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This study aimed to determine if percent fat-free mass loss (% FFML) after diet alone, diet plus aerobic, or diet plus resistance exercise is a predictor of weight regain in women with overweight.One hundred and forty-one premenopausal women with overweight (body mass index, 28 ± 1 kg·m -2 ; age, 35 ± 6 yr) enrolled in a weight loss program to achieve a body mass index25 kg·m -2 (diet alone, diet plus resistance, or diet plus aerobic exercise) and were followed for 1 yr. Body weight and composition (with dual-energy x-ray absorptiometry) were measured at baseline, after weight loss, and at 1 yr.Participants lost 12.1 ± 2.6 kg of body weight, 11.3 ± 2.5 kg of fat mass, and 0.5 ± 1.6 kg of fat-free mass during the weight loss intervention, followed by weight regain at 1 yr (6.0 ± 4.4 kg, 51.3% ± 37.8%; P0.001 for all). % FFML was -3.6 ± 12.4, and a greater % FFML was associated with more weight regain ( r = -0.216, P = 0.01, n = 141), even after adjusting for the intervention group ( β = -0.07; 95% confidence interval, -0.13 to -0.01; P = 0.017).% FFML is a significant predictor of weight regain in premenopausal women with overweight. These results support strategies for conserving fat-free mass during weight loss, such as resistance training. Future research should try to identify the mechanisms, at the level of both appetite and energy expenditure, responsible for this association.

Activity-related energy expenditure (AEE) correlates with physical activity volume; however, between-person differences in body size and walking economy (net V̇o2) can influence AEE. The ratio of total energy expenditure (TEE) and resting energy expenditure (REE) estimates physical activity level (PAL) relative to body mass, yet does not account for variance in walking economy. The activity-related time equivalent (ARTEwalk) circumvents such constraints by adjusting for individual-specific walking economy. Herein, we compared AEE, PAL, and ARTEwalk index in a cohort ( n = 81) of postmenopausal women while examining possible associations with biomarkers of cardiometabolic health. Secondary analyses were performed on postmenopausal women dichotomized above/below age group 50th percentile for body fat percent. TEE was reduced by 10% for the thermogenesis of digestion wherein AEE was calculated by subtracting REE from adjusted TEE. PAL was calculated as the ratio of TEE/REE. AEE was divided by the mean net energy expenditure of nongraded walking to calculate the ARTEwalk index. Between-group differences were not detected for AEE or PAL. However, the ARTEwalk index revealed that participants with less adiposity were more physically active (258 ± 149 vs. 198 ± 115 min·day−1; P = 0.046; g = 0.46). AEE and PAL did not correlate with cardiorespiratory fitness or biomarkers of cardiometabolic health. Cardiorespiratory fitness ( r = 0.32), arterial elasticity ( r = 0.24), total cholesterol/HDL-c ratio ( r = −0.22), and body fat% ( r = −0.24) were correlated with ARTEwalk. The ARTEwalk index may offer utility in detecting possible differences in physical activity volume among postmenopausal women and appears better associated with cardiometabolic biomarkers compared with AEE or PAL.

Joint specific stretch-shortening cycle (SSC) potentiation of lower extremity joints at propulsion onset during jump test performance (JTP) can temporally affect SSC potentiation. However, joint-specific SSC potentiation at propulsion onset during JTP is unknown.Twenty-two healthy young adults, 12 men and 10 women, performed: vertical jumps (a) with a preliminary countermovement (CMJ), (b) from a squat position held isometrically for 2-3 seconds at the same knee angle of CMJ (SJ), and (c) after landing from a 15 cm high platform (DJ). Kinetics and kinematics of lower extremity joints were collected. The propulsion onset was calculated uniquely for the hip, knee, and ankle joints and defined as the first positive data point (after the eccentric phase) of the joint angular velocity for each respective joint. SSC potentiation was calculated as the ratio of jump height (JH) and joint extensor moments for CMJ/SJ, DJ/SJ, and DJ/CMJ.JH ratio for CMJ/SJ, DJ/SJ, and DJ/CMJ were1 (all p0.01). Hip, knee, and ankle extensor moment ratio was1 (all p0.01) for CMJ/SJ and DJ/SJ, while for DJ/CMJ, extensor moment ratio was1 only for the ankle (p0.03). SSC potentiation was greatest at the ankle followed by the hip and knee for CMJ/SJ and DJ/SJ (all p0.05).SSC potentiation at propulsion onset was largest at the ankle followed by hip and knee. Our findings emphasize the importance of the ankle versus hip and knee joints regarding SSC potentiation at the very beginning of JTP.

Background The practical relevance of metabolic adaptation remains a controversial issue. To the best of our knowledge, no study has properly evaluated the role of metabolic adaptation in modulating weight loss outcomes. Therefore, the aim of this study was to determine the association between metabolic adaptation, at the level of resting metabolic rate (RMR), and weight and fat mass (FM) loss after low-energy diets (LED), after adjusting for dietary adherence and other confounders. Methods 71 individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 years; 33 males) were randomized to one of three 1000 kcal/day diets for 8 weeks. Body weight, FM and fat-free mass (FFM) (air displacement plethysmography), RMR (indirect calorimetry) and physical activity level (PAL) (armbands) were measured at baseline and at week 9. Metabolic adaptation at week 9 was defined as measured RMR minus predicted RMR at week 9. An equation to predict RMR was derived from baseline data of all participants that were part of this analysis and included age, sex, FM and FFM as predictors. Dietary adherence was calculated from RMR, PAL and body composition changes. Linear regression was used to assess the potential role of metabolic adaptation in predicting weight and FM loss after adjusting for dietary adherence, average PAL, sex, baseline FM and FFM and randomization group. Results Participants lost on average 14 ± 4 kg of body weight (13 ± 3%) and presented with metabolic adaptation (−92 ± 110 kcal/day, P P P 2 = 0.88, 0.93, respectively, P Conclusion In individuals with obesity, metabolic adaptation at the level of RMR is associated with less weight and FM loss in response to LED. Trial registration ID: NCT02944253.

