Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke.

OBJECTIVE: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health. DESIGN: Randomized controlled trial. SETTING: The general communities of Baltimore, Maryland, and Atlanta, Georgia. PARTICIPANTS: Two hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246). INTERVENTION: Participants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;). MAIN OUTCOME MEASURE(S): Peak oxygen uptake rate (V̇o2peak), 6-minute walking distance (6MWD), fasting plasma glucose, insulin, oxidative stress, and inflammatory biomarkers were assessed pre- and postintervention. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. RESULTS: Physical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V̇o2peak: -9% vs 24%, P<.01; 6MWD: 1% vs 15%, P=.05; insulin: -1% vs -31%, P=.05; HOMA-IR: -3% vs -29%, P=.06). Plasma concentrations of nitrotyrosine, protein carbonyls, and oxidized low-density lipoprotein (oxLDL) tended to decrease from pre-intervention concentrations in response to TM compared to ST (ST vs TM: nitrotyrosine: 2% vs -28%, P=.01; protein carbonyls: -4% vs -34%, P=.08; oxLDL: -3% vs -32%, P<.01). Changes in circulating concentrations of C-reactive protein, protein carbonyls, and oxLDL were negatively associated with changes in V̇o2peak and 6MWD (r's=-0.40 to -0.76) and positively associated with fasting plasma insulin and HOMA-IR (r's=0.52-0.81, Ps<.01). CONCLUSIONS: Six months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.

CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke.

BACKGROUND AND PURPOSE: Reduced number and function of CD31+ circulating angiogenic cells (CACs) may explain vascular complications associated with the chronic phase stroke. The purpose of this study was to quantify CD31+ CAC paracrine function, total number and number of various subtypes of CD31+ CACs in individuals with chronic stroke compared with controls. METHODS: Peripheral blood mononuclear cells were isolated from chronic stroke participants and controls. CD31+ cells were quantified by flow cytometry, as was co-expression of CD31 in combination with CD14, CD3, CD11b, or CD34. Immunomagnetically selected CD31+ cells were cultured, and conditioned medium was used in a capillary-like network assay. RESULTS: Significantly lower levels of CD31+ CACs were found in stroke participants compared with controls (-24%; P=0.04). Additionally, CD31+/CD14+, CD31+/CD11b+ and CD31+/CD3+ cells were significantly lower in the chronic stroke group compared with controls (-45%, P=0.02; -47%, P=0.02 and -32%, P=0.03, respectively). There was no group effect on CD31+ CAC conditioned media-mediated capillary-like network formation. CONCLUSION: CD31+ CACs and subtypes may serve as potential therapeutic targets in chronic stroke recovery.

Insulin Resistance in Skeletal Muscle of Chronic Stroke.

A stroke can lead to reduced mobility affecting skeletal muscle mass and fatty infiltration which could lead to systemic insulin resistance, but this has not been examined and the mechanisms are currently unknown. The objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in paretic (P) and nonparetic (NP) skeletal muscle in chronic stroke, and to compare to nonstroke controls. Participants were mild to moderately disabled adults with chronic stroke (n = 30, 60 ± 8 years) and sedentary controls (n = 35, 62 ± 8 years). Insulin sensitivity (M) and bilateral GS activity were determined after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Stroke subjects had lower aerobic capacity than controls, but M was not significantly different. Insulin-stimulated activities of GS (independent, total, fractional), as well as absolute differences (insulin minus basal) and the percent change (insulin minus basal, relative to basal) in GS activities, were all significantly lower in P versus NP muscle. Basal GS fractional activity was 3-fold higher, and the increase in GS fractional activity during the clamp was 2-fold higher in control versus P and NP muscle. Visceral fat and intermuscular fat were associated with lower M. The effect of in vivo insulin to increase GS fractional activity was associated with M in control and P muscle. A reduction in insulin action on GS in paretic muscle likely contributes to skeletal muscle-specific insulin resistance in chronic stroke.

Vitamin K Intake in Chronic Stroke: Implications for Dietary Recommendations.

