Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

The role of motivation on physical activity and screen time behaviors among parent-adolescent dyads: The FLASHE study.

Behavioral theories inform the development of lifestyle interventions to address low participation in physical activity (PA); however, relatively little is known about the value of self-determination theory (SDT) for explaining screen time (ST) behaviors or in extending SDT into a dyadic context. Actor-partner (i.e., parent-adolescent) interdependence models (APIMs) allow for examination of these interpersonal relationships. The purpose of this study was to examine PA and ST among parent-adolescent dyads using the cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Parent-adolescent dyads provided responses to online surveys addressing PA (n = 1177 dyads) and ST (n = 1489 dyads) behaviors. We examined the influence of SDT-based constructs (perceived competence and motivation) on PA and ST behaviors. Structural equations were used to estimate APIMs in STATA 15.1. Full models provided a good fit to the data. For both PA and ST, perceived competence was more strongly associated with motivation among adolescents compared with parents (PA: ß = 0.72 vs. 0.58, ST: ß = 0.34 vs. 0.22, p's < 0.001). Parental motivation was associated with parental PA and both adolescent motivation for PA and ST (p's < 0.001). Parental motivation was not associated with adolescent ST-behavior. Adolescent motivation was only associated with parent motivation for PA. In the FLASHE study, SDT constructs extend acceptably to the dyadic setting, with PA models providing a slightly better fit to the data than ST models. Longitudinal studies that target perceived competence and the self-regulation of motivation in parents and their adolescents are a next logical step to understanding both PA and ST behaviors.

Social contributors to cardiometabolic diseases in indigenous populations: an international Delphi study.

OBJECTIVE: The objective of this study was to identify priority social factors contributing to indigenous cardiometabolic diseases. STUDY DESIGN: A three-round Delphi process was used to consolidate and compare the opinions of 60 experts in indigenous cardiometabolic health from Australia, New Zealand and the United States. METHODS: Round one: three open-ended questions: (i) historical, (ii) economic and (iii) sociocultural factor contributors to cardiometabolic disease risk. Round two: a structured questionnaire based on the results from the first round; items were ranked according to perceived importance. Final round: the items were reranked after receiving the summary feedback. RESULTS: Several key findings were identified: (i) an important historical factor is marginalisation and disempowerment; (ii) in terms of economic and sociocultural factors, the panellists came to the consensus that the socio-economic status and educational inequalities are important; and (iii) while consensus was not reached, economic and educational factors were also perceived to be historically influential. CONCLUSION: These findings support the need for multilevel health promotion policy. For example, tackling financial barriers that limit the access to health-promoting resources, combined with improving literacy skills to permit understanding of health education.

The effects of 4 weeks normobaric hypoxia training on microvascular responses in the forearm flexor.

Intermittent exposure to hypoxia can lead to improved endurance performance. Currently, it is unclear whether peripheral adaptions play a role in improving oxygen delivery and utilization following both training and detraining. This study aimed to characterize skeletal muscle blood flow (mBF), oxygen consumption (mV̇O2), and perfusion adaptations to i) 4-weeks handgrip training in hypoxic and normoxic conditions, and ii) following 4-weeks detraining. Using a randomised crossover design, 9 males completed 30-min handgrip training four times a week in hypoxic (14% FiO2 ~ 3250m altitude) and normoxic conditions. mBF, mV̇O2 and perfusion were assessed pre, post 4-weeks training, and following 4-weeks detraining. Hierarchical linear modelling found that mV̇O2 increased at a significantly faster rate (58%) with hypoxic training (0.09 mlO2·min-1 · 100g-1 per week); perfusion increased at a significantly (69%) faster rate with hypoxic training (3.72 µM per week). mBF did not significantly change for the normoxic condition, but there was a significant increase of 0.38 ml· min-1 · 100ml-1 per week (95% CI: 0.35, 0.40) for the hypoxic condition. During 4-weeks detraining, mV̇O2 and perfusion significantly declined at similar rates for both conditions, whereas mBF decreased significantly faster following hypoxic training. Four weeks hypoxic training increases the delivery and utilisation of oxygen in the periphery.

Differences in forearm strength, endurance, and hemodynamic kinetics between male boulderers and lead rock climbers.