OBJECTIVE: To investigate if combined aerobic and resistance training in older women leads to metabolic adaptation. METHODS: 80 women (64 whites, BMI: 30.0±4.4 kg/m(2), age: 64.8±3.5 years) followed 32 weeks of aerobic and resistance training. Body weight/composition (dual-energy X-ray absorptiometry) and RMR (indirect calorimetry) were measured at baseline, weeks 16 and 32. Metabolic adaptation was defined as significantly lower measured vs predicted RMR. A regression model to predict metabolic adaptation was developed including race, age, baseline fat-free mass (FFM), RMR and respiratory quotient (RQ), and changes in net submaximal oxygen consumption (VO(2)) after different tasks. RESULTS: There was significant metabolic adaptation at week 16 (−59±136 kcal/day, P=0.002), following a 640 kcal/week energy loss (−0.7±2.6 kg weight loss). In 53 women with complete data, metabolic adaptation was seen both at weeks 16 (−64±129 kcal/day, P=0.001) and 32 (−94±127 kcal/day, P

Hunter, GR, Singh, H, Martins, C, Baranauskas, MN, and Carter, SJ. Stretch-shortening cycle potentiation and resistance training-induced changes in walking economy/ease and activity-related energy expenditure in older women. J Strength Cond Res 35(5): 1345-1349, 2021-Use of elastic energy to improve economy and ease of walking may be important for older adults. The purpose of this investigation was to determine whether baseline (i.e., untrained) stretch-shortening cycle potentiation (SSCP) was associated with potential changes in free-living activity-related energy expenditure (AEE) after supervised exercise training. Sedentary, postmenopausal women (n = 64) between 60 and 74 years of age were evaluated before and after 16 weeks of combined aerobic and resistance training. Assessments included: (a) body composition (dual-energy X-ray absorptiometry), (b) resting energy expenditure (indirect calorimetry), (c) submaximal and maximal walking (treadmill/indirect calorimetry), (d) total energy expenditure (doubly labeled water), and (e) one repetition maximum performed on an incline leg press and SSCP (calculated as the difference between concentric and countermovement leg press throw). Results indicated that baseline SSCP was related (r = -0.29; p < 0.02) to changes in AEE. However, subjects who possessed a high baseline SSCP did not increase SSCP or AEE, whereas subjects with low to moderate baseline SSCP demonstrated a significant increase in both SSCP (low +0.54 and moderate +0.47 m·s-1) and AEE (low +158 and moderate +333 kcal·d-1) post-training (all p less than 0.05). Our findings suggest that among subjects with low to moderate baseline SSCP, 16 weeks of combined aerobic and resistance training can increase SSCP and free-living AEE. However, subjects with high baseline SSCP may require tailored exercise to increase SSCP and possibly AEE.

BACKGROUND The existence of metabolic adaptation, at the level of resting metabolic rate (RMR), remains highly controversial, likely due to lack of standardization of participants' energy balance. Moreover, its role as a driver of relapse remains unproven. OBJECTIVE The main aim was to determine if metabolic adaptation at the level of RMR was present after weight loss and at 1- and 2-y follow-up, with measurements taken under condition of weight stability. A secondary aim was to investigate race differences in metabolic adaptation after weight loss and if this phenomenon was associated with weight regain. METHODS A total of 171 overweight women [BMI (kg/m2): 28.3 ± 1.3; age: 35.2 ± 6.3 y; 88 whites and 83 blacks] enrolled in a weight-loss program to achieve a BMI

OBJECTIVE The aim of this study was to investigate whether baseline (pre-weight loss) metabolic variables can predict weight regain. METHODS About 117 women with overweight completed a weight loss program to achieve BMI

Background Aerobic exercise training has well established effects on increasing insulin sensitivity. However, the extent to which exercise in the absence of weight loss and/or negative energy balance results in sustained elevation in insulin sensitivity is unclear. Objective This study aimed to assess the effects of long-term aerobic exercise training on insulin sensitivity in healthy premenopausal women while controlling for energy balance. Design Female participants ages 20–40 (Mean BMI=27.0) trained three times per week throughout the study on a cycle ergometer under supervision of an exercise physiologist. Participants completed a pre-training evaluation and three post-training evaluations at times ranging from 8 to 20 weeks post-baseline, including insulin sensitivity and peak VO2 testing. Before each evaluation, participants stayed overnight in a room calorimeter for 23 h and food intake was adjusted to maintain energy balance. A cycle ergometer graded exercise test was completed after warm-up to determine peak oxygen uptake (VO2peak). Hyperinsulinemic-euglycemic clamp measures were conducted to determine insulin sensitivity. Adjusted and unadjusted models were performed for log insulin sensitivity and peak VO2 using linear model for repeated measures. Results Data from 31 participants with complete data were analyzed. The models determined that mean VO2peak (F = 5.56 (3,89) p = 0.0015) and mean insulin sensitivity (F = 3.92 (3,65) p = 0.0123) differed among timepoints. Exercise training elicited an increase in VO2peak from pre-training (25.5 ± 1.15) to all three post-training evaluations (26.7 ± 1.15 vs. 27.4 ± 1.07 vs. 27.2 ± 1.17, respectively). In contrast, insulin sensitivity increased from pre-training to first post-training evaluation, but then returned to levels not different from baseline at the subsequent two evaluations. Conclusions Improvement in insulin sensitivity resulting from exercise training appears to be transient and returns to baseline with continued training.

Insulin resistance has wide-ranging effects on metabolism, but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ∼45% of V̇o2peak, ∼63 W) and recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ∼14-wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise, regardless of pre- versus postintervention status, highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of nonoxidative fates of glucose [e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside (possible glycerolipid synthesis metabolite)], and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites (“non-self” molecules, from microbes or foods), including benzoic acid-salicylic acid-salicylaldehyde, hexadecanol-octadecanol-dodecanol, and chlorogenic acid. In addition, many nonannotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results and previously reported plasma acylcarnitine profiles support the principle that most metabolic changes during submaximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.