Previous research has identified a possible association between vitamin K intake and cardiometabolic disease. This could mean that the assessment of vitamin K intake is a meaningful tool when monitoring individuals with preexisting cardiovascular disease. Sixty chronic stroke survivors (men and women, body mass index (BMI) 30.36 ± 6.61 kg/m2, age 61.7 ± 7.2 years) completed food records which were analyzed for energy, macronutrient, micronutrient, and food group servings. Participants were divided into two groups: below vitamin K recommendation (BEL, n = 49) and met vitamin K recommendation (MET, n = 11). Energy and macronutrient intake did not differ between groups (all p > 0.127). Vegetable intake was higher in the MET group (p = 0.0001). Vitamin K intake was higher in the MET group (p = 0.0001). Calcium (p = 0.003), vitamin A (p = 0.007), and vitamin E (p = 0.005) intakes were higher in the MET group. There were no differences in sodium, potassium, vitamin D, vitamin C, and iron intakes between groups (all p > 0.212). In this sample of chronic stroke survivors, 82% reported consuming below the Dietary Reference Intake (DRI) for vitamin K. Given that the majority of this study population did not reach the DRI for vitamin K, it is advisable to promote the adequate intake of food rich in vitamin K. Further work is needed to determine the significance of low vitamin K intake in this population.

Dietary and Serum Omega-6/Omega-3 Fatty Acids Are Associated with Physical and Metabolic Function in Stroke Survivors.

The purpose of this study was to quantify habitual dietary and systemic omega-6 and omega-3 fatty acids and their ratios and to determine their relationship with physical and metabolic function in a cohort of chronic adult stroke survivors. Twenty-five older chronic stroke survivors (age: 63 ± 8 years; BMI: 31 ± 7 kg/m2; mean ± SD) were assessed for fitness (VO2peak), gait speed (GS), 3 m timed up and go (TUG), and six-minute walk distance (6MWD). Plasma lipid and glucose profiles were measured, and HOMA-IR calculated. Dietary (5-day food records) and serum (mass spectrometry) omega-6/omega-3 profiles were assessed. Participants were severely deconditioned (VO2peak: 19 ± 4 mL/kg/min; GS: 0.88 ± 0.28 m/s; TUG: 12.6 ± 5.9 s; 6MWD: 295 ± 121 m) and at elevated metabolic risk (HOMA-IR: 6.3 ± 4.5). The dietary intake ratio of omega-6/omega-3 fatty acids averaged 12.6 ± 7.1 and the serum concentration ratio was 1.21 ± 0.37, which were correlated (r = 0.88, p < 0.01). Higher dietary intake and serum concentrations of omega-6/omega-3 fatty acids were associated with lower 6MWD and higher HOMA-IR, while a higher serum omega-6/omega-3 concentration index was associated with lower VO2peak (p's < 0.05). These preliminary data suggest that both dietary omega-6 and omega-3 fatty acids (quantitated as their intake ratio) and the serum concentration ratio of omega-6/omega-3 may be important indices of physical dysfunction and insulin resistance in chronic stroke survivors.

Aerobic Exercise Recommendations to Optimize Best Practices in Care After Stroke: AEROBICS 2019 Update.

Most stroke survivors have very low levels of cardiovascular fitness, which limits mobility and leads to further physical deconditioning, increased sedentary behavior, and heightened risk of recurrent stroke. Although clinical guidelines recommend that aerobic exercise be a part of routine stroke rehabilitation, clinical uptake has been suboptimal. In 2013, an international group of stroke rehabilitation experts developed a user-friendly set of recommendations to guide screening and prescription-the Aerobic Exercise Recommendations to Optimize Best Practices in Care after Stroke (AEROBICS 2013). The objective of this project was to update AEROBICS 2013 using the highest quality of evidence currently available. The first step was to conduct a comprehensive review of literature from 2012 to 2018 related to aerobic exercise poststroke. A working group of the original consensus panel members drafted revisions based on synthesis. An iterative process was used to achieve agreement among all panel members. Final revisions included: (1) addition of 115 new references to replace or augment those in the original AEROBICS document, (2) rewording of the original recommendations and supporting material, and (3) addition of 2 new recommendations regarding prescription. The quality of evidence from which these recommendations were derived ranged from low to high. The AEROBICS 2019 Update should make it easier for clinicians to screen for, and prescribe, aerobic exercise in stroke rehabilitation. Clinical implementation will not only help to narrow the gap between evidence and practice but also reduce current variability and uncertainty regarding the role of aerobic exercise in recovery after stroke.

Metabolomics of Aerobic Exercise in Chronic Stroke Survivors: A Pilot Study.

BACKGROUND: Understanding the metabolic response to exercise may aid in optimizing stroke management. Therefore, the purpose of this pilot study was to evaluate plasma metabolomic profiles in chronic stroke survivors following aerobic exercise training. METHODS: Participants (age: 62 ± 1 years, body mass index: 31 ± 1 kg/m2, mean ± standard error of the mean) were randomized to 6 months of treadmill exercise (N = 17) or whole-body stretching (N = 8) with preintervention and postintervention measurement of aerobic capacity (VO2peak). Linear models for microarray data expression analysis was performed to determine metabolic changes over time, and Mummichog was used for pathway enrichment analysis following analysis of plasma samples by high-performance liquid chromatography coupled to ultrahigh resolution mass spectrometry. RESULTS: VO2peak change was greater following exercise than stretching (18.9% versus -.2%; P < .01). Pathway enrichment analysis of differentially expressed metabolites results showed significant enrichment in 4 pathways following treadmill exercise, 3 of which (heparan-, chondroitin-, keratan-sulfate degradation) involved connective tissue metabolism and the fourth involve lipid signaling (linoleate metabolism). More pathways were altered in pre and post comparisons of stretching, including branched-chain amino acid, tryptophan, tyrosine, and urea cycle, which could indicate loss of lean body mass. CONCLUSIONS: These preliminary data show different metabolic changes due to treadmill training and stretching in chronic stroke survivors and suggest that in addition to improved aerobic capacity, weight-bearing activity, like walking, could protect against loss of lean body mass. Future studies are needed to examine the relationship between changes in metabolomic profiles to reductions in cardiometabolic risk after treadmill rehabilitation.

Brain-derived neurotrophic factor, epigenetics in stroke skeletal muscle, and exercise training.

OBJECTIVE: (1) To compare paretic (P) vs nonparetic (NP) skeletal muscle brain-derived neurotrophic factor (BDNF) and the effects of resistive training (RT) on systemic and skeletal muscle BDNF mRNA expression in stroke; and (2) to compare the DNA methylation profile for BDNF and BDNFAS (BDNF antisense RNA) between P and NP muscle and the effects of aerobic exercise training (AEX) on DNA methylation in stroke. METHODS: In this longitudinal investigation, participants (50-76 years) with chronic stroke underwent a fasting blood draw, a 12-week (3×/week) RT intervention (n = 16), and repeated bilateral vastus lateralis muscle tissue biopsies (n = 10) with BDNF expression determined by RT-PCR. Five stroke survivors completed 6 months of AEX (3×/week) and had bilateral muscle biopsies. DNA methylation status in gene BDNF and BDNFAS was assessed by Illumina 450k methylation array. RESULTS: P muscle had ∼45% lower BDNF mRNA expression than NP muscle (6.79 ± 1.30 vs 10.52 ± 2.06 arbitrary units [AU], p < 0.05), and P muscle exhibited differential methylation status in the DNA sequences of BDNF (3 CpG [5'-C-phosphate-G-3'] sites, p = 0.016-0.044) and BDNFAS (1 CpG site, p = 0.016) compared to NP. Plasma BDNF and muscle BDNF messenger RNA (mRNA) expression did not significantly change after RT. BDNFAS DNA methylation increased after AEX in P relative to NP muscle (p = 0.017). CONCLUSIONS: This is the first evidence that stroke hemiparesis reduces BDNF skeletal muscle expression, with our findings identifying methylation alterations on the DNA sequence of BDNF and BDNFAS gene. Preliminary results further indicate that AEX increases methylation in BDNFAS gene, which presumably could regulate the expression of BDNF.

Type 2 diabetes and older age contribute to elevated plasma microparticle concentrations independent of chronic stroke.

NEW FINDINGS: What is the central question of this study? What is the effect of chronic stroke on circulating microparticle populations, accounting for potential effects of age and type 2 diabetes? What is the main finding and its importance? Elevated concentrations of CD31+ /CD42b- and CD62E+ microparticles appear to be driven by type 2 diabetes but not chronic stroke and are associated with fasting glucose and triglyceride levels. Older age results in elevations in CD62E+ and CD34+ microparticle concentrations. These microparticles have been proposed as potential targets for diagnosing, treating and identifying the clinical progression and complications of type 2 diabetes. ABSTRACT: The elevated circulating concentration of endothelial microparticles (MPs) may provide an index of the extent and nature of cellular damage in chronic stroke. The purpose of this study was to determine the circulating concentrations of CD31+ /CD42b- , CD62E+ and CD34+ MPs in chronic stroke subjects, focusing on the effects of chronic stroke by comparison with both older adults without a history of stroke but with type 2 diabetes mellitus (T2DM) and older and young healthy controls. Plasma from three groups of sedentary older (50-75 years) men and women (chronic stroke, T2DM or older healthy) as well as a group of younger (18-39 years) healthy controls was isolated from fasting blood, and CD31+ /CD42b- , CD62E+ and CD34+ MPs were quantified using flow cytometry (n = 17/group). Concentrations of CD31+ /CD42b- and CD62E+ MPs were higher in the T2DM group (P < 0.05), but not chronic stroke, compared to older and younger healthy adults. CD62E+ MP and CD34+ MP concentrations were elevated in the older compared to younger adults (P < 0.05 for both). Sub-analyses excluding chronic stroke subjects who were also diagnosed with diabetes [stroke (diabetes- )] revealed lower CD31+ /CD42b- (P < 0.05) and CD62E+ (P = 0.08) MPs in the stroke (diabetes- ) group compared to the T2DM group. CD31+ /CD42b- MP and CD62E+ MP concentrations were each associated with fasting glucose levels and CD31+ /CD42b- MPs also were associated with triglyceride levels. As MPs have been proposed as potential targets for diagnosing, treating and identifying the clinical progression of T2DM, our study provides further support for the use of CD31+ /CD42b- and CD62E+ MPs in the clinical progression of T2DM and associated vascular complications.

Validating accelerometry as a measure of physical activity and energy expenditure in chronic stroke.

BACKGROUND: Accelerometers can objectively measure steps taken per day in individuals without gait deficits, but accelerometers also have the ability to estimate frequency, intensity, and duration of physical activity. However, thresholds to distinguish varying levels of activity intensity using the Actical brand accelerometer are standardized only for the general population and may underestimate intensity in stroke. OBJECTIVE: To derive Actical activity count thresholds specific to stroke disability for use in more accurately gauging time spent at differing activity levels. METHODS: Men (n = 18) and women (n = 10) with chronic hemiparetic gait (4 ± 2 years latency, 43% Caucasian, 56% African-American, ages of 47-83 years, BMI 19-48 kg/m2) participated in the study. Actical accelerometers were placed on the non-paretic hip to obtain accelerometry counts during eight activities of varying intensity: (1) watching TV; (2) seated stretching; (3) standing stretching; (4) floor sweeping; (5) stepping in place; (6) over-ground walking; (7) lower speed treadmill walking (1.0 mph at 4% incline); and (8) higher speed treadmill walking (2.0 mph at 4% incline). Simultaneous portable monitoring (Cosmed K4b2) enabled quantification of energy cost for each activity in metabolic equivalents (METs, or oxygen consumption in multiples of resting level). Measurements were obtained for 10 min of standard rest and 5 min during each of the eight activities. RESULTS: Regression analysis yielded the following new stroke-specific Actical minimum thresholds: 125 counts per minute (cpm) for sedentary/light activity, 667 cpm for light/moderate activity, and 1546 cpm for moderate/vigorous activity. CONCLUSION: Our revised cut points better reflect activity levels after stroke and suggest significantly lower thresholds relative to those observed for the general population of healthy individuals. We conclude that the standard, commonly applied Actical thresholds are inappropriate for this unique population.

Resistive Training and Molecular Regulators of Vascular-Metabolic Risk in Chronic Stroke.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC-1α) gene and Sirtuin-1 (SIRT-1) respond to physiological stimuli and regulate insulin resistance. Inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and the soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1) are associated with increased risk of diabetes and coronary heart disease. Resistive training (RT) reduces hyperinsulinemia and improves insulin action in chronic stroke. Yet, the molecular mechanisms for this are unknown. This study will determine the effects of RT on skeletal muscle PGC-1α and SIRT-1 mRNA expression and inflammatory and vascular markers. METHODS: Stroke survivors (50-76 years) underwent a fasting blood draw for measurement of TNF-α, IL-6, CRP, serum amyloid A, sICAM-1, sVCAM-1, and bilateral vastus lateralis biopsies before and after RT. Participants were also assessed using bilateral multislice thigh computed tomography scans from the knee to the hip, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength testing. Subjects performed 2 sets of 3 lower extremity RT exercises 3 times per week for 12 weeks. RESULTS: Bilateral leg press and leg extension strength increased ~30-50% with RT (P < .001). Body weight, total body fat mass, and fat-free mass did not change. Thigh muscle area and volume increased in both legs (P < .05). Nonparetic muscle PGC-1α mRNA expression increased 14% (P < .05) after RT and SIRT-1 mRNA decreased 24% (P < .05) and 31% (P < .01) in paretic and nonparetic muscles. There were no significant changes in plasma inflammation with training. DISCUSSION: RT in chronic stroke induces changes in key skeletal muscle regulators of metabolism, without effecting circulating inflammation.

Sarcopenia and Physical Function in Middle-Aged and Older Stroke Survivors.

OBJECTIVES: To determine the prevalence of sarcopenia in stroke survivors using different methodologies, and compare a subset of the stroke group to age-, sex-, and body mass index (BMI)-matched nonstroke control counterparts. DESIGN: Cohort study. SETTING: A Veterans Affairs medical center and a university hospital. PARTICIPANTS: Mild to moderately disabled participants >6 months after onset of stroke aged 40 to 84 years (N=190, 61% men, 57% African American; mean BMI ± SEM, 29±1kg/m2). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using 4 established methods: (1) ALM/height2 (ALM/ht2); (2) European Working Group on Sarcopenia in Older Persons; (3) International Working Group on Sarcopenia; and (4) ALM/BMI. RESULTS: Sarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age ±4 years and BMI ±2.5kg/m2 had higher prevalence rates compared with their nonstroke counterparts (13.2% vs 5.3%, P<.0001). ALM/ht2 was related to 6-minute walking speed (r=.28, P<.01) and peak oxygen consumption (L/min: r=.58, P<.0001) for the stroke group. CONCLUSIONS: Stroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race compared with nonstroke individuals.

Strength Training for Skeletal Muscle Endurance after Stroke.

BACKGROUND AND PURPOSE: Initial studies support the use of strength training (ST) as a safe and effective intervention after stroke. Our previous work shows that relatively aggressive, higher intensity ST translates into large effect sizes for paretic and non-paretic leg muscle volume, myostatin expression, and maximum strength post-stroke. An unanswered question pertains to how our unique ST model for stroke impacts skeletal muscle endurance (SME). Thus, we now report on ST-induced adaptation in the ability to sustain isotonic muscle contraction. METHODS: Following screening and baseline testing, hemiparetic stroke participants were randomized to either ST or an attention-matched stretch control group (SC). Those in the ST group trained each leg individually to muscle failure (20 repetition sets, 3× per week for 3 months) on each of three pneumatic resistance machines (leg press, leg extension, and leg curl). Our primary outcome measure was SME, quantified as the number of submaximal weight leg press repetitions possible at a specified cadence. The secondary measures included one-repetition maximum strength, 6-minute walk distance (6MWD), 10-meter walk speeds, and peak aerobic capacity (VO2 peak). RESULTS: ST participants (N = 14) had significantly greater SME gains compared with SC participants (N = 16) in both the paretic (178% versus 12%, P < .01) and non-paretic legs (161% versus 12%, P < .01). These gains were accompanied by group differences for 6MWD (P < .05) and VO2 peak (P < .05). CONCLUSION: Our ST regimen had a large impact on the capacity to sustain submaximal muscle contraction, a metric that may carry more practical significance for stroke than the often reported measures of maximum strength.

Dynamic Balanced Reach: A Temporal and Spectral Analysis Across Increasing Performance Demands.

Standing balanced reach is a fundamental task involved in many activities of daily living that has not been well analyzed quantitatively to assess and characterize the multisegmental nature of the body's movements. We developed a dynamic balanced reach test (BRT) to analyze performance in this activity; in which a standing subject is required to maintain balance while reaching and pointing to a target disk moving across a large projection screen according to a sum-of-sines function. This tracking and balance task is made progressively more difficult by increasing the disk's overall excursion amplitude. Using kinematic and ground reaction force data from 32 young healthy subjects, we investigated how the motions of the tracking finger and whole-body center of mass (CoM) varied in response to the motion of the disk across five overall disk excursion amplitudes. Group representative performance statistics for the cohort revealed a monotonically increasing root mean squared (RMS) tracking error (RMSE) and RMS deviation (RMSD) between whole-body CoM (projected onto the ground plane) and the center of the base of support (BoS) with increasing amplitude (p < 0.03). Tracking and CoM response delays remained constant, however, at 0.5 s and 1.0 s, respectively. We also performed detailed spectral analyses of group-representative response data for each of the five overall excursion amplitudes. We derived empirical and analytical transfer functions between the motion of the disk and that of the tracking finger and CoM, computed tracking and CoM responses to a step input, and RMSE and RMSD as functions of disk frequency. We found that for frequencies less than 1.0 Hz, RMSE generally decreased, while RMSE normalized to disk motion amplitude generally increased. RMSD, on the other hand, decreased monotonically. These findings quantitatively characterize the amplitude- and frequency-dependent nature of young healthy tracking and balance in this task. The BRT is not subject to floor or ceiling effects, overcoming an important deficiency associated with most research and clinical instruments used to assess balance. This makes a comprehensive quantification of young healthy balance performance possible. The results of such analyses could be used in work space design and in fall-prevention instructional materials, for both the home and work place. Young healthy performance represents "exemplar" performance and can also be used as a reference against which to compare the performance of aging and other clinical populations at risk for falling.

Task-specific ankle robotics gait training after stroke: a randomized pilot study.

BACKGROUND: An unsettled question in the use of robotics for post-stroke gait rehabilitation is whether task-specific locomotor training is more effective than targeting individual joint impairments to improve walking function. The paretic ankle is implicated in gait instability and fall risk, but is difficult to therapeutically isolate and refractory to recovery. We hypothesize that in chronic stroke, treadmill-integrated ankle robotics training is more effective to improve gait function than robotics focused on paretic ankle impairments. FINDINGS: Participants with chronic hemiparetic gait were randomized to either six weeks of treadmill-integrated ankle robotics (n = 14) or dose-matched seated ankle robotics (n = 12) videogame training. Selected gait measures were collected at baseline, post-training, and six-week retention. Friedman, and Wilcoxon Sign Rank and Fisher's exact tests evaluated within and between group differences across time, respectively. Six weeks post-training, treadmill robotics proved more effective than seated robotics to increase walking velocity, paretic single support, paretic push-off impulse, and active dorsiflexion range of motion. Treadmill robotics durably improved gait dorsiflexion swing angle leading 6/7 initially requiring ankle braces to self-discarded them, while their unassisted paretic heel-first contacts increased from 44 % to 99.6 %, versus no change in assistive device usage (0/9) following seated robotics. CONCLUSIONS: Treadmill-integrated, but not seated ankle robotics training, durably improves gait biomechanics, reversing foot drop, restoring walking propulsion, and establishing safer foot landing in chronic stroke that may reduce reliance on assistive devices. These findings support a task-specific approach integrating adaptive ankle robotics with locomotor training to optimize mobility recovery. CLINICAL TRIAL IDENTIFIER: NCT01337960. https://clinicaltrials.gov/ct2/show/NCT01337960?term=NCT01337960&rank=1.

Skeletal muscle cellular metabolism in older HIV-infected men.

Skeletal muscle mitochondrial dysfunction may contribute to low aerobic capacity. We previously reported 40% lower aerobic capacity in HIV-infected men compared to noninfected age-matched men. The objective of this study was to compare skeletal muscle mitochondrial enzyme activities in HIV-infected men on antiretroviral therapy (55 ± 1 years of age, n = 10 African American men) with age-matched controls (55 ± 1 years of age, n = 8 Caucasian men), and determine their relationship with aerobic capacity. Activity assays for mitochondrial function including enzymes involved in fatty acid activation and oxidation, and oxidative phosphorylation, were performed in homogenates prepared from vastus lateralis muscle. Hydrogen peroxide (H2O2), cardiolipin, and oxidized cardiolipin were also measured. ß-hydroxy acyl-CoA dehydrogenase (ß-HAD) (38%) and citrate synthase (77%) activities were significantly lower, and H2O2 (1.4-fold) and oxidized cardiolipin (1.8-fold) were significantly higher in HIV-infected men. VO2peak (mL/kg FFM/min) was 33% lower in HIV-infected men and was directly related to ß-HAD and citrate synthase activity and inversely related to H2O2 and oxidized cardiolipin. Older HIV-infected men have reduced oxidative enzyme activity and increased oxidative stress compared to age-matched controls. Further research is crucial to determine whether an increase in aerobic capacity by exercise training will be sufficient to restore mitochondrial function in older HIV-infected individuals.

Increased Energy Cost of Mobility in Chronic Stroke.

The purpose of this study was to compare the energy cost of completing mobility-related activities in chronic stroke to the estimated energy cost found in the compendium of physical activities, a resource that estimates and classifies energy cost of various human physical activities. Men (n=18) and women (n=10) with chronic hemiparetic gait (stroke latency: 4 ± 2 years, age: 60.4 ± 1.6 years, BMI: 31.5 ± 1.1 kg/m2) participated in the study. Portable energy cost monitoring (COSMED K4b2) was performed during five mobility activities of varying intensity to determine metabolic equivalents (METs, or oxygen consumption in multiples of resting level) for each activity. The METs achieved during the five activities were compared to the following compendium MET values for: 1) floor sweeping; 2) stepping in place; 3) over-ground walking; 4) lower speed treadmill walking (1.0 mph at 4% incline); and 5) higher speed treadmill walking (2.0 mph at 4% incline). Measurements were obtained for 10 min at rest and 5 minutes during each of the five activities. The energy cost of rest was only 85% of Compendium METS, while mobility-related activities were ~1.25-1.50 fold greater when measured in stroke vs. Compendium METS for all measures (P's<0.05), except floor sweeping, which was similar between groups. These data indicate that MET levels provided in the compendium are not applicable to chronic stroke survivors as they overestimate energy expenditure at rest and underestimate energy expenditure during physical activity, indicating poor efficiency in movement, thus elevating the oxygen cost of completing general daily activities.

Higher Treadmill Training Intensity to Address Functional Aerobic Impairment after Stroke.

BACKGROUND: Peak aerobic capacity (VO2 peak) is severely worsened after disabling stroke, having serious implications for function, metabolism, and ongoing cardiovascular risk. Work from our laboratory and others has previously shown that modest improvements in VO2 peak are possible in stroke participants with aerobic exercise training. The purpose of the current investigation was to test the extent to which greater enhancements in VO2 peak after stroke are possible using a treadmill protocol with far greater emphasis on intensity progression compared with a protocol without such emphasis. METHODS: Using a randomized design, we compared stroke survivors engaged in higher intensity treadmill training (HI-TM, 80% heart rate reserve [HRR]) with those undergoing lower intensity treadmill training (LO-TM, 50% HRR). Measured outcomes were change in VO2 peak, 6-minute walk distance (6MWD), 30-ft walk times (30WT), and 48-hour step counts (48SC). LO-TM participants trained for a longer period of time per session in an effort to approximately match workload/caloric expenditure. Participants were randomized with stratification according to age and baseline walking capacity. RESULTS: HI-TM participants (n = 18) had significantly greater gains in VO2 peak (+34%) than LO-TM participants (n = 16; +5%) across the 6-month intervention period (P = .001, group × time interaction). Conversely, there was no statistical difference between groups in the changes observed for 6MWD, 30WT, or 48SC. CONCLUSIONS: HI-TM is far more effective than LO-TM for improving VO2 peak after disabling stroke. The magnitude of relative improvement for HI-TM was double compared with previous reports from our laboratory with probable clinical significance for this population.

Reduced Resting Metabolic Rate in Adults with Hemiparetic Chronic Stroke.

OBJECTIVE: Resting metabolic rate (RMR) is the component of energy expenditure that explains the largest proportion of total daily energy requirements. Since RMR is determined largely by fat-free mass and a low RMR predicts weight gain in healthy adults, identifying the role of muscle atrophy following stroke on RMR may help identify ways to mitigate the development of obesity post-stroke. METHODS: Thirty-nine stroke survivors with chronic hemiparesis (mean ± SEM: age: 61 ± 1 years, latency from stroke: 107 ± 40 months, BMI: 31 ± 3 kg/m2) underwent DXA scans for measurement of body composition, including total, paretic, and non-paretic leg lean mass and fasted, 30-min indirect calorimetry for measurement of RMR. RESULT: Predicted RMR was calculated by the Mifflin-St Jeor equation, which considers weight, height, and age for both men and women. RMR was 14% lower than predicted (1438 ± 45 vs. 1669 ± 38 kcals/24 hrs; P<0.01). Total (r=0.73, P<0.01), paretic (r=0.72, P<0.01) and non-paretic (r=0.67, P<0.01) leg lean mass predicted RMR. CONCLUSION: These data indicate that muscle atrophy post stroke may lead to a reduced RMR. This substantiates the need to attenuate the loss of lean mass after a stroke to prevent declines in RMR and possible weight gain common post-stroke.

Impact of serum nutritional status on physical function in african american and caucasian stroke survivors.

Background. The purpose of this study is to compare serum nutritional profiles in chronic stroke survivors to a representative sample of US Adults (NHANESIII) and determine whether these serum markers differed by race and impact physical function in stroke. Methods. Fasting serum samples were collected for analysis of lipids, uric acid, and albumin in 145 African American (AA) and 111 Caucasian (C) stroke survivors (age: 60 ± 1 years [mean ± SEM]). A six-minute walk was performed in a subset of stroke survivors (N = 134). Results. Triglycerides were higher and HDL-cholesterol and albumin lower in C than AA women stroke survivors (Ps < 0.05). Uric acid was lower in C than AA stroke survivors (P < 0.05). Compared to NHANESIII, HDL-cholesterol, albumin, and hemoglobin generally were lower (Ps < 0.05) and lipids were more favorable in stroke (Ps < 0.01). Uric acid was related to six-minute walk performance among a subset of stroke survivors (P < 0.05). Conclusion. In stroke, racial differences exist with regard to serum nutritional risk, but these differences are similar to that observed in the general population. Regardless of race, nutritional risk appears elevated above that of the general population with regard to many of the serum markers. As a modifiable biomarker, uric acid should be monitored closely as it may provide insight into the functional risk of stroke survivors.