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The purpose of this article is to highlight the importance of considering sleep-disordered breathing (SDB) as a potential confounder to rehabilitation research interventions in spinal cord injury (SCI). SDB is highly prevalent in SCI, with increased prevalence in individuals with higher and more severe lesions, and the criterion standard treatment with continuous positive airway pressure remains problematic. Despite its high prevalence, SDB is often untested and untreated in individuals with SCI. In individuals without SCI, SDB is known to negatively affect physical function and many of the physiological systems that negatively affect physical rehabilitation in SCI. Thus, owing to the high prevalence, under testing, low treatment adherence, and known negative effect on the physical function, it is contended that underdiagnosed SDB in SCI may be confounding physical rehabilitation research studies in individuals with SCI. Studies investigating the effect of treating SDB and its effect on physical rehabilitation in SCI were unable to be located. Thus, studies investigating the likely integrated relationship among physical rehabilitation, SDB, and proper treatment of SDB in SCI are needed. Owing to rapid growth in both sleep medicine and physical rehabilitation intervention research in SCI, the authors contend it is the appropriate time to begin the conversations and collaborations between these fields. We discuss a general overview of SDB and physical training modalities, as well as how SDB could be affecting these studies.

The body of research on exercise and physical activity among persons with multiple sclerosis(MS) has expanded rapidly in quantity, but not necessarily quality, over the past 20+ years. There is evidence for beneficial effects of exercise and physical activity on immune cells and neurotrophic factors, brain structure and function, walking and cognitive performance, fatigue, depression, and pain, and quality of life among persons with MS. Nevertheless, there is heterogeneity in the outcomes of exercise and physical activity, and a recognition of substantial challenges for improving the effectiveness of those behaviors in MS. To move the field forward, members of the National MS Society physical wellness research working-group pooled collective experiences for identifying challenges, logistic complexities, and opportunities for researchers in designing and conducting interventions of exercise and physical activity among persons with MS. We examined the scope of our experiences and identified collective "lessons learned" regarding the behaviors themselves; study design features and stage of research; study setting, safety, and sample selection; and implementation of randomized controlled trials(RCTs) and treatment fidelity. This paper provides a resource that can inform researchers, particularly new investigators or established investigators transitioning into MS, on conducting high-quality RCTs on exercise and physical activity in MS.

The bone vascular system is important, yet evaluation of bone hemodynamics is difficult and expensive. This study evaluated the utility and reliability of near-infrared spectroscopy (NIRS), a portable and relatively inexpensive device, in measuring tibial hemodynamics and metabolic rate. Eleven participants were tested twice using post-occlusive reactive hyperemia technique with the NIRS probes placed on the tibia and the medial gastrocnemius (MG) muscle. Measurements were made at rest and after 2 levels of plantarflexion exercise. The difference between oxygenated and deoxygenated hemoglobin signal could be reliably measured with small coefficients of variation (CV; range 5.7–9.8%) and high intraclass correlation coefficients (ICC; range 0.73–0.91). Deoxygenated hemoglobin rate of change, a potential marker for bone metabolism, also showed good reliability (CV range 7.5–9.8%, ICC range 0.90–0.93). The tibia was characterized with a much slower metabolic rate compared with MG (p < 0.001). While exercise significantly increased MG metabolic rate in a dose-dependent manner (all p < 0.05), no changes were observed for the tibia after exercise compared with rest (all p > 0.05). NIRS is a suitable tool for monitoring hemodynamics and metabolism in the tibia. However, the local muscle exercise protocol utilized in the current study did not influence bone hemodynamics or metabolic rate. Novelty: NIRS can be used to monitor tibial hemodynamics and metabolism with good reliability. Short-duration local muscle exercise increased metabolic rate in muscle but not in bone. High level of loading and exercise volume may be needed to elicit measurable metabolic changes in bone.

