) or a Lifestyle Intervention group (12 months of primarily aerobic based exercise training [n = 74]). Four eGFR formulae were compared at baseline and after 12 months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys. RESULTS: Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5 ± 8.9 ml/min/1.73m2. Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9 ± 8.5 ml/min/1.73m2. There were no significant baseline differences between the two groups. Lean mass (r = 0.319, p < 0.01) and grip strength (r = 0.391, p < 0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+ 1.9 ± 1.8 METs, p < 0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12 months. CKD-EPIcys was considerably lower in both groups at both baseline and 12 months than CKD-EPIcr (Control = - 10.5 ± 9.1 and - 13.1 ± 11.8, and Lifestyle Intervention = - 7.9 ± 8.6 and - 8.4 ± 12.3 ml/min/1.73 m2), CKD-EPIcr-cys (Control = - 3.6 ± 3.7 and - 4.5 ± 4.5, and Lifestyle Intervention = - 3.6 ± 3.7 and - 2.5 ± 5.5 ml/min/1.73 m2) and MDRDcr (Control = - 9.3 ± 8.4 and - 12.0 ± 10.7, Lifestyle Intervention = - 6.4 ± 8.4 and - 6.9 ± 11.2 ml/min/1.73 m2). CONCLUSIONS: In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12 months of exercise training. TRIAL REGISTRATION: The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered).

Divergent effects of cold water immersion versus active recovery on skeletal muscle fiber type and angiogenesis in young men.

Resistance training (RT) increases muscle fiber size and induces angiogenesis to maintain capillary density. Cold water immersion (CWI), a common postexercise recovery modality, may improve acute recovery, but it attenuates muscle hypertrophy compared with active recovery (ACT). It is unknown if CWI following RT alters muscle fiber type expression or angiogenesis. Twenty-one men strength trained for 12 wk, with either 10 min of CWI ( n = 11) or ACT ( n = 10) performed following each session. Vastus lateralis biopsies were collected at rest before and after training. Type IIx myofiber percent decreased ( P = 0.013) and type IIa myofiber percent increased with training ( P = 0.012), with no difference between groups. The number of capillaries per fiber increased from pretraining in the CWI group ( P = 0.004) but not the ACT group ( P = 0.955). Expression of myosin heavy chain genes ( MYH1 and MYH2), encoding type IIx and IIa fibers, respectively, decreased in the ACT group, whereas MYH7 (encoding type I fibers) increased in the ACT group versus CWI ( P = 0.004). Myosin heavy chain IIa protein increased with training ( P = 0.012) with no difference between groups. The proangiogenic vascular endothelial growth factor protein decreased posttraining in the ACT group versus CWI ( P < 0.001), whereas antiangiogenic Sprouty-related, EVH1 domain-containing protein 1 protein increased with training in both groups ( P = 0.015). Expression of microRNAs that regulate muscle fiber type (miR-208b and -499a) and angiogenesis (miR-15a, -16, and -126) increased only in the ACT group ( P < 0.05). CWI recovery after each training session altered the angiogenic and fiber type-specific response to RT through regulation at the levels of microRNA, gene, and protein expression.

N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses.

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-ß1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.

Effect of High-Intensity Interval Training on Fitness, Fat Mass and Cardiometabolic Biomarkers in Children with Obesity: A Randomised Controlled Trial.

BACKGROUND: Paediatric obesity significantly increases the risk of developing cardiometabolic diseases across the lifespan. Increasing cardiorespiratory fitness (CRF) could mitigate this risk. High-intensity interval training (HIIT) improves CRF in clinical adult populations but the evidence in paediatric obesity is inconsistent. OBJECTIVES: The objectives of this study were to determine the efficacy of a 12-week, HIIT intervention for increasing CRF and reducing adiposity in children with obesity. METHODS: Children with obesity (n = 99, 7-16 years old) were randomised into a 12-week intervention as follows: (1) HIIT [n = 33, 4 × 4-min bouts at 85-95% maximum heart rate (HRmax), interspersed with 3 min of active recovery at 50-70% HRmax, 3 times/week] and nutrition advice; (2) moderate-intensity continuous training (MICT) [n = 32, 44 min at 60-70% HRmax, 3 times/week] and nutrition advice; and (3) nutrition advice only (nutrition) [n = 34]. CRF was quantified through a maximal exercise test ([Formula: see text]) while adiposity was assessed using magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and air-displacement plethysmography. RESULTS: HIIT stimulated significant increases in relative [Formula: see text] compared with MICT (+3.6 mL/kg/min, 95% CI 1.1-6.0, P = 0.004) and the nutrition intervention (+5.4 mL/kg/min, 95% CI 2.9-7.9, P = 0.001). However, the intervention had no significant effect on visceral and subcutaneous adipose tissue, whole body composition or cardiometabolic biomarkers (P > 0.05). CONCLUSION: A 12-week, HIIT intervention was highly effective in increasing cardiorespiratory fitness when compared with MICT and nutrition interventions. While there were no concomitant reductions in adiposity or blood biomarkers, the cardiometabolic health benefit conferred through increased CRF should be noted. CLINICAL TRIALS REGISTRATION NUMBER: Clinicaltrials.gov; NCT01991106.