Aerobic capacity is negatively related to locomotion economy. The purpose of this paper is to determine what effect aerobic exercise training has on the relationship between net cycling oxygen uptake (inverse of economy) and aerobic capacity [peak oxygen uptake (V̇o2peak)], as well as what role mitochondrial coupled and uncoupled respiration may play in whole body aerobic capacity and cycling economy. Cycling net oxygen uptake and V̇o2peak were evaluated on 31 premenopausal women before exercise training (baseline) and after 8–16 wk of aerobic training. Muscle tissue was collected from 15 subjects at baseline and post-training. Mitochondrial respiration assays were performed using high-resolution respirometry. Pre- ( r = 0.46, P < 0.01) and postexercise training ( r = 0.62, P < 0.01) V̇o2peak and cycling net oxygen uptake were related. In addition, uncoupled and coupled fat respiration were related both at baseline ( r = 0.62, P < 0.01) and post-training ( r = 0.89, P < 01). Post-training coupled ( r = 0.74, P < 0.01) and uncoupled carbohydrate respiration ( r = 0.52, P < 05) were related to cycle net oxygen uptake. In addition, correlations between V̇o2peak and cycle net oxygen uptake persist both at baseline and after training, even after adjusting for submaximal cycle respiratory quotient (an index of fat oxidation). These results suggest that the negative relationship between locomotion economy and aerobic capacity is increased following exercise training. In addition, it is proposed that at least one of the primary factors influencing this relationship has its foundation within the mitochondria. Strong relationships between coupled and uncoupled respiration appear to be contributing factors for this relationship. NEW & NOTEWORTHY The negative relationship between cycle economy and aerobic capacity is increased following exercise training. The strong relationship between coupled and uncoupled respiration, especially after training, appears to be contributing to this negative relationship between aerobic capacity and cycling economy, suggesting that mitochondrial economy is not increased following aerobic exercise training. These results are suggestive that training programs designed to improve locomotion economy should focus on changing biomechanics.

Exercise is known to improve insulin sensitivity (SI); however, studies to date have been confounded by negative energy deficits after exercise. PURPOSE The primary objective of this study was to assess the effect of 8 to 16 wk of aerobic exercise training on the SI of untrained women under rigorously controlled energy-balanced conditions. The secondary objective was to determine if one acute bout of moderate-intensity continuous (MIC) or high-intensity interval (HII) exercise further affected SI. METHODS Insulin sensitivity was assessed in 28 untrained women at baseline, after 8 to 16 wk of training with no-exercise (NE) before assessment, 22 h after MIC (50% V˙O2peak), and 22 h after HII (84% V˙O2peak) using a hyperinsulinemic-euglycemic clamp. Participants were in a whole-room indirect calorimeter during each condition, and food intake was adjusted to ensure energy balance across 23 h before each clamp. RESULTS There were no significant differences in acute energy balance between each condition. Results indicated a significant main effect of time, such that SI was higher during the HII condition compared with both baseline and NE (P < 0.05). No significant differences in SI were observed after NE or MIC. CONCLUSIONS Widely reported improvements in SI in response to chronic exercise training may be mediated in part by shifts in energy balance. However, an acute bout of HII exercise may increase SI even in the context of energy balance.

Limited work has evaluated how leg press strength (LPS), relative to body mass (i.e., rLPS), affects heart rate (HR) responses during activities of daily living. Such information would prove useful by informing a specific level of rLPS needed to promote independent mobility and physical activity. Secondary analyses were performed on baseline measures of 76 untrained older (65 ± 4 y) women. After familiarization, one-repetition maximum leg press was converted to rLPS by dividing the external load lifted (kg) by body mass (BM). Participants were stratified according to percentile of age-group norms of rLPS: ≤50 % (low, ≤0.99 kg/BM, n = 15), 51-89 % (middle, 1.0-1.31 kg/BM, n = 31), and ≥90 % (high, ≥1.32 kg/BM, n = 30). HR was measured at rest and during laboratory-based tasks including fixed-speed (0.89 m·s

BackgroundFor ischaemic stroke, outcome severity is heavily time dependent. Systems of care need to be in place to ensure that patients with stroke are treated quickly and appropriately across entire health regions. Prior to this study, the province of Saskatchewan, Canada did not have a provincial stroke strategy in place.MethodsA quality improvement project was undertaken to create and evaluate a provincial stroke strategy. The Saskatchewan Acute Stroke Pathway was created using a multidisciplinary team of experts, piloted at five stroke centres and then implemented provincially. The number of stroke alerts, door-to-imaging, door-to-needle, door-to-groin puncture times and treatment rates were collected at all centres. Improvements over time were analysed using run charts and individuals control charts.ResultsThe number of stroke alerts province-wide trended upwards in the last 6 months of the study. There were no clear trends or shifts in the proportion of stroke alerts treated with alteplase or endovascular therapy. Across the province, the weighted mean door-to-imaging time decreased from 21 to 15 min, the weighted mean door-to-needle time decreased from 62 to 47 min and the mean door-to-groin puncture time decreased from 83 to 70 min. There was high variability in the degree of improvement from centre to centre.ConclusionsThe implementation of a province wide acute stroke pathway has led to improvement in stroke care on a provincial basis. Further work addressing intercentre variability is ongoing.