Near-infrared spectroscopy (NIRS) has become an increasingly valuable tool to monitor tissue oxygenation (Toxy) in vivo. Observations of changes in the absorption of light with Toxy have been recognized as early as 1876, leading to a milestone NIRS paper by Jobsis in 1977. Changes in the absorption and scatting of light in the 700–850-nm range has been successfully used to evaluate Toxy. The most practical devices use continuous-wave light providing relative values of Toxy. Phase-modulated or pulsed light can monitor both absorption and scattering providing more accurate signals. NIRS provides excellent time resolution (~ 10 Hz), and multiple source–detector pairs can be used to provide low-resolution imaging. NIRS has been applied to a wide range of populations. Continued development of NIRS devices in terms of lower cost, better detection of both absorption and scattering, and smaller size will lead to a promising future for NIRS studies.

Background:Exercise can improve muscle function and mobility in people with multiple sclerosis (MS). However, the effects of exercise training on skeletal muscle oxidative capacity and endurance in people with MS remain unclear, and few studies have evaluated muscle plasticity in people with MS who have moderate-to-severe disability. The present study evaluated the effects of treadmill training on muscle oxidative capacity and muscle endurance and examined the relationship to walking function in people with MS who have moderate-to-severe disability.Methods:Six adults (mean ± SD age, 50 ± 4.9 years) with MS (Expanded Disability Status Scale score, 6.0–6.5) performed treadmill training for 24 minutes approximately twice per week for approximately 8 weeks (16 sessions total) using an antigravity treadmill system. The following measures were taken before and after the intervention phase: muscle oxidative capacity in the medial gastrocnemius using near-infrared spectroscopy after 15 to 20 seconds of electrical stimulation; muscle endurance in the medial gastrocnemius using accelerometer-based mechanomyography during 9 minutes of twitch electrical stimulation in three stages (3 minutes per stage) of increasing frequency (2, 4, and 6 Hz); and walking function using the 2-Minute Walk Test.Results:Mean ± SD muscle oxidative capacity increased from 0.64 ± 0.19 min−1 to 1.08 ± 0.52 min−1 (68.2%). Mean ± SD muscle endurance increased from 80.9% ± 15.2% to 91.5% ± 4.8% at 2 Hz, from 56.3% ± 20.1% to 76.6% ± 15.8% at 4 Hz, and from 29.2% ± 13.1% to 53.9% ± 19.4% at 6 Hz of stimulation in the gastrocnemius. There were no significant improvements in walking function.Conclusions:Treadmill training can improve muscle oxidative capacity and endurance in people with MS who have moderate-to-severe levels of disability.

Aim: Few studies have addressed impact of participation in exercise programs on caregivers or family members of individuals with disabilities.Purpose: To evaluate the impact of interaction rich wel...

Background Non‐invasive determination of mitochondrial capacity via near infrared spectroscopy (NIRS) typically involves voluntary exercise of a single muscle group followed by as many as 26 brief ischemic cuff occlusions to determine a single recovery rate constant (k). Purpose To determine the within‐ and between‐visit repeatability of a shortened bilateral NIRS protocol, and to establish the feasibility of hamstring k measurements. Methods Sixteen young (eight women, eight men; 22 ± 3 years) active adults underwent a bilateral electrical stimulation protocol in which multiple (n = 4) measurements of k for the vastus lateralis (VL) and medial hamstring (MH) muscles were determined on two visits. Repeatability (CV% and intraclass correlations, ICC) and equivalency across visits were assessed for both muscles. Results Mean k values in the VL were consistent with published values and within‐visit ICCs were moderately high for both muscles in both sexes. In men, average k values on visit 2 were within 1% (VL muscle) and 5% (MH muscle) of the values on visit 1 (all p > 0.78). In women, average k values were 10%–15% lower on visit 2 (p = 0.01 and p = 0.15 for MH and VL) with the largest between‐visit differences in a subset of participants with the most days between visits. Conclusions This bilateral NIRS protocol is time efficient and provides valid estimates of k in both sexes and muscle groups with acceptable within‐visit repeatability. Lower than expected between‐visit repeatability in some participants reinforces the need for further investigation of this newly developed protocol to identify and control for experimental and behavioral sources of variation., We developed and tested the reliability of a novel bilateral near infrared spectroscopy protocol to estimate mitochondrial capacity (k) in the vastus lateralis and hamstring muscles of active younger men and women. Within‐visit intraclass correlations were moderately high, but between‐visit repeatability of k in these muscles was lower than expected in a subset of women. Bilateral estimates of k are feasible and time efficient even in the hamstring muscles, but further studies employing this protocol will be needed to identify sources of variation between days.