The Correlates of Kidney Dysfunction ­ Tumour Nephrectomy Database (CKD-TUNED) Study: Protocol for a Prospective Observational Study

Background: Tumour nephrectomy conveys a significant risk of adverse renal functional outcomes postoperatively, however there are limited strategies for predicting patients at increased risk of these outcomes. The Correlates of Kidney Dysfunction ­ Tumour Nephrectomy Database (CKD-TUNED) study is a prospective observational study evaluating the risk of chronic kidney disease and end-stage kidney disease in tumour nephrectomy patients. Methods: The CKDTUNED study involves analysis of clinical data and collection of tissue, urine and blood samples for the purposes of forming a tissue repository resource for future investigation. Recruitment began in 2013 and is expected to continue until 2023, with a projected sample size between 700-1000 subjects. Results: All relevant ethics and site-specific approvals have been granted and all relevant infrastructure is in place. Study methods are undergoing validation and refinement. As of June 2017 there are 267 participants enrolled in the study. Conclusion: It is anticipated that this study will have the potential to identify risk factors for adverse renal functional outcomes following tumour nephrectomy, which can be used in the development of predictive models with clinical utility, and in turn improve patient outcomes.

Factors associated with acutely elevated serum creatinine following radical tumour nephrectomy: the Correlates of Kidney Dysfunction-Tumour Nephrectomy Database study.

BACKGROUND: To identify factors associated with acutely elevated serum creatinine (SCr) within 7 days of radical tumour nephrectomy. METHODS: The study population consisted of 130 consecutive patients managed for renal tumours. The primary outcome was acute kidney injury (AKI) (defined as SCr increase ≥50% above baseline), assessed using multivariable logistic regression analysis. The secondary outcome was SCr percentage increase, assessed using multivariable linear regression analysis. RESULTS: Following nephrectomy, the mean percentage increase in SCr in the first week was 55%±29%, and 77 (59%) patients experienced AKI. Independent predictors of AKI post-nephrectomy were male gender [adjusted odds ratio (OR): 2.67; 95% confidence interval (95% CI): 1.01, 6.93], urine albumin-creatinine ratio (OR: 0.66; 95% CI: 0.47, 0.91), preoperative estimated glomerular filtration rate (eGFR) (OR: 1.03; 95% CI: 1.00, 1.05), laparoscopic nephrectomy (OR: 3.02; 95% CI: 1.00, 9.12), and non-clear cell renal cell carcinoma (RCC) (OR: 2.93; 95% CI: 1.04, 8.29). Independent predictors of a SCr increase were male gender (ß: 12.0; 95% CI: 2.69, 21.3), urine albumin-creatinine ratio (ß: -3.36; 95% CI: -6.55, -0.16), preoperative eGFR (ß: 0.38; 95% CI: 0.10, 0.66), laparoscopic nephrectomy (ß: 12.7; 95% CI: 1.05, 24.3) and obesity (ß: 9.94, 95% CI: 0.61, 19.3). CONCLUSIONS: Male gender, albuminuria, eGFR and laparoscopic nephrectomy independently associated with acutely elevated serum creatinine following radical tumour nephrectomy.

Exercise intensity, redox homeostasis and inflammation in type 2 diabetes mellitus.

OBJECTIVES: To compare 12 weeks of exercise training at two intensities on oxidative stress, antioxidants and inflammatory biomarkers in patients with type 2 diabetes (T2D). DESIGN: Randomized trial. METHODS: Thirty-six participants with T2D were randomized to complete either 12 weeks of treadmill based high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), followed by 40 weeks of home-based training at the same intensities. Plasma inflammation, oxidative stress and antioxidant biomarkers (total F2-isoprostanes, protein carbonyls, total antioxidant capacity, glutathione peroxidase activity, interleukin-10, interleukin-6, interleukin-8 and TNF-α) were measured at baseline, 12-weeks and 1-year. RESULTS: There were no significant changes (p>0.05) in oxidative stress and inflammation biomarkers from baseline to 12-weeks in either intervention. A decrease in total antioxidant capacity in the MICT group from baseline to 1-year by 0.05mmol/L (p=0.05) was observed. There was a significant difference (p<0.05) when groups were separated by sex with females in the MICT group having a 22.1% (p<0.05) decrease in protein carbonyls from baseline to 1-year. CONCLUSIONS: HIIT and MICT had no acute effect on oxidative stress and inflammatory biomarkers in patients with T2D.

Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality?

The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements.

Assessing the effectiveness of High Intensity Interval Training (HIIT) for smoking cessation in women: HIIT to quit study protocol.

BACKGROUND: Smoking and physical inactivity are major risk factors for heart disease. Linking strategies that promote improvements in fitness and assist quitting smoking has potential to address both these risk factors simultaneously. The objective of this study is to compare the effects of two exercise interventions (high intensity interval training (HIIT) and lifestyle physical activity) on smoking cessation in female smokers. METHOD/DESIGN: This study will use a randomised controlled trial design. PARTICIPANTS: Women aged 18-55 years who smoke ≥ 5 cigarettes/day, and want to quit smoking. INTERVENTION: all participants will receive usual care for quitting smoking. Group 1--will complete two gym-based supervised HIIT sessions/week and one home-based HIIT session/week. At each training session participants will be asked to complete four 4-min (4 × 4 min) intervals at approximately 90% of maximum heart rate interspersed with 3- min recovery periods. Group 2--participants will receive a resource pack and pedometer, and will be asked to use the 10,000 steps log book to record steps and other physical activities. The aim will be to increase daily steps to 10,000 steps/day. Analysis will be intention to treat and measures will include smoking cessation, withdrawal and cravings, fitness, physical activity, and well-being. DISCUSSION: The study builds on previous research suggesting that exercise intensity may influence the efficacy of exercise as a smoking cessation intervention. The hypothesis is that HIIT will improve fitness and assist women to quit smoking. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12614001255673 (Registration date 02/12/2014).