Multiple propane gas burn rates procedure to determine accuracy and linearity of indirect calorimetry systems: an experimental assessment of a method.

Objective: Indirect calorimetry (IC) systems measure the fractions of expired carbon dioxide (FeCO2), and oxygen (FeO2) recorded at the mouth to estimate whole-body energy production. The fundamental principle of IC relates to the catabolism of high-energy substrates such as carbohydrates and lipids to meet the body's energy needs through the oxidative process, which are reflected in the measured oxygen uptake rates (V̇O2) and carbon dioxide production rates (V̇CO2). Accordingly, it is important to know the accuracy and validity of V̇O2and V̇CO2 measurements when estimating energy production and substrate partitioning for research and clinical purposes. Although several techniques are readily available to assess the accuracy of IC systems at a single point for V̇CO2 and V̇O2, the validity of such procedures is limited when used in testing protocols that incorporate a wide range of energy production (e.g., basal metabolic rate and maximal exercise testing). Accordingly, we built an apparatus that allowed us to manipulate propane burn rates in such a way as to assess the linearity of IC systems. This technical report aimed to assess the accuracy and linearity of three IC systems using our in-house built validation procedure. Approach: A series of trials at different propane burn rates (PBR) (i.e., 200, 300, 400, 500, and 600 mL min-1) were run on three IC systems: Sable, Moxus, and Oxycon Pro. The experimental values for V̇O2 and V̇CO2 measured on the three IC systems were compared to theoretical stoichiometry values. Results: A linear relationship was observed between increasing PBR and measured values for V̇O2and V̇CO2 (99.6%, 99.2%, 94.8% for the Sable, Moxus, and Jaeger IC systems, respectively). In terms of system error, the Jaeger system had significantly (p < 0.001) greater V̇O2(mean difference (M) = -0.057, standard error (SE) = 0.004), and V̇CO2(M = -0.048, SE = 0.002) error compared to either the Sable (V̇O2, M = 0.044, SE = 0.004; V̇CO2, M = 0.024, SE = 0.002) or the Moxus (V̇O2, M = 0.046, SE = 0.004; V̇CO2, M = 0.025, SE = 0.002) IC systems. There were no significant differences between the Sable or Moxus IC systems. Conclusion: The multiple PBR approach permitted the assessment of linearity of IC systems in addition to determining the accuracy of fractions of expired gases.

Practical guidance for firefighter applicants preparing for cardiorespiratory fitness testing: a secondary analysis of self-reported physical activity levels.

Adequate cardiorespiratory fitness is critical for firefighters since an insufficient level of fitness threatens the integrity of their operations and could be dangerous for their lives. In fact, the leading cause of mortality for on-duty firefighters is not injury but sudden cardiac death. Therefore, to mitigate these risks, potential firefighter recruits are often required to perform a graded exercise test to determine their cardiorespiratory fitness as part of the recruitment process. However, there are currently limited data available to prospective firefighters on the amounts and types of exercises needed to be successful in the graded exercise test, commonly known as a V̇O2max test. Physiological parameters for the current secondary analysis were collected on firefighter applicants who performed the graded exercise test where 72% were successful and 28% were unsuccessful to meet the minimum standard set at 42.5 ml kg-1 min-1. Prior to their test, applicants were asked to describe their exercise training routine by indicating the number of minutes per week spent exercising. Activities were then divided into one of two categories: endurance exercise or strength and power exercise training. The total exercise training describes the sum of all activities performed each week. The sum of endurance exercise activities and the sum of strength and power exercise activities were compared between the successful and the unsuccessful groups and results showed that successful applicants had a higher training volume and performed more endurance exercise training as compared to unsuccessful applicants. Therefore, practical recommendations related to exercise training regime are presented for firefighter applicants to embrace as guidance to prepare for their graded exercise test as part of their recruitment process.

Type of self-talk matters: Its effects on perceived exertion, cardiorespiratory, and cortisol responses during an iso-metabolic endurance exercise.