This study examined differences in the oxygenation kinetics and strength and endurance characteristics of boulderers and lead sport climbers. Using near infrared spectroscopy, 13-boulderers, 10-lead climbers, and 10-controls completed assessments of oxidative capacity index and muscle oxygen consumption (m⩒O2) in the flexor digitorum profundus (FDP), and extensor digitorum communis (EDC). Additionally, forearm strength (maximal volitional contraction MVC), endurance (force-time integral FTI at 40% MVC), and forearm volume (FAV and ΔFAV) was assessed. MVC was significantly greater in boulderers compared to lead climbers (mean difference = 9.6, 95% CI 5.2-14 kg). FDP and EDC oxidative capacity indexes were significantly greater (p = .041 and .013, respectively) in lead climbers and boulderers compared to controls (mean difference = -1.166, 95% CI (-3.264 to 0.931 s) and mean difference = -1.120, 95% CI (-3.316 to 1.075 s), respectively) with no differences between climbing disciplines. Climbers had a significantly greater FTI compared to controls (mean difference = 2205, 95% CI= 1114-3296 and mean difference = 1716, 95% CI = 553-2880, respectively) but not between disciplines. There were no significant group differences in ΔFAV or m⩒O2. The greater MVC in boulderers may be due to neural adaptation and not hypertrophy. A greater oxidative capacity index in both climbing groups suggests that irrespective of climbing discipline, trainers, coaches, and practitioners should consider forearm specific aerobic training to aid performance.

A randomized controlled trial to assess the central hemodynamic response to exercise in patients with transient ischaemic attack and minor stroke.

Early exercise engagement elicits meaningful changes in peripheral blood pressure in patients diagnosed with transient ischaemic attack (TIA) or minor stroke. However, central hemodynamic markers may provide clinicians with important diagnostic and prognostic information beyond that provided by peripheral blood pressure readings. The purpose of this single-centre, randomized, parallel-group clinical trial was to determine the effect of a 12-week aerobic exercise intervention on central and peripheral hemodynamic variables in patients with TIA or minor stroke. In this study, 47 participants (66±10 years) completed a baseline assessment, which involved the measurement of central and peripheral hemodynamic parameters, undertaken in the morning, in a fasted state. Participants were randomized to either a 12-week exercise or control group on completion of the baseline assessment. An identical follow-up assessment was completed post intervention. Central hemodynamic variables were assessed using an oscillometric device at both assessments. Analysis of covariance demonstrated a significant interaction for central and peripheral blood pressure and augmentation index (all P<0.05; ηp2.09-.11), with the exercise group presenting lower values than the control group post intervention (118±17 vs 132±28 mm Hg for central blood pressure; 125±19 vs 138±28 mm Hg for peripheral blood pressure; 104±49 vs 115±67% for augmentation index). The present study demonstrates that participation in an exercise program soon after stroke/TIA diagnosis may elicit significant beneficial changes to a patient's central systolic blood pressure and augmentation index. This may positively impact upon the treatment strategies implemented by clinicians in the care of patients with TIA and minor stroke.

Long-term effectiveness of the New Zealand Green Prescription primary health care exercise initiative.

OBJECTIVES: The rising incidence of non-communicable diseases in western countries is being driven by poor lifestyle choices, including increasingly inadequate physical activity. The aim of this study was to quantify the effectiveness of a physical activity primary care intervention named the 'Green Prescription' on changes in physical activity levels 2-3 year's following original prescription. STUDY DESIGN: A retrospective study design using a telephone interview. METHODS: Physical activity and health information was gathered from participants in June-September 2015, who were originally prescribed a primary care physical activity intervention 2-3 years ago. Respondents were classified as either having completed the programme (adherence group, n = 91) or having not completed the programme (non-adherence group, n = 56). RESULTS: Participants who had completed the programme within the past 2-3 years reported an additional 64 min (95% CI = 16-110) of total physical activity per week compared to those who had dropped out. Forty-two percent of participants in the adherence group reported increased physical activity levels after receiving the Green Prescription compared to 29% in the non-adherence group. The adherence group were less likely to be sedentary (odds ratio 0.7, 95% CI = 0.5-0.9) and more likely to meet the current physical activity guidelines of at least 150 min of physical activity per week (OR = 1.1, 95% CI = 1.0-1.3). CONCLUSIONS: The findings indicate a long-term benefit is likely to participants who completed Green Prescription.

Haemodynamic kinetics and intermittent finger flexor performance in rock climbers.