Introduction: Parkinson's disease (PD) is associated with loss of motor control and difficulty exercising. This study measured skeletal muscle mitochondrial capacity and endurance in individuals with and without PD using novel non-invasive methods. We hypothesized that individuals with PD will have decreased mitochondrial capacity, reduced oxygen recovery, and decreased endurance compared to controls. Methods: Eight participants with PD and nine healthy controls were tested. Mitochondrial capacity was measured as the rate of recovery of muscle metabolism after electrical stimulation using near-infrared spectroscopy (NIRS) and repeated short arterial occlusions. Oxygen recovery was measured as the half time of recovery of oxygen levels after 5 minutes of ischemia. Muscle endurance was determined from changes in twitch contraction acceleration during electrical stimulation at 2, 4, and 6 Hz. Results: Mitochondrial capacity was lower in individuals with PD compared to controls (1.5±0.1min-1 vs. 1.7±0.1min-1, p=0.02). Individuals with PD had slower oxygen recovery after ischemia compared to controls (8.9±2.3s vs. 5.4±0.8s, p=0.01). Endurance was not different between groups at 6 Hz (PD vs controls: 58±23% vs. 69±16%, p=0.34). The effect sizes for mitochondrial capacity and oxygen recovery were large (Cohen's d >0.8). The Cohen's d for endurance was 1.11. Conclusion: Individuals with PD had slight impairments in mitochondrial capacity and blood flow but did not have reduced muscle endurance. While our study suggests that muscle metabolic dysfunction may play a minor role in exercise intolerance in people with PD, it demonstrates the use of noninvasive technologies to evaluate muscle function in people with neurological disorders.

Background/Purpose: Multiple sclerosis (MS) is a progressive neurological disease that results in increased fatigue, decreased muscle function, and impaired gait and balance. The purpose of this study was to evaluate the relationship between lower leg muscle function and changes in gait and balance immediately and 20 minutes after 6mins walk-induced fatigue. Methods: Six persons with MS (Patient-Determined Disease Steps 3-5) participated in the study. Perceived fatigue and demographic information were taken at baseline. Muscle fatigability and mitochondria capacity was measured in the lower leg muscles before walking. Reported fatigue (VAFS, 0-10), gait variability, gait asymmetry, and static balance were measured before and immediately after a self-paced 6 minutes treadmill walk with slight elevation, and after 20 minutes of rest. Results: Participant’s baseline MFIS score ranged from 14 - 71. There was a 173% increase in reported fatigue scores after walking. Gait was impaired with a ~26% increase in gait variability and ~40% increase in gait asymmetry immediately after walking (Cohen’s D = 0.4, 0.3 respectively). There was also ~69% increase in balance postural sway with eyes opened and a ~20% increase with eyes closed (Cohen’s D = 0.5, 0.2 respectively). Gait and balance remained impaired after 20 minutes of rest. The decline in gait parameters after walking had a negative correlation with muscle endurance (r=-0.80, p=0.03), and mitochondrial capacity (r=-0.92, p