Self-talk is an effective mental training technique that has been shown to facilitate or debilitate an athlete's performance, depending on its valence. Although the effects of self-talk have been supported by observing change in sport performance, little is known about how self-talk can induce physiological changes. Specifically, it is important to understand if the type of self-talk (positive, neutral, or negative) and can influence stress-related parameters, such as perceived exertion, cardiorespiratory, and cortisol responses. The study's objective was therefore to investigate the top-down effect of positive and negative self-talk compared to a dissociative activity during an iso-metabolic running exercise on autonomic regulation of cardiorespiratory function. Twenty-nine well-trained male runners [38 ± 13 years, 177 ± 7 cm and 73 ± 7 kg] volunteered to participate in a randomized-group design study that included a negative self-talk (NST), a positive self-talk, and a dissociative group (DG). First, participants underwent an incremental running test on a treadmill to determine the maximal oxygen uptake (V̇O2max ). Next, participants received a mental training session on self-talk and created three positive and three negative self-talk statements. Finally, participants underwent a 60-min steady-state running exercise on a treadmill at 70% of V̇O2max , during which they were cued at 20-, 35-, and 50-min with their personal self-created positive or negative self-talk statements while the DG listened to a documentary. Cardiorespiratory parameters and rate of perceived exertion (RPE) were recorded throughout the 60-min endurance exercise. In addition, salivary cortisol samples were obtained at waking and after treatment. Although oxygen uptake, carbon dioxide production, RPE, and heart rate significantly changed overtime during the 60-min steady-state running exercise, no significant main treatment effect was found. However, RPE scores, minute ventilation, breathing frequency, and salivary cortisol were significantly higher in the NST group compared to the two other groups. These data suggest that NST [emotion-induced stress, as reflected by elevated cortisol] altered the breathing frequency response. In conclusion, manipulating self-talk alters hormonal response patterns, modulates cardiorespiratory function, and influences perceived exertion.

Normobaric Hypoxia Exposure During Treadmill Aerobic Exercise After Stroke: A Safety and Feasibility Study.

OBJECTIVE: To evaluate the safety and feasibility of performing treadmill aerobic exercise in moderate normobaric hypoxia among chronic hemiparetic stroke survivors. DESIGN: Observational study using convenience sampling. SETTING: Research laboratory in a tertiary rehabilitation hospital. PARTICIPANTS: Chronic hemiparetic stroke survivors who could walk at least 10-m with or without assistance and had no absolute contraindications to exercise testing. INTERVENTION: Participants (three male and four female) were asked to complete three normobaric hypoxia exposure protocols within a single session. First, they were passively exposed to normobaric hypoxia through gradual reductions in the fraction of inspired oxygen (FIO2 = 20.9, 17.0, and 15.0%) while seated (5-min at each level of FIO2). Participants were then exposed to the same reductions in FIO2 during constant-load exercise performed on a treadmill at 40% of heart rate reserve. Finally, participants completed 20-min of exercise while intermittently exposed to moderate normobaric hypoxia (5 × 2-min at FIO2 = 15.0%) interspaced with 2-min normoxia intervals (FIO2 = 20.9%). OUTCOME MEASURES: The primary outcome was occurrence of adverse events, which included standardized criteria for terminating exercise testing, blood oxygen saturation (SpO2) <80%, or acute mountain sickness score >2. The increased cardiovascular strain imposed by normobaric hypoxia exposure at rest and during exercise was evaluated by changes in SpO2, heart rate (HR), blood pressure, and rating of perceived exertion (RPE). RESULTS: One participant reported mild symptoms of nausea during exercise in normobaric hypoxia and discontinued participation. No other adverse events were recorded. Intermittent normobaric hypoxia exposure was associated with reduced SpO2 (MD = -7.4%, CI: -9.8 to -5.0) and increased HR (MD = 8.2, CI: 4.6 to 11.7) compared to intervals while breathing typical room air throughout the 20-min constant-load exercise period. The increase in HR was associated with a 10% increase in relative effort. However, reducing FIO2 had little effect on blood pressure and RPE measurements. CONCLUSION: Moderate normobaric hypoxia appeared to be a safe and feasible method to increase the cardiovascular strain of submaximal exercise in chronic hemiparetic stroke survivors. Future studies evaluating the effects of pairing normobaric hypoxia exposure with existing therapies on secondary prevention and functional recovery are warranted.

Task-Oriented Circuit Training as an Alternative to Ergometer-Type Aerobic Exercise Training after Stroke.