Currently it is unclear whether blood flow (BF) or muscle oxidative capacity best governs performance during intermittent contractions to failure. The aim of this study was to determine oxygenation kinetics and BF responses during intermittent (10 s contraction: 3 s release) contractions at 40% of MVC in rock climbers of different ability (N=38). Total forearm BF, as well as de-oxygenation and re-oxygenation of the flexor digitorum profundus (FDP) and the flexor carpi radialis (FCR) were assessed. Compared to the control, intermediate and advanced groups, the elite climbers had a significantly (p<0.05) greater force time integral (FTI), MVC and MVC/kg. Furthermore, the elite climbers de-oxygenated the FDP significantly more during the first (7.8, 11.9, 12.4 vs. 15.7 O2%) and middle (7.3, 8.8, 10.4 vs.15.3 O2%) phases of contractions as well as for the FCR during the first phase only (8.3, 7, 11.7 vs. 13.3 O2%). They also had a significantly higher BF upon release of the contractions (656, 701, 764 vs. 971 mL ∙ min(-1)). The higher FTI seen in elite climbers may be attributable to a greater blood delivery, and an enhanced O2 recovery during the 3 s release periods, as well as a superior muscle oxidative capacity associated with the greater de-oxygenation during the 10 s contractions.

Effect of early exercise engagement on arterial stiffness in patients diagnosed with a transient ischaemic attack.

This study investigated the effects of regular exercise participation on common carotid artery stiffness in patients recently diagnosed with transient ischaemic attack (TIA). A total of 21 male and 4 female participants (mean±s.d.; 66±12 years, 1.72±0.07 m, 85.5±12.4 kg), recruited within 2 weeks of TIA diagnosis, completed a risk stratification assessment (including fasting blood glucose, cholesterol), a health history questionnaire and underwent measures of arterial stiffness (compliance and distensibility). Participants were then randomized to either an exercise (EX; 8-week intervention) or a usual-care control (CON) condition. Identical measures were obtained post intervention. Within-subject, repeated measures analysis of variance, with Condition as the between-subject factor (EX and CON), was used to assess measures of arterial stiffness at the baseline and postintervention assessment. Results revealed a significant interaction whereby an increase in compliance (0.71±0.24 vs. 0.83±0.28 mm2 kPa(-1), P=0.048, partial η2=0.159) and distensibility (15.98±5.95 vs. 19.49±6.60 10(-3) kPa(-1), P=0.023, partial η2=0.204) was observed for EX but not for CON. The present study has demonstrated that engagement in exercise soon after TIA diagnosis leads to improved large artery health. These improvements in vascular health may reduce the risk of an ensuing or recurring cardio- or cerebrovascular event.

The effect of a short-term exercise programme on haemodynamic adaptability; a randomised controlled trial with newly diagnosed transient ischaemic attack patients.

This study assessed the effect of a short-term, 8-week exercise programme on resting and exercise blood pressure (systolic (SBP); diastolic (DBP)), and other haemodynamic responses (heart rate (HR), pulse pressure (PP), double product (DP)), of newly diagnosed transient ischaemic attack (TIA) patients. Sixty-eight TIA patients completed a continuous and incremental exercise test within 2 weeks of symptom diagnosis. HR, SBP and DBP were regularly measured at rest, during exercise and in recovery. Participants were then randomised to either an 8-week exercise programme or to a usual care control group prior to completing an identical post-intervention (PI) re-assessment. Individuals randomised to the exercise condition experienced a significantly greater reduction in resting HR (-5.4±10.2%), SBP (-6.7±8.1%) and DBP (-2.8±7.2%) than the control group at the PI assessment (all P<0.05). Similar findings were demonstrated at the PI assessment when comparing haemodynamic responses during exercise (P<0.05), with significantly larger decrements observed for SBP and HR (both 10-14%), PP (17-24%) and DP (26-32%) for those randomised to the exercise intervention (all P<0.05). This study demonstrates that structured physical activity soon after TIA diagnosis will improve haemodynamic responses. The early implementation of exercise following TIA diagnosis may be an important secondary prevention strategy for this population.

Capillary cortisol sampling during high-intensity exercise.

Venepuncture is the established "gold standard" for sampling cortisol, but it is expensive, highly invasive and impractical for many experimental and clinical settings. Salivary free cortisol is a non-invasive and practical alternative; however, when cortisol concentrations exceed 500 nmol · L there is a lack of agreement between salivary (free) and venous (bound) cortisol. No known research has assessed whether capillary cortisol accurately reflects venous blood cortisol across a range of concentrations. The objective of the current study was to determine the agreement between capillary and venous blood samples of total plasma cortisol across a range of concentrations. 11 healthy male subjects (26.1 ± 5.3 years) were recruited. Capillary and venous blood samples were collected pre and post (immediately post and post 5, 10, 15 and 20 min) a treadmill VO2max test. Regression analysis revealed a strong relationship (R2=0.96, y=1.0028x + 1.2964 (P<0.05)) between capillary and venous cortisol concentrations. A Bland-Altman plot showed all data was within the upper and lower bounds of the 95% confidence interval, and no systematic bias was evident. In conclusion, capillary sampling is a valid technique for measuring bound cortisol across a range of concentrations.

Electrical stimulation-evoked resistance exercise therapy improves arterial health after chronic spinal cord injury.

STUDY DESIGN: Repeated measures training intervention. OBJECTIVES: To evaluate the effects of neuromuscular electrical stimulation (NMES)-induced resistance exercise therapy on lower extremity arterial health in individuals with chronic, complete spinal cord injury (SCI). We define "arterial health" using three surrogate markers: (a) resting diameter, (b) flow-mediated dilation (FMD), and (c) arterial range. SETTING: Department of Kinesiology, University of Georgia, USA. METHODS: We assessed five 36+/-5-year-old male individuals with chronic, complete SCI before, during, and after 18 weeks of training. The quadriceps femoris muscle group of both legs were trained twice a week with 4 x 10 repetitions of unilateral, dynamic knee extensions. The health of the posterior tibial artery was assessed using a B-mode ultrasound unit equipped with a high-resolution video capture device. Proximal occlusion was used to evoke ischemia for 5 min and then for 10 min. FMD was calculated using the peak diameter change (above rest) following 5 min occlusion. Arterial range was calculated using minimum (during occlusion) and maximum diameters (post 10 min occlusion). Hierarchical linear modeling accounted for the nested (repeated measures) experimental design. RESULTS: FMD improved from 0.08+/-0.11 mm (2.7%) to 0.18+/-0.15 mm (6.6%) (P=0.004), and arterial range improved from 0.36+/-0.28 to 0.94+/-0.40 mm (P=0.001), after 18 weeks of training. Resting diameter did not significantly change. CONCLUSIONS: Home-based, self-administered NMES resistance exercise therapy consisting of 80 contractions/week improved FMD and arterial range. This provides evidence that resistance exercise therapy can improve arterial health after SCI, which may reduce the risk of future cardiovascular disease.

Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow.

STUDY DESIGN: Longitudinal. OBJECTIVES: The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. SETTING: Academic Institution. METHODS: Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5-T10; 36+/-5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. RESULTS: Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P = 0.001). However, femoral arterial diameter did not increase. The range was 0.44+/-0.03 to 0.46+/-0.05 cm over the four time points (P = 0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. CONCLUSION: NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity.

Apical nonspecific cation channels in everted collecting tubules of potassium-adapted ambystoma.

We observed intermediate conductance channels in approximately 20% of successful patch-clamp seals made on collecting tubules dissected from Ambystoma adapted to 50 mm potassium. These channels were rarely observed in collecting tubules taken from animals which were maintained in tap water. Potassium-adaptation either leads to an increase in the number of channels present or activates quiescent channels. In cell-attached patches the conductance averaged 30.3 +/- 2.4 (9) pS. Since replacement of the chloride in the patch pipette with gluconate did not change the conductance, the channel carries cations, not anions. Notably, channel activity was observed at both positive and negative pipette voltages. When the pipette was voltage clamped at 0 mV or positive voltages, the current was directed inward, consistent with the movement of sodium into the cell. The pipette voltage at which the polarity of the current reversed (movement of potassium into the pipette) was -29.6 +/- 6.5(9) mV. Open probability at 0 mV pipette voltage was 0.08 +/- 0.03 and was unaffected when the apical membrane was exposed to either 2 x 10(-6) or 2 x 10(-5) m of amiloride. Exposure of the basolateral surface of the tubule to a saline containing 15 mm potassium caused a significant increase (P less than 0.001) in the open probability of these channels to 0.139 +/- 0.002 without affecting the conductance of the apical channel. These data illustrate the presence of an intermediate conductance, poorly selective, amiloride-insensitive cation channel in native vertebrate collecting tubule. We postulate that, at least in amphibia, this channel may be used to secrete potassium.