Regular exercise has profound metabolic influence on the liver, but effects on bile acid (BA) metabolism are less well known. BAs are synthesized exclusively in the liver from cholesterol via the rate-limiting enzyme cholesterol 7 alpha-hydroxylase (CYP7A1). BAs contribute to the solubilization and absorption of lipids and serve as important signaling molecules, capable of systemic endocrine function. Circulating BAs increase with obesity and insulin resistance, but effects following exercise and diet-induced weight loss are unknown. To test if improvements in fitness and weight loss as a result of exercise training enhance BA metabolism, we measured serum concentrations of total BAs (conjugated and unconjugated primary and secondary BAs) in sedentary, obese, insulin-resistant women (N = 11) before (PRE) and after (POST) a ∼14-wk exercise and diet-induced weight loss intervention. BAs were measured in serum collected after an overnight fast and during an oral glucose tolerance test (OGTT). Serum fibroblast growth factor 19 (FGF19; a regulator of BA synthesis) and 7-alpha-hydroxy-cholesten-3-one (C4, a marker of CYP7A1 enzymatic activity) also were measured. Using linear mixed-model analyses and the change in V̇O(2peak) (mL/min/kg) as a covariate, we observed that exercise and weight loss intervention decreased total fasting serum BA by ∼30% (P = 0.001) and increased fasting serum C4 concentrations by 55% (P = 0.004). C4 was significantly correlated with serum total BAs only in the POST condition, whereas serum FGF19 was unchanged. These data indicate that a fitness and weight loss intervention modifies BA metabolism in obese women and suggest that improved metabolic health associates with higher postabsorptive (fasting) BA synthesis. Furthermore, pre- vs. postintervention patterns of serum C4 following an OGTT support the hypothesis that responsiveness of BA synthesis to postprandial inhibition is improved after exercise and weight loss. NEW & NOTEWORTHY Exercise and weight loss in previously sedentary, insulin-resistant women facilitates a significant improvement in insulin sensitivity and fitness that may be linked to changes in bile acid metabolism. Diet-induced weight loss plus exercise-induced increases in fitness promote greater postabsorptive bile acid synthesis while also sensitizing the bile acid metabolic system to feedback inhibition during a glucose challenge when glucose and insulin are elevated.

BackgroundThe clinical relevance of metabolic adaptation remains to be fully determined, but its role as a driver of weight regain has been dismissed. It could be hypothesized that metabolic adaptation increases the length of time needed to reach weight loss goals. The aim of this study was, therefore, to determine if metabolic adaptation, at the level of resting metabolic rate (RMR), is associated with time to reach weight loss goals, after adjusting for confounders. Methods65 premenopausal women with overweight (BMI: 28.6±1.5 kg/m2; age: 36.4±5.9 years; 36 Whites and 29 Blacks) followed an 800 kcal/day diet until body mass index ≤25 kg/m2. Body weight and composition (4 compartment model (4CM) and dual x-ray absorptiometry (DXA)) and RMR (indirect calorimetry) were measured at baseline and after weight loss (after a 4-week weight stabilization period). Dietary adherence was calculated from total energy expenditure (TEE) determined by double labeled water measures and DXA body composition changes. Metabolic adaptation was defined as a significantly lower measured vs predicted RMR (from own regression model using 4CM data). A regression model to predict time to reach weight loss goals was developed including baseline body weight, baseline TEE, dietary adherence and metabolic adaptation as predictors. ResultsParticipants lost on average 12.5±3.1 kg (16.1±3.4%) over 155.1±49.2 days. Average dietary adherence was 63.6±31.0%. There was significant metabolic adaptation after weight loss (-46±113 kcal/day, P=0.002) and this variable was a significant predictor of time to reach weight loss goal (β=-0.1, P=0.033), even after adjusting for confounders (R2 adjusted = 0.59, P

Spontaneous intermittent generalized attenuations (SIGAs) are defined as a transient decrease in amplitude of electroencephalography (EEG) activity in response to a physiologic process, external stimuli, or as a result of a pathologic condition. We seek to investigate their relationship to clinical outcomes. Demographic information, modified Rankin Scale (mRS), and clinical information were noted on 22 consecutive patients with SIGAs on their EEG. 12 of the 22 patients (54.5%) died, and 12 patients (54.5%) were admitted to the intensive care unit or coronary care unit. Future studies should attempt to prospectively compare outcomes among patients with SIGAs against a control group.

Summary Background The ketone body β-hydroxybutyrate (βHB) has been shown to act as a signaling molecule that regulates metabolism and energy homeostasis during starvation in animal models. A potential association between βHB and metabolic adaptation (a reduction in energy expenditure below predicted levels) in humans has never been explored. Objective To determine if metabolic adaptation at the level of resting metabolic rate (RMR) was associated with the magnitude of ketosis induced by a very-low energy diet (VLED). A secondary aim was to investigate if the association was modulated by sex. Methods Sixty-four individuals with obesity (BMI: 34.5 ± 3.4 kg/m2; age: 45.7 ± 8.0 years; 31 males) enrolled in a 1000 kcal/day diet for 8 weeks. Body weight/composition, RMR and βHB (as a measure of ketosis) were determined at baseline and week 9 (W9). Metabolic adaptation was defined as a significantly lower measured versus predicted RMR (from own regression model). Results Participants lost on average 14.0 ± 3.9 kg and were ketotic (βHB: 0.76 ± 0.51 mM) at W9. A significant metabolic adaptation was seen (−84 ± 106 kcal/day, P Conclusion In females with obesity, but not males, the larger the [βHB] under VLED, the greater the metabolic adaptation at the level of RMR. More studies are needed to confirm these findings and to explore the mechanisms behind the sex difference in the association between ketosis and metabolic adaptation. Trial registration name Clinicaltrials.gov. Study registration ID NCT02944253. URL https://clinicaltrials.gov/ct2/show/NCT02944253 .

Very little is known about how metabolic health status, insulin resistance or metabolic challenges modulate the endocannabinoid (eCB) or polyunsaturated fatty acid (PUFA)‐derived oxylipin (OxL) lipid classes. To address these questions, plasma eCB and OxL concentrations were determined at rest, 10 and 20 min during an acute exercise bout (30 min total, ~45% of preintervention V̇O2peak, ~63 W), and following 20 min recovery in overnight‐fasted sedentary, obese, insulin‐resistant women under controlled diet conditions. We hypothesized that increased fitness and insulin sensitivity following a ~14‐week training and weight loss intervention would lead to significant changes in lipid signatures using an identical acute exercise protocol to preintervention. In the first 10 min of exercise, concentrations of a suite of OxL diols and hydroxyeicosatetraenoic acid (HETE) metabolites dropped significantly. There was no increase in 12,13‐DiHOME, previously reported to increase with exercise and proposed to activate muscle fatty acid uptake and tissue metabolism. Following weight loss intervention, exercise‐associated reductions were more pronounced for several linoleate and alpha‐linolenate metabolites including DiHOMEs, DiHODEs, KODEs, and EpODEs, and fasting concentrations of 9,10‐DiHODE, 12,13‐DiHODE, and 9,10‐DiHOME were reduced. These findings suggest that improved metabolic health modifies soluble epoxide hydrolase, cytochrome P450 epoxygenase (CYP), and lipoxygenase (LOX) systems. Acute exercise led to reductions for most eCB metabolites, with no evidence for concentration increases even at recovery. It is proposed that during submaximal aerobic exercise, nonoxidative fates of long‐chain saturated, monounsaturated, and PUFAs are attenuated in tissues that are important contributors to the blood OxL and eCB pools., The body's response to exercise involves shifts in hundreds of metabolites in tissues and blood. This study determined how specialized signaling lipids called oxylipins and endocannabinoids "respond" to an acute bout of exercise in women. Reductions in blood concentrations of many of these metabolites could signal that during submaximal aerobic exercise, flux through "non‐oxidative" pathways for fat metabolites is reduced.