Moderate-intensity aerobic exercise training is an important treatment strategy to enhance functional recovery and decrease cardiometabolic risk factors after stroke. However, stroke related impairments limit access to ergometer-type exercise. The aims of the current study were (1) to evaluate whether our task-oriented circuit training protocol (intermittent functional training; IFT) could be used to sustain moderate-intensity aerobic workloads over a 10-week intervention period, and (2) to investigate its preliminary effects on cardiorespiratory fitness and metabolic profiles compared to constant-load ergometer-type exercise (CET). Forty chronic hemiparetic stroke survivors were randomized to receive 30 sessions of IFT or CET over ten weeks. Similar proportions of participants were randomized to IFT (7/19) and CET (9/18) sustained workloads associated with moderate-intensity aerobic exercise over the study period (p = 0.515). However, CET was associated with more substantial changes in maximal oxygen uptake (MD = 2.79 mL min-1 kg-1 CI: 0.84 to 4.74) compared to IFT (MD = 0.62 mL min-1 kg-1 CI: -0.38 to 1.62). Pre to post changes in C-reactive protein (-0.9 mg/L; p =0.017), short-term glycemia (+14.7 mol/L; p = 0.026), and resting whole-body carbohydrate oxidation (+24.2 mg min-1; p = 0.046) were observed when considering both groups together. Accordingly, IFT can replicate the aerobic intensities sustained during traditional ergometer-type exercise training. More work is needed to evaluate the dose-response effects of such task-oriented circuit training protocols on secondary prevention targets across the continuum of stroke recovery.

Exercise-Induced Brain Excitability Changes in Progressive Multiple Sclerosis: A Pilot Study.

BACKGROUND AND PURPOSE: Even a single bout of aerobic exercise (AE) enhances corticospinal excitability (CSE), a biomarker of neuroplasticity. Because neurodegeneration limits capacity for neuroplasticity, it is not clear whether AE would induce CSE changes in people with progressive multiple sclerosis (MS). METHODS: People with progressive MS (n = 10) requiring ambulatory assistive devices completed a graded maximal exercise test. Dual-energy x-ray absorptiometry was used to quantify body fat and lean mass. Before and following one 40-minute AE session using body weight-supported (<10% support) treadmill at moderate intensity, CSE was measured using transcranial magnetic stimulation. Variables included resting and active motor thresholds, motor evoked potential (MEP) amplitudes, recruitment curves, and length of the cortical silent period (CSP). RESULTS: Aerobic exercise reduced inhibition (shorter CSP) and increased excitation (increased MEP amplitude) only in the hemisphere corresponding to the stronger hand. Controlling for age, higher fitness and lower body fat significantly predicted exercise-induced reduction in resting motor threshold (ΔR = +0.458, P = 0.046) and CSP (ΔR = +0.568, P = 0.030), respectively. DISCUSSION AND CONCLUSIONS: Despite high levels of disability, capacity for exercise-induced neuroplasticity was retained among people with progressive MS. The hemisphere contralateral to the weaker hand was resistant to exercise-induced CSE changes, suggesting less neuroplastic potential. Lower fitness and higher body fat were associated with diminished exercise-induced CSE benefits, suggesting that therapists should consider interventions aimed at improving fitness and combating sedentarism to ultimately enhance the benefits of exercise on the brain.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A302).

Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study.

BACKGROUND: Aerobic training has the potential to restore function, stimulate brain repair, and reduce inflammation in people with Multiple Sclerosis (MS). However, disability, fatigue, and heat sensitivity are major barriers to exercise for people with MS. We aimed to determine the feasibility of conducting vigorous harness-supported treadmill training in a room cooled to 16 °C (10 weeks; 3times/week) and examine the longer-term effects on markers of function, brain repair, and inflammation among those using ambulatory aids. METHODS: Ten participants (9 females) aged 29 to 74 years with an Expanded Disability Status Scale ranging from 6 to 7 underwent training (40 to 65% heart rate reserve) starting at 80% self-selected walking speed. Feasibility of conducting vigorous training was assessed using a checklist, which included attendance rates, number of missed appointments, reasons for not attending, adverse events, safety hazards during training, reasons for dropout, tolerance to training load, subjective reporting of symptom worsening during and after exercise, and physiological responses to exercise. Functional outcomes were assessed before, after, and 3 months after training. Walking ability was measured using Timed 25 Foot Walk test and on an instrumented walkway at both fast and self-selected speeds. Fatigue was measured using fatigue/energy/vitality sub-scale of 36-Item Short-Form (SF-36) Health Survey, Fatigue Severity Scale, modified Fatigue Impact Scale. Aerobic fitness (maximal oxygen consumption) was measured using maximal graded exercise test (GXT). Quality-of-life was measured using SF-36 Health Survey. Serum levels of neurotrophin (brain-derived neurotrophic factor) and cytokine (interleukin-6) were assessed before and after GXT. RESULTS: Eight of the ten participants completed training (attendance rates ≥ 80%). No adverse events were observed. Fast walking speed (cm/s), gait quality (double-support (%)) while walking at self-selected speed, fatigue (modified Fatigue Impact Scale), fitness (maximal workload achieved during GXT), and quality-of-life (physical functioning sub-scale of SF-36) improved significantly after training, and improvements were sustained after 3-months. Improvements in fitness (maximal respiratory exchange ratio and maximal oxygen consumption during GXT) were associated with increased brain-derived neurotrophic factor and decreased interleukin-6. CONCLUSION: Vigorous cool room training is feasible and can potentially improve walking, fatigue, fitness, and quality-of-life among people with moderate to severe MS-related disability. TRIAL REGISTRATION: The study was approved by the Newfoundland and Labrador Health Research Ethics Board (reference number: 2018.088) on 11/07/2018 prior to the enrollment of first participant (retrospectively registered at ClinicalTrials.gov: NCT04066972. Registered on 26 August 2019.