Our study used near-infrared spectroscopy (NIRS) to measure muscle oxidative capacity (mVmax) in the medial gastrocnemius, vastus lateralis, biceps brachii, and wrist flexor muscles in Cross-country (LEG-T) and Swimmer/Rowers (WHOLE-T) and controls. Young male adults: cross-country LEG-Tners (n=6) and swimmers/rowers (n=5), moderately fit (CONTROL, n=7) were tested. mVmax was measured as the rate of post-exercise recovery of oxygen consumption after a short bout of exercise using NIRS. Whole-body peak oxygen uptake (VO2peak) was determined during a continuous treadmill protocol. The lower limb muscles had 42% higher mVmax than upper limb muscles in all subjects, with significant differences in 10 of 12 pairwise comparisons (p< 0.05). The LEG-T group had higher mVmax values in both legs than CONTROL group (p< 0.05), while the WHOLE-T group had higher mVmax in the vastus lateralis (p = 0.048). There were no differences in the arm muscles of between the groups. The combined mVmax of both leg muscles in all groups correlated with VO2peak (r2=0.597). Muscle oxidative capacity was consistent with training status, and leg mitochondrial capacity correlated with maximal whole body oxidative capacity. These results support the use of NIRS measurements to characterize oxidative capacity in skeletal muscles of athletic populations.

Previous studies have used an accelerometer to evaluate muscle endurance. This study compared endurance index values using a video phone to an accelerometer. Eleven healthy subjects (19-22yrs) were electrically stimulated for 5 minutes at 5 Hz on the hamstring muscles. Four 10s videos were captured at 1080p and 60fps (~283,000 pixels) with the phone. Videos were analyzed using sequential correlations (consecutive 1-2, or consecutive skipping an image 1–3) of the video images between the electrodes. The magnitude of the decrease in the correlation was used to indicate movement. A triaxial accelerometer measured the resultant vector of the movements and the decrease in acceleration was used to indicate fatigue. Analysis using 1-3 produced higher delta R2 values compared to 1-2 (0.038+0.004; 0.020+0.001). Endurance index was 72.1+19.4% for the accelerometer and 71.1+18.6% for the phone images, p=0.64. The mean difference between the methods was not different from zero and the 90% confidence interval was within 5%. In conclusion, the consecutive correlations method detected decreases in movement due to fatigue. The video method provided equivalent values to the previously established accelerometer method to measure muscle endurance. These results support the use of video to assess muscle acceleration during muscle specific endurance test.

Near-Infrared Spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity (mVO2max) as the recovery rate constant of muscle metabolism after exercise. The current method requires as many as 50 short ischemic occlusions to generate 2 recovery rate constants. PURPOSE: To determine the effectiveness of using a 6-occlusion protocol (Mito6) versus one with 22 occlusions (Mito22) to measure muscle mitochondrial capacity. METHOD: In two independent data sets (bicep n=7, forearm A n=23), recovery curves were analyzed independently using both the Mito6 and Mito22 analyses. A third data set (Forearm B, n=16) was generated on forearm muscles of healthy subjects using four Mito6 tests performed in succession. Recovery rate constants were generated using a MATLAB routine. RESULTS: When calculated from the same data set, the recovery rate constants were not significantly different between the Mito22 and Mito6 analyses for the bicep (1.43+0.33min-1, 1.43+0.35min-1, p=0.81) and the forearm A (1.97+0.40min-1, 1.97+0.43min-1, p=0.90). The correlation between Mito22 and Mito6 recovery rate constants was y=1.07x-0.09, R2=0.90 for the bicep data and 1.00x+0.01, R2=0.85 for the forearm A data. When performing the four Mito6 tests in the Forearm B study; recovery rate constants were not different between tests (1.50±0.51 min-1, 1.42±0.54 min-1, 1.26±0.41 min-1, 1.29±0.47 min-1, P>0.05). CONCLUSIONS: Muscle mitochondrial capacity was not different between the Mito6 analysis and the longer Mito22 analysis. The Mito6 protocol was considered more practical as it used fewer ischemic occlusion periods, and multiple tests could be performed in succession in less time. There were no order effects for the rate constants of four repeated Mito6 tests of mitochondrial capacity, supporting the use of multiple tests to improve accuracy.