NEW FINDINGS What is the central question of this study? Does the link between cardiorespiratory fitness and gut microbiota diversity persist after adjusting for the potential effects of percentage body fat and activity-related energy expenditure (AEE)? What is the main finding and its importance? This is the first study to examine the link between cardiorespiratory fitness and gut microbiota diversity while accounting for the underlying effects of percentage body fat and free-living AEE. Results from the present work suggest that cardiorespiratory fitness, not physical activity, is a superior correlate of gut microbiota diversity among post-primary treatment, non-metastatic breast cancer survivors. ABSTRACT Cancer treatment uniquely triggers multiple physiological shifts detrimental to overall health. Although previous research indicates a link between the gut microbiota and cardiorespiratory fitness, it is unclear whether these findings are attributable to potential underlying effects of percentage body fat or free-living activity energy expenditure (AEE). The microbe composition of faecal specimens from 37 breast cancer survivors was determined using 16S microbiome analyses. Individual-sample microbiota diversity (α-diversity) and between-sample community differences (β-diversity) were examined. Peak oxygen uptake ( VO2peak ) was estimated from a graded exercise test consistent with the modified Naughton protocol, in which exercise terminates at 85% of age-predicted maximal heart rate. The AEE was measured over 10 days using doubly labelled water, wherein the percentage body fat was calculated from total body water. Pearson correlations revealed α-diversity indices (Chao1, observed species, PD whole tree and Shannon) to be positively associated with VO2peak (r = 0.34-0.51; P

Objective: The purpose of this study was to examine whether the degree of ketosis, measured as plasma β-hydroxybutyrate (βHB) in fasting, was associated with changes in appetite feelings and plasma concentration of appetite-related hormones after weight loss. Methods: A total of 87 individuals with obesity (BMI: 36.5 ± 4.0 kg/m2; age: 42.4 ± 9.7 years; 39 males) underwent 8 weeks of a very low-energy diet. Body weight/composition, plasma concentration of βHB, and appetite-related hormones (active ghrelin, active glucagon-like peptide 1 [GLP-1], total peptide YY, cholecystokinin [CCK], and insulin) and subjective appetite feelings were measured at baseline and week 9. Results: Participants lost 17.7 ± 4.1 kg and were ketotic (βHB: 1.24 ± 0.82 mmol/L in fasting) at week 9. A negative association was found between βHB in fasting at week 9 and changes in basal (r = −0.315, P = 0.003) and postprandial ghrelin concentration (r = −0.286, P = 0.008), and a positive association was found with the change in postprandial GLP-1 (r = 0.244, P = 0.025) and CCK (r = 0.228, P = 0.035). No association was seen between βHB in fasting and changes in peptide YY or subjective feelings of appetite. Conclusions: βHB plasma concentration in fasting is associated with lower concentrations of the hunger hormone ghrelin and increased concentrations of the satiety hormones GLP-1 and CCK. Future studies should explore the molecular mechanisms by which βHB modulates the secretion of gut hormones.

OBJECTIVE It is unclear whether there are race-specific differences in the maintenance of skeletal muscle during energy restriction. Changes in relative skeletal muscle index (RSMI; limb lean tissue divided by height squared) were compared following (1) diet alone, (2) diet + aerobic training, or (3) diet + resistance training. METHODS Overweight, sedentary African American (AA; n = 72) and European American (EA; n = 68) women were provided an 800-kcal/d diet to reduce BMI < 25 kg/m2 . Regional fat-free mass was measured with dual-energy x-ray absorptiometry. Steady-state VO2 and heart rate responses during walking were measured. RESULTS AA women had greater RSMI and preserved RSMI during diet alone, while RSMI was significantly reduced among EA women (EA women -3.6% vs. AA women + 1.1%; P < 0.05). Diet + resistance training subjects retained RSMI (EA women + 0.2% vs. AA women + 1.4%; P = 50.05), whereas diet + aerobic training subjects decreased RSMI (EA women -1.4% vs. AA women -1.5%; P < 0.05). Maintenance of RSMI was related to delta walking ease and economy. CONCLUSIONS Compared with AA women, EA women are less muscular and lose more muscle during weight loss without resistance training. During diet-induced weight loss, resistance training preserves skeletal muscle, especially among premenopausal EA women. Maintenance of muscle during weight loss associates with better ease and economy of walking.

Age-related declines in health and function make locomotion increasingly difficult leading to reductions in non-exercise activity thermogenesis (NEAT), skeletal muscle size and strength, and increased adiposity. Exercise is an important strategy to attenuate loss of function through the life cycle. Despite claims to the contrary, high-intensity exercise is important for the prevention of obesity and sarcopenia with advancing age. Therefore, the purpose of this mini-review is to present literature supporting the contention that low volume, high-intensity aerobic and/or resistance training can slow sarcopenia, sustain ease of movement, stimulate NEAT, and attenuate the accretion of fat mass.

We hypothesized exercise training-induced improvements in ease of walking would associate with favorable changes in objectively measured physical activity (PA) and self-reported depressive symptoms following a PA behavior-change intervention in non-metastatic breast cancer survivors (BCS). Twenty-seven BCS received random assignment to an intervention (INT) or control group (CON). INT included counseling/group discussions coupled with supervised exercise tapered to unsupervised exercise. PA, depressive symptoms, and ease of walking were evaluated pre-/post-intervention using 10-day accelerometry, HADS depression subscale, and indirect calorimetry during a standardized treadmill test, respectively. PA composite score was calculated by converting weekly minutes of moderate-to-vigorous PA and average steps/day to z-scores then dividing the sum by 2. Cardiac efficiency was determined by dividing steady-state oxygen uptake by heart rate to evaluate the volume of oxygen consumed per heartbeat. ANCOVA revealed a significant time by group interaction showing the INT group exhibited greater positive changes in the PA composite compared to the CON (INT, + 0.14 ± 0.66 au vs. CON, − 0.48 ± 0.49 au; p = 0.019; η p 2 = 0.21). Changes occurring from baseline to follow-up, among all participants, revealed improved ease of walking (less oxygen uptake) associated with increased PA composite (r = − 0.52; p = 0.010) and lower depressive symptomology (r = 0.50; p = 0.012) adjusted for age, race, and months since cancer diagnosis. Increased cardiac efficiency during the standardized treadmill test also associated with less daily sedentary time (r = − 0.52; p = 0.021). These data support the assertion that reducing the physiological difficulty of walking may contribute to greater engagement in free-living PA, less sedentary time, and decreased psychosocial distress among BCS.

IntroductionResting energy expenditure (REE) increases after an intense exercise; however, little is known concerning mechanisms.PurposeThe purpose of this study was to determine effects of a single bout of moderate-intensity continuous (MIC) aerobic exercise, or high-intensity interval (HII

Calorie restriction (CR) decreases adiposity, but the magnitude and defense of weight loss is less than predicted due to reductions in total daily energy expenditure (TEE). The purpose of the current investigation was to determine whether high-intensity interval training (HIIT) would increase markers of sympathetic activation in white adipose tissue (WAT) and rescue CR-mediated reductions in EE to a greater extent than moderate-intensity aerobic exercise training (MIT). Thirty-two 5-wk-old male C57BL/6J mice were placed on ad libitum HFD for 11 wk, followed by randomization to one of four groups ( n = 8/group) for an additional 15 wk: 1) CON (remain on HFD), 2) CR (25% lower energy intake), 3) CR + HIIT (25% energy deficit created by 12.5% CR and 12.5% EE through HIIT), and 4) CR + MIT (25% energy deficit created by 12.5% CR and 12.5% EE through MIT). Markers of adipose thermogenesis ( Ucp1, Prdm16, Dio2, and Fgf21) were unchanged in either exercise group in inguinal or epididymal WAT, whereas CR + HIIT decreased Ucp1 expression in retroperitoneal WAT and brown adipose tissue. HIIT rescued CR-mediated reductions in lean body mass (LBM) and resting energy expenditure (REE), and both were associated with improvements in glucose/insulin tolerance. Improvements in glucose metabolism in the CR + HIIT group appear to be linked to a molecular signature that enhances glucose and lipid storage in skeletal muscle. Exercise performed at either moderate or high intensity does not increase markers of adipose thermogenesis when performed in the presence of CR but remodels skeletal muscle metabolic and thermogenic capacity.

Every year, approximately 62,000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2016 update of the Canadian Stroke Best Practice Recommendations Telestroke guideline is a comprehensive summary of current evidence-based and consensus-based recommendations appropriate for use by all healthcare providers and system planners who organize and provide care to patients following stroke across a broad range of settings. These recommendations focus on the use of telemedicine technologies to rapidly identify and treat appropriate patients with acute thrombolytic therapies in hospitals without stroke specialized expertise; select patients who require to immediate transfer to stroke centers for Endovascular Therapy; and for the patients who remain in community hospitals to facilitate their care on a stroke unit and provide remote access to stroke prevention and rehabilitation services. While these latter areas of Telestroke application are newer, they are rapidly developing, with new opportunities that are yet unrealized. Virtual rehabilitation therapies offer patients the opportunity to participate in rehabilitation therapies, supervised by physical and occupational therapists. While not without its limitations (e.g., access to telecommunications in remote areas, fragmentation of care), the evidence-to-date sets the foundation for improving access to care and management for patients during both the acute phase and now through post stroke recovery.

Weight regain remains the main challenge in obesity management, and its etiology remains elusive. The aim of the present review was to revise the available evidence regarding the “Compensatory Theory,” which is an explanatory model of relapse in obesity treatment, and to propose alternative mechanisms that can contribute to weight regain. It has been proposed, and generally accepted as true, that when a person loses weight the body fights back, with physiological adaptations on both sides of the energy balance equation that try to bring body weight back to its original state: this is the Compensatory Theory. This theory proposes that the increased orexigenic drive to eat and the reduced energy expenditure that follow weight loss are the main drivers of relapse. However, evidence showing a link between these physiological adaptations to weight loss and weight regain is lacking. Here, we propose that the physiological adaptations to weight loss, both at the level of the homeostatic appetite control system and energy expenditure, are in fact a normalization to a lower body weight and not drivers of weight regain. In light of this we explore other potential mechanisms, both physiological and behavioral, that can contribute to the high incidence of relapse in obesity management. More research is needed to clearly ascertain whether the changes in energy expenditure and homeostatic appetite markers seen in reduced-obese individuals are a compensatory mechanism that drives relapse or a normalization towards a lower body weight, and to explore alternative hypotheses that explain relapse in obesity management.

Background The existence of metabolic adaptation, following weight loss, remains a controversial issue. To our knowledge, no study has evaluated the role of energy balance (EB) in modulating metabolic adaptation. Objectives The aim of this study was to determine if metabolic adaptation, at the level of resting metabolic rate (RMR), is modulated by participants’ EB status. A secondary aim was to investigate if metabolic adaptation was associated with weight regain. Methods Seventy-one individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 y; 33 men) enrolled in a 1000-kcal/d diet for 8 wk, followed by 4 wk of weight stabilization and a 9-mo weight loss maintenance program. Body weight/composition and RMR were measured at baseline, week 9 (W9), week 13 (W13), and 1 y (1Y). Metabolic adaptation was defined as a significantly different (lower or higher) measured compared with predicted RMR. Results Participants lost on average 14 kg by W9, followed by weight stabilization at W13, and regained 29% of their initial weight loss at 1Y. Metabolic adaptation was found at W9 (−92 ± 110 kcal/d, P < 0.001) and W13 (−38 ± 124 kcal/d, P = 0.011) but was not correlated with weight regain. A significant reduction in metabolic adaptation was seen between W9 and W13 (−53 ± 101 kcal/d, P < 0.001). In a subset of participants who gained weight between W9 and W13 (n = 33), no metabolic adaptation was seen at W13 (−26.8 ± 121.5 kcal/d, P = 0.214). In a subset of participants with data at all time points (n = 45), metabolic adaptation was present at W9 and W13 (−107 ± 102 kcal/d, P < 0.001 and −49 ± 128 kcal/d, P = 0.013) but not at 1Y (−7 ± 129, P = 0.701). Conclusion After weight loss, metabolic adaptation at the level of RMR is dependent on the EB status of the participants, being reduced to half after a period of weight stabilization. Moreover, metabolic adaptation does not predict weight regain at 1Y follow-up. These trials were registered at clinicaltrials.gov as NCT02944253 and NCT03287726.

INTRODUCTION/PURPOSE: Aerobic exercise training (AET) has been shown to improve mitochondrial bioenergetics and upregulate proteins related to lipid metabolism. However, it remains to be determined if these alterations associated with AET persist when measured in energy balance (EB) in the days following the last bout of training.. The purpose of the study was to test the hypothesis that improvements in skeletal muscle mitochondrial function induced by AET observed in previous literature would persist when measured after restoring EB conditions 72 hours removed from the last exercise bout. METHODS: Participants were 14 premenopausal women (age = 31.2 ± 6.7 years, BMI = 26.6 ± 5.1 kg/m(2)). The AET program required 3 monitored training sessions per week for 8–16 weeks. Skeletal muscle biopsies were obtained at baseline and following 8–16 weeks of AET (≥72 hrs after the last exercise bout). All food was provided for 72 hours prior to biopsies and EB was managed 24 hours prior to testing within ±100 kcal of measured energy requirements using a whole-room calorimeter. Mitochondrial oxidative capacity was quantified in permeabilized muscle fibers from the vastus lateralis. RESULTS: We found that AET increased coupled respiration (154%) and uncoupled respiration (90%) rates using a fatty acid substrate (palmitoyl carnitine) (P

Aerobic capacity is negatively related to locomotion economy. The purpose of this paper is to determine what effect aerobic exercise training has on the relationship between net cycling oxygen uptake (inverse of economy) and aerobic capacity [peak oxygen uptake (V̇o(2peak))], as well as what role mitochondrial coupled and uncoupled respiration may play in whole body aerobic capacity and cycling economy. Cycling net oxygen uptake and V̇o(2peak) were evaluated on 31 premenopausal women before exercise training (baseline) and after 8–16 wk of aerobic training. Muscle tissue was collected from 15 subjects at baseline and post-training. Mitochondrial respiration assays were performed using high-resolution respirometry. Pre- (r = 0.46, P < 0.01) and postexercise training (r = 0.62, P < 0.01) V̇o(2peak) and cycling net oxygen uptake were related. In addition, uncoupled and coupled fat respiration were related both at baseline (r = 0.62, P < 0.01) and post-training (r = 0.89, P < 01). Post-training coupled (r = 0.74, P < 0.01) and uncoupled carbohydrate respiration (r = 0.52, P < 05) were related to cycle net oxygen uptake. In addition, correlations between V̇o(2peak) and cycle net oxygen uptake persist both at baseline and after training, even after adjusting for submaximal cycle respiratory quotient (an index of fat oxidation). These results suggest that the negative relationship between locomotion economy and aerobic capacity is increased following exercise training. In addition, it is proposed that at least one of the primary factors influencing this relationship has its foundation within the mitochondria. Strong relationships between coupled and uncoupled respiration appear to be contributing factors for this relationship. NEW & NOTEWORTHY The negative relationship between cycle economy and aerobic capacity is increased following exercise training. The strong relationship between coupled and uncoupled respiration, especially after training, appears to be contributing to this negative relationship between aerobic capacity and cycling economy, suggesting that mitochondrial economy is not increased following aerobic exercise training. These results are suggestive that training programs designed to improve locomotion economy should focus on changing biomechanics.

Hunter, GR, Neumeier, WH, Chandler-Laney, PC, Carter, SJ, Borges, JH, Hornbuckle, LM, Plaisance, EP, and Fisher, G. Ratings of perceived exertion during walking predicts endurance independent of physiological effort in older women. J Strength Cond Res 34(5): 1340-1344, 2020-This study aimed to determine whether ratings of perceived exertion (RPE) and physiological effort at different exercise intensities relate to exercise endurance. Ninety-eight sedentary women (older than 60 years) completed 3 submaximal locomotion tasks: (a) stair climbing, (b) flat walking at 2 mph, and (c) grade walking at 2 mph. Maximal treadmill endurance was measured at least 3 days before the submaximal tests. Oxygen uptake was measured during all tests, and RPE were collected for the submaximal tasks. Ratings of perceived exertion during moderate-intensity exercise (walking on the flat at 43% V[Combining Dot Above]O2max, partial R = -0.35, p0.01), but not higher intensity exercise (grade walk at 59% V[Combining Dot Above]O2max, p = 0.49, and stair climbing at 67% V[Combining Dot Above]O2max, p = 0.17), were related to endurance even after adjusting for aerobic capacity and physiological effort (composite of maximal heart rate, ventilation, and respiratory exchange ratio). However, physiological effort was significantly related to endurance for the higher intensity exercise (both grade walk and stair climbing partial R-0.24, p0.02). Similar to previous findings that subjective ratings of fatigue at rest were related to RPE during low/moderate-intensity exercise, but not higher intensity exercise, these data further support Ekkekakis's dual-mode hypothesis that cognitive factors influence RPE during low/moderate-intensity exercise. A practical application is that the coach and personal trainer should know that physiological effort seems to play a greater role in influencing endurance than RPE as intensity of exercise increases.

PURPOSE: With accelerometry, the utility to detect changes in physical activity are predicated on the assumption that walking energetics and gait mechanics do not change. The present work examined associations between changes (Δ) in walking energetics, exercise self-efficacy, and several accelerometer-derived metrics. METHODS: Secondary analyses were performed among a sub-sample (n=29) of breast cancer survivors participating in a larger randomized trial. During 4 minutes of treadmill walking (0.89 m·s(−1), 0% grade), indirect calorimetry quantified steady-state energy expenditure (EE), wherein, participants were fitted with a heart rate monitor and hip-worn triaxial accelerometer. Exercise self-efficacy was measured using a 9-item questionnaire, while vector magnitude (VM) and individual planes (e.g., mediolateral, vertical, and anteroposterior) of movement were extracted for data analyses. Evaluations were made at baseline and after 3 months. RESULTS: From baseline to 3 months, the energetic cost of walking (kcals·min(−1)) significantly decreased by an average of −5.1% (p = 0.001; d = 0.46). Conversely, VM significantly increased (p = 0.007; d = 0.53), exclusively due to greater vertical accelerations (acc) (+5.7 ± 7.8 acc; p = 0.001; d = 0.69). Changes in vertical accelerations were inversely and positively associated with Δwalking EE (r = −0.37; p = 0.047) and Δexercise self-efficacy (r = 0.39; p = 0.034), respectively. CONCLUSION: Hip-worn accelerometers do not appear well-suited to correctly detect changes in ease of walking as evidenced by reduced energetic cost. Further research should determine if a divergence between measured EE and vertical accelerations could contribute to erroneous inferences in free-living physical activity.

Introduction Endovascular therapy has revolutionized acute stroke management associated with large vessel occlusion (LVO). The province of Saskatchewan currently has 8 primary stroke centers (PSC) and 1 comprehensive stroke center (CSC) spread over a large geographical area. Seventy three percent of the population lives outside the Saskatoon metropolitan area, which houses the province’s single comprehensive stroke centre. Geography remains a significant barrier to providing endovascular therapy in a timely manner to eligible patients, knowing that the time to recanalization is a vital variable in clinical outcome. We aim to quantify the distance and time to transfer of patients to the CSC, and determine factors associated with clinically significant evolution of infarct during transfer. Methods We completed a retrospective analysis of all acute stroke patients with LVOs who were transferred from PSCs to the CSC for possible endovascular therapy in Saskatchewan from July 2016 – July 2018. Along with patient, imaging, and outcome specific factors, detailed transfer data including modality, time, and distance were collected. Results Forty-seven patients were identified as having had a LVO diagnosed at a PSC, with subsequent transfer to the CSC for endovascular therapy. The average age was 70.6 years. Of these patients, 13 (28%) underwent EVT, while 34 patients did not: 7 (15%) had clinical improvement, 12 (25%) had vessel recanalization on repeat CTA, and 15 (32%) had ASPECTS decay leading to EVT ineligibility. Distance to the PSC and distance from PSC to CSC were the most significant contributors to ASPECTS decay. Conclusion Rates of ineligibility due to ASPECTS decay were similar to those found in other regional data, despite significantly greater distances. Since the large geographic area covered by the CSC leads to a significant cost burden associated with transfers, we aim to optimize transfer protocols to better serve the outlying areas. Disclosures S. Ahmed: None. E. Noyes: None. K. Whelan: None. B. Graham: None. G. Hunter: None. M. Kelly: None. L. Peeling: None.

Background While recent clinical trials have demonstrated immense efficacy of mechanical thrombectomy in the setting of acute stroke; there remains debate over the relative safety in performing this procedure under general anesthesia (GA). Recent RCT and meta-analyses have not provided a definitive answer to this question. With the reorganization of stroke systems of care, as a result of the Saskatchewan Acute Stroke Pathway, all patients presenting with LVO are assessed and endovascular thrombectomy is performed routinely under GA. We reviewed data from our pathway to add to the data regarding safety of thrombectomy under GA. Methods Data was retrospectively reviewed on 154 consecutive LVO in 2016–2018 at the only Comprehensive stroke center in Saskatchewan. All patients undergoing MT were place under GA for the procedure. Pretreatment National Institutes of Health stroke scale (NIHSS), location of LVO and ASPECTS score were documented. Post-thrombectomy TICI scores, time to revascularization, and 90-day outcomes, both NIHSS and mRS, were recorded. Results Of 154 LVO, 147 went on to have mechanical thrombectomy (MT). 65 were right anterior circulation, 70 were left anterior circulation and 11 were posterior circulation. Of 135 anterior circulation strokes, 69 (51.1%), 58 (42.9%) and 8 (5.7%) had good, moderate and poor collateral circulation respectively, and the average pre-MT ASPECTS was 8.2. The average pre-MT NIHSS was 13.4. The average time from groin puncture to revascularization was 48.7 min. A total of 133/147 (90.4%) achieved thrombolysis in cerebral infarction (TICI) perfusion scale grade of 2b/3 after recanalization. On follow-up, 70/147 and 90/147 had documented 90-day National Institutes of Health stroke scale (NIHSS) (average = 2.4) and 90-day modified Rankin score (mRS) (average = 2.2). Overall mortality was 29/147 (19.7%). Conclusions In a high volume Comprehensive Stroke Center, general anesthesia is safe to always use mechanical thrombectomy. Outcomes of mechanical thrombectomy for LVO in are in keeping with published results for both conscious sedation and general anesthesia. This adds to the body of evidence supporting GA as a excellent option for sedation for mechanical thrombectomy. It is particularly useful in more complex cases and leads to high revascularization rates. Disclosures A. Persad: None. S. Ahmed: None. Z. Tymchak: None. R. Whelan: None. A. Gardner: None. G. Hunter: None. B. Graham: None. L. Peeling: 2; C; Medtronic. M. Kelly: 2; C; Medtronic.