Prior Band-Resisted Squat Jumps Improves Running and Neuromuscular Performance in Middle-Distance Runners.

Post-activation potentiation (PAP) conditioning has been reported to increase performance. Most research has examined PAP effects on strength/power activities, whereas the effects on endurance sports are understudied. The aim of this study was to characterize PAP conditioning stimulus effects on a subsequent 5x1 km running trial. A randomized, within subjects, repeated measures study utilized 12 male, endurance-trained athletes, who performed a full warm-up, conditioning exercise intervention (4x5 repetition maximum band-resisted squat jumps) or a control condition prior to a 5x1 km time trial run. Tests were conducted immediately prior to the intervention, after each kilometer, immediately following the 5x1 km run, and at seven and ten minutes post 5 km run. Measures included the interpolated twitch technique (ITT), evoked contractile properties, maximum voluntary isometric contractions (MVIC) plantar flexor force, drop jump, rating of perceived exertion, and heart rate. The PAP stimulus reduced the time to complete the run (3.6%; p = 0.07, d = 0.51), and decreased the time to complete kilometer one (8%; d = 1.08, p = 0.014). Jump height (p = 0.02; 9.2%) and reactive strength index (p = 0.035; 16%) increased with PAP. F100 (force produced in the first 100ms of the MVIC) and MVIC force with PAP increased at kilometers 3 (p = 0.04, d=0.84), 4 (p = 0.034, d = 0.29), and 7min post-run (p = 0.03, d = 0.60). Voluntary activation (ITT) increased at 7min post-run (p = 0.04, d = 0.59) with PAP, yet decreased at 7min post-run in the control condition (p = 0.03, d = 0.36). A prior band-resisted squat protocol decreased running time and improved neuromuscular properties in endurance athletes running 5x1 km.

Oxygen Cost During Mobility Tasks and Its Relationship to Fatigue in Progressive Multiple Sclerosis.

OBJECTIVE: To compare the oxygen costs of mobility tasks between individuals with progressive multiple sclerosis (MS) using walking aids and matched controls and to determine whether oxygen cost predicted fatigue. DESIGN: Cross-sectional descriptive. SETTING: A rehabilitation research laboratory. PARTICIPANTS: A total of 14 adults with progressive MS (mean age ± SD [y], 54.07±8.46) using walking aids and 8 age- and sex-matched controls without MS (N=22). INTERVENTIONS: Participants performed 5 mobility tasks (rolling in bed, lying to sitting, sitting to standing, walking, climbing steps) wearing a portable metabolic cart. MAIN OUTCOME MEASURES: Oxygen consumption (V˙o2) during mobility tasks, maximal V˙o2 during graded maximal exercise test, perceived exertion, and task-induced fatigue were measured on a visual analog scale before and after mobility tasks. RESULTS: People with progressive MS had significantly higher oxygen cost in all tasks compared to controls (P<.05): climbing steps (3.60 times more in MS), rolling in bed (3.53), walking (3.10), lying to sitting (2.50), and sitting to standing (1.82). There was a strong, positive correlation between task-induced fatigue and oxygen cost of walking, (ρ [13]=0.626, P=.022). CONCLUSIONS: People with progressive MS used 2.81 times more energy on average for mobility tasks compared to controls. People with progressive MS experienced accumulation of oxygen cost, fatigue, and exertion when repeating tasks and higher oxygen cost during walking was related to greater perception of fatigue. Our findings suggest that rehabilitation interventions that increase endurance during functional tasks could help reduce fatigue in people with progressive MS who use walking aids.

Synergistic Benefits of Combined Aerobic and Cognitive Training on Fluid Intelligence and the Role of IGF-1 in Chronic Stroke.

BACKGROUND: Paired exercise and cognitive training have the potential to enhance cognition by "priming" the brain and upregulating neurotrophins. METHODS: Two-site randomized controlled trial. Fifty-two patients >6 months poststroke with concerns about cognitive impairment trained 50 to 70 minutes, 3× week for 10 weeks with 12-week follow-up. Participants were randomized to 1 of 2 physical interventions: Aerobic (>60% VO2peak using <10% body weight-supported treadmill) or Activity (range of movement and functional tasks). Exercise was paired with 1 of 2 cognitive interventions (computerized dual working memory training [COG] or control computer games [Games]). The primary outcome for the 4 groups (Aerobic + COG, Aerobic + Games, Activity + COG, and Activity + Games) was fluid intelligence measured using Raven's Progressive Matrices Test administered at baseline, posttraining, and 3-month follow-up. Serum neurotrophins collected at one site (N = 30) included brain-derived neurotrophic factor (BDNF) at rest (BDNFresting) and after a graded exercise test (BDNFresponse) and insulin-like growth factor-1 at the same timepoints (IGF-1rest, IGF-1response). RESULTS: At follow-up, fluid intelligence scores significantly improved compared to baseline in the Aerobic + COG and Activity + COG groups; however, only the Aerobic + COG group was significantly different (+47.8%) from control (Activity + Games -8.5%). Greater IGF-1response at baseline predicted 40% of the variance in cognitive improvement. There was no effect of the interventions on BDNFresting or BDNFresponse; nor was BDNF predictive of the outcome. CONCLUSIONS: Aerobic exercise combined with cognitive training improved fluid intelligence by almost 50% in patients >6 months poststroke. Participants with more robust improvements in cognition were able to upregulate higher levels of serum IGF-1 suggesting that this neurotrophin may be involved in behaviorally induced plasticity.

The Investigation into the Toxic Potential of Iron Oxide Nanoparticles Utilizing Rat Pheochromocytoma and Human Neural Stem Cells.

Magnetic iron oxide (Magnetite, Fe3O4) nanoparticles are widely utilized in magnetic resonance imaging (MRI) and drug delivery applications due to their superparamagnetism. Surface coatings are often employed to change the properties of the magnetite nanoparticles or to modulate their biological responses. In this study, magnetite nanoparticles were fabricated through hydrothermal synthesis. Hydrophobicity is often increased by surface modification with oleic acid. In this study, however, hydrophobicity was introduced through surface modification with n-octyltriethoxysilane. Both the uncoated (hydrophilic) and coated (hydrophobic) individual nanoparticle sizes measured below 20 nm in diameter, a size range in which magnetite nanoparticles exhibit superparamagnetism. Both types of nanoparticles formed aggregates which were characterized by SEM, TEM, and dynamic light scattering (DLS). The coating process significantly increased both individual particle diameter and aggregate sizes. We tested the neurotoxicity of newly synthesized nanoparticles with two mammalian cell lines, PC12 (rat pheochromocytoma) and ReNcell VM (human neural stem cells). Significant differences were observed in cytotoxicity profiles, which suggests that the cell type (rodent versus human) or the presence of serum matters for nanoparticle toxicology studies. Differences in nanoparticle associations/uptake between the two cell types were observed with Prussian Blue staining. Finally, safe concentrations which did not significantly affect neuronal differentiation profiles were identified for further development of the nanoparticles.

Prolonged cortical silent period is related to poor fitness and fatigue, but not tumor necrosis factor, in Multiple Sclerosis.

OBJECTIVE: Poor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown. METHODS: MS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP). RESULTS: Sixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable. CONCLUSION: Low fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue. SIGNIFICANCE: MS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks.

Serum levels of insulin-like growth factor-1 and brain-derived neurotrophic factor as potential recovery biomarkers in stroke.

OBJECTIVES: Our objectives were: 1) to determine whether maximal aerobic exercise increased serum neurotrophins in chronic stroke and 2) to determine the factors that predict resting and exercise-dependent levels. METHODS: We investigated the potential predictors of resting and exercise-dependent serum insulin-like growth factor-1 and brain-derived neurotrophic factor among 35 chronic stroke patients. Predictors from three domains (demographic, disease burden, and cardiometabolic) were entered into 4 separate stepwise linear regression models with outcome variables: resting insulin-like growth factor, resting brain-derived neurotrophic factor, exercise-dependent change in insulin-like growth factor, and exercise-dependent change brain-derived neurotrophic factor. RESULTS: Insulin-like growth factor decreased after exercise (p = 0.001) while brain-derived neurotrophic factor did not change (p = 0.38). Greater lower extremity impairment predicted higher resting brain-derived neurotrophic factor (p = 0.004, r2 = 0.23). Higher fluid intelligence predicted greater brain-derived neurotrophic factor response to exercise (p = 0.01, r2 = 0.18). There were no significant predictors of resting or percent change insulin-like growth factor-1. DISCUSSION: Biomarkers have the potential to characterize an individual's potential for recovery from stroke. Neurotrophins such as insulin-like growth factor-1 and brain-derived neurotrophic factor are thought to be important in neurorehabilitation; however, the factors that modulate these biomarkers are not well understood. Resting brain-derived neurotrophic factor and percent change in brain-derived neurotrophic factor were related to physical and cognitive recovery in chronic stroke, albeit weakly. Insulin-like growth factor-1 was not an informative biomarker among chronic stroke patients. The novel finding that fluid intelligence positively correlated with exercise-induced change in brain-derived neurotrophic factor warrants further research.

Asymmetry of Brain Excitability: A New Biomarker that Predicts Objective and Subjective Symptoms in Multiple Sclerosis.

OBJECTIVES: Investigate whether asymmetrical corticospinal excitability exists in Multiple Sclerosis (MS) and its association with MS symptoms. METHODS: Bilateral resting and active motor thresholds (RMT, AMT) were gathered using transcranial magnetic stimulation among 82 MS patients. Corticospinal excitability (CSE) asymmetry was expressed as the ratio between weaker and stronger sides' RMT and AMT. Stronger and weaker side was determined by pinch and grip strength. We examined whether CSE asymmetry predicted symptoms. RESULTS: AMT asymmetry ratio revealed atypical CSE asymmetry whereby the hemisphere associated with the weaker hand was more excitable in early MS. After controlling for MS disease demographics, shifting of CSE asymmetry towards greater excitability in the stronger side significantly predicted more severe symptoms including Expanded Disease Severity Scale, nine-hole peg test, cognitive processing speed, walking speed, heat sensitivity, fatigue, and subjective impact of MS. CONCLUSION: CSE asymmetry significantly predicted the severity of MS-related physical and objective cognitive symptoms. The phenomenon may be related to neuroinflammation-mediated hyperexcitability. Shifting of asymmetry toward less excitability on the weaker side may suggest the onset of a more neurodegenerative phase of the disease. SIGNIFICANCE: Shifting of hemispheric excitability, detected using a CSE asymmetry ratio, may be a useful biomarker to track disease progression and understand the benefits of treatments.

A Bout of High Intensity Interval Training Lengthened Nerve Conduction Latency to the Non-exercised Affected Limb in Chronic Stroke.

Objective: Evaluate intensity-dependent effects of a single bout of high intensity interval training (HIIT) compared to moderate intensity constant-load exercise (MICE) on corticospinal excitability (CSE) and effects on upper limb performance in chronic stroke. Design: Randomized cross-over trial. Setting: Research laboratory in a tertiary rehabilitation hospital. Participants: Convenience sample of 12 chronic stroke survivors. Outcome measures: Bilateral CSE measures of intracortical inhibition and facilitation, motor thresholds, and motor evoked potential (MEP) latency using transcranial magnetic stimulation. Upper limb functional measures of dexterity (Box and Blocks Test) and strength (pinch and grip strength). Results: Twelve (10 males; 62.50 ± 9.0 years old) chronic stroke (26.70 ± 23.0 months) survivors with moderate level of residual impairment participated. MEP latency from the ipsilesional hemisphere was lengthened after HIIT (pre: 24.27 ± 1.8 ms, and post: 25.04 ± 1.8 ms, p = 0.01) but not MICE (pre: 25.49 ± 1.10 ms, and post: 25.28 ± 1.0 ms, p = 0.44). There were no significant changes in motor thresholds, intracortical inhibition or facilitation. Pinch strength of the affected hand decreased after MICE (pre: 8.96 ± 1.9 kg vs. post: 8.40 ± 2.0 kg, p = 0.02) but not after HIIT (pre: 8.83 ± 2.0 kg vs. post: 8.65 ± 2.2 kg, p = 0.29). Regardless of type of aerobic exercise, higher total energy expenditure was associated with greater increases in pinch strength in the affected hand after exercise (R2 = 0.31, p = 0.04) and decreases in pinch strength of the less affected hand (R2 = 0.26 p = 0.02). Conclusion: A single bout of HIIT resulted in lengthened nerve conduction latency in the affected hand that was not engaged in the exercise. Longer latency could be related to the cross-over effects of fatiguing exercise or to reduced hand spasticity. Somewhat counterintuitively, pinch strength of the affected hand decreased after MICE but not HIIT. Regardless of the structure of exercise, higher energy expended was associated with pinch strength gains in the affected hand and strength losses in the less affected hand. Since aerobic exercise has acute effects on MEP latency and hand strength, it could be paired with upper limb training to potentiate beneficial effects.

Excessive sedentary time during in-patient stroke rehabilitation.

Background and Purpose Previous research suggests that patients receiving inpatient stroke rehabilitation are sedentary although there is little data to confirm this supposition within the Canadian healthcare system. The purpose of this cross-sectional study was to observe two weeks of inpatient rehabilitation in a tertiary stroke center to determine patients' activity levels and sedentary time. Methods Heart rate (HR) and accelerometer data were measured using an Actiheart monitor for seven consecutive days, 24 h/day, on the second week and the last week of admission. Participants or their proxies completed a daily logbook. Metabolic equivalent (MET) values were calculated and time with MET < 1.5 was considered sedentary. The relationship between patient factors (disability, mood, and social support) and activity levels and sedentary time were analyzed. Results Participants (n = 19; 12 males) spent 10 h sleeping and 4 h resting each day, with 86.9% of their waking hours sedentary. They received on average 8.5 task-specific therapy sessions; substantially lower than the 15 h/week recommended in best practice guidelines. During therapy, 61.6% of physical therapy and 76.8% of occupational therapy was spent sedentary. Participants increased their HR about 15 beats from baseline during physical therapy and 8 beats during occupational therapy. There was no relationship between sedentary time or activity levels and patient factors. Discussion Despite calls for highly intensive stroke rehabilitation, there was excessive sedentary time and therapy sessions were less frequent and of lower intensity than recommended levels. Conclusions In this sample of people attending inpatient stroke rehabilitation, institutional structure of rehabilitation rather than patient-related factors contributed to sedentary time.

Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing.

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.

Intensifying Functional Task Practice to Meet Aerobic Training Guidelines in Stroke Survivors.

Objective: To determine whether stroke survivors could maintain workloads during functional task practice that can reach moderate levels of cardiometabolic stress (i.e., ≥40% oxygen uptake reserve ([Formula: see text]O2R) for ≥20 min) without the use of ergometer-based exercise. Design: Cross-sectional study using convenience sampling. Setting: Research laboratory in a tertiary rehabilitation hospital. Participants: Chronic hemiparetic stroke survivors (>6-months) who could provide consent and walk with or without assistance. Intervention: A single bout of intermittent functional training (IFT). The IFT protocol lasted 30 min and involved performing impairment specific multi-joint task-oriented movements structured into circuits lasting ~3 min and allowing 30-45 s recovery between circuits. The aim was to achieve an average heart rate (HR) 30-50 beats above resting without using traditional ergometer-based aerobic exercise. Outcome measures: Attainment of indicators for moderate intensity aerobic exercise. Oxygen uptake ([Formula: see text]O2), carbon dioxide production ([Formula: see text]CO2), and HR were recorded throughout the 30 min IFT protocol. Values were reported as percentage of [Formula: see text]O2R, HR reserve (HRR) and HRR calculated from predicted maximum HR (HRRpred), which were determined from a prior maximal graded exercise test. Results: Ten (3-female) chronic (38 ± 33 months) stroke survivors (70% ischemic) with significant residual impairments (NIHSS: 3 ± 2) and a high prevalence of comorbid conditions (80% ≥ 1) participated. IFT significantly increased all measures of exercise intensity compared to resting levels: [Formula: see text]O2 (Δ 820 ± 290 ml min-1, p < 0.001), HR (Δ 42 ± 14 bpm, p < 0.001), and energy expenditure (EE; Δ 4.0 ± 1.4 kcal min-1, p < 0.001). Also, mean values for percentage of [Formula: see text]O2R (62 ± 19), HRR (55 ± 14), and HRRpred (52 ± 18) were significantly higher than the minimum threshold (40%) indicating achievement of moderate intensity aerobic exercise (p = 0.004, 0.016, and 0.043, respectively). Conclusion: Sufficient workloads to achieve moderate levels of cardiometabolic stress can be maintained in chronic stroke survivors using impairment-focused functional movements that are not dependent on ergometers or other specialized equipment.

Acute Normobaric Hypoxia Increases Post-exercise Lipid Oxidation in Healthy Males.

The primary objective of the current study was to determine the effect of moderate normobaric hypoxia exposure during constant load cycling on post-exercise energy metabolism recorded in normoxia. Indirect calorimetry was used to examine whole body substrate oxidation before, during, 40-60 min post, and 22 h after performing 60 min of cycling exercise at two different fractions of inspired oxygen (FIO2): (i) FIO2 = 0.2091 (normoxia) and (ii) FIO2 = 0.15 (hypoxia). Seven active healthy male participants (26 ± 4 years of age) completed both experimental trials in randomized order with a 7-day washout period to avoid carryover effects between conditions. Resting energy expenditure was initially elevated following cycling exercise in normoxia and hypoxia (Δ 0.14 ± 0.05, kcal min-1, p = 0.037; Δ 0.19 ± 0.03 kcal min-1, p < 0.001, respectively), but returned to baseline levels the next morning in both conditions. Although, the same absolute workload was used in both environmental conditions (157 ± 10 W), a shift in resting substrate oxidation occurred after exercise performed in hypoxia while post-exercise measurements were similar to baseline after cycling exercise in normoxia. The additional metabolic stress of hypoxia exposure was sufficient to increase the rate of lipid oxidation (Δ 42 ± 11 mg min-1, p = 0.019) and tended to suppress carbohydrate oxidation (Δ -55 ± 26 mg min-1, p = 0.076) 40-60 min post-exercise. This shift in substrate oxidation persisted the next morning, where lipid oxidation remained elevated (Δ 9 ± 3 mg min-1, p = 0.0357) and carbohydrate oxidation was suppressed (Δ -22 ± 6 mg min-1, p = 0.019). In conclusion, prior exercise performed under moderate normobaric hypoxia alters post-exercise energy metabolism. This is an important consideration when evaluating the metabolic consequences of hypoxia exposure during prolonged exercise, and future studies should evaluate its role in the beneficial effects of intermittent hypoxia training observed in persons with obesity and insulin resistance.

Environmental temperature and exercise modality independently impact central and muscle fatigue among people with multiple sclerosis.

BACKGROUND: Heat sensitivity and fatigue limit the ability of multiple sclerosis patients to participate in exercise. OBJECTIVE: The purpose of this study was to determine the optimal aerobic exercise parameters (environmental temperature and exercise modality) to limit exercise-induced central and muscle fatigue among people with multiple sclerosis. METHODS: Fourteen people with multiple sclerosis with varying levels of disability completed four randomized exercise sessions at 65% of the maximal volume of oxygen: body-weight supported treadmill cool (16°C), body-weight supported treadmill room (21°C), total-body recumbent stepper cool and total-body recumbent stepper room. Maximum voluntary contraction, electromyography, and evoked contractile properties were collected from the more affected plantar flexors along with subjective levels of fatigue, body temperature and perceived level of exertion. RESULTS: Exercise in cooler room temperature increased maximum voluntary contraction force (p = 0.010) and stabilized body temperature (p = 0.011) compared to standard room temperature. People with multiple sclerosis experienced greater peak twitch torque (p = 0.047), shorter time to peak twitch (p = 0.035) and a longer half relaxation time (p = 0.046) after total-body recumbent stepper suggestive of less muscle fatigue. CONCLUSION: Cooling the exercise environment limits the negative effects of central fatigue during aerobic exercise and using total-body recumbent stepper (work distributed among four limbs) rather than body-weight supported treadmill lessens muscular fatigue. Therapists can titrate these two variables to help people with multiple sclerosis achieve sufficient exercise workloads.