Endurance of the muscles of the neck are rarely studied. This study measured the endurance index (EI) of the sternocleidomastoid (SCM) and upper trapezius muscles of the neck (trap). The vastus lateralis (VL) was used for comparison. Skeletal muscle endurance of twelve healthy subjects, age 19&ndash, 22 years, were tested on their SCM and trap in random order on one day, VL was tested on a separate day. Participants were tested in the supine position for the SCM and VL muscles and the prone position for the trap. Muscle contractions consisted of a 5 Hz twitch electrical stimulation for 5 min. Muscle acceleration (resultant vector) was measured using a triaxial accelerometer. EI was the ending acceleration as a percentage of the maximal acceleration. The endurance index (EI) for the SCM, trap, and VL was 42.3 &plusmn, 13.0%, 42.3 &plusmn, 20.2%, and 92.9 &plusmn, 11.0%, respectively. The EI of the VL was significantly higher than the EI of the SCM (t(2,22) = 10.33, p &lt, 0.001) and the trap (t(2,22) = 7.625, p &lt, 0.001). The EI was not different between the SCM and the trap muscle (t(2,22) = 0.004, p = 0.997). In conclusion, the neck muscles had much less endurance than the muscles in the leg and could make fatigued athletes more susceptible to concussions caused by head impacts.

Background: Recent evidence suggests that skeletal muscle dysfunction is involved in disability progression in people with multiple sclerosis (MS). However, the relationship between muscle dysfunction and walking impairments in MS remains unclear. Thus, the cross-sectional relationships between muscle-specific oxidative capacity and walking endurance in women with MS were evaluated. Methods: Twenty women with MS (11 African American, 9 white) were tested. Muscle oxidative capacity of the medial gastrocnemius was measured using near-infrared spectroscopy after electrical stimulation. Muscle endurance was evaluated using accelerometer-based mechanomyography during electrical stimulation. Muscle strength was measured during maximal voluntary plantarflexion using handheld dynamometry. Walking function was measured using the Timed 25-Foot Walk test and the 6-Minute Walk Test (6MWT). Results: Reduced muscle oxidative capacity (R2 = 0.68–0.71, P < .01) and muscle endurance (R2 = 0.59–0.78, P < .01) were associated with lower Timed 25-Foot Walk time and 6MWT distance. Muscle strength was weakly correlated to 6MWT distance (R2 = 0.21, P = .02). No differences in muscle function or clinical outcome measures were found between African American and white subgroups. Women with moderate-to-severe disability (Expanded Disability Status Scale [EDSS] score, 5.0–6.5) had significantly reduced muscle oxidative capacity, muscle endurance, and walking ability compared with women with mild disability (EDSS score, 2.5–4.5). Conclusions: Reductions in muscle function in people with MS are related to declines in walking function across all levels of disability. Muscle dysfunction is not differentially related to walking impairment in African American and white women with MS.

Diaphragmatic function is important in treating respiratory failure. Muscle endurance has been measured using twitch electrical stimulation and accelerometer-based mechanomyography. The purpose of this study was to evaluate the reproducibility and the time to perform an endurance test on the diaphragm muscle using electrical stimulation of the phrenic nerve. Twenty healthy subjects (21.6±1.6yrs) were tested in the supine position on two separate occasions. Stimulation electrodes were placed on the left (n=18) or right (n=2) phrenic nerve underneath the sternocleidomastoid muscle. A tri-axial accelerometer was placed on the abdomen and 5 minutes of submaximal electrical stimulation at 5Hz was performed. The resultant vector of acceleration at peak and end acceleration was analyzed: endurance index = end/peak*100). The test was successfully completed 41/47 times. The endurance index for the two days was 73.8±9.4% and 72.6±11.1%, respectively. The time to find the phrenic nerve was 34.8±13.1s for the first 10 subjects and 13.0±2.8s for the second 10 subjects. For the second group, the mean difference in endurance between days was 0.03% with a 95% confidence interval of -1.6% to 1.5%. In conclusion, the diaphragm endurance test was reproducible with practice.

Muscle endurance has been measured using an electrical stimulation twitch protocol and an accelerometer. This protocol used stimulation frequencies of 2, 4, and 6 Hz over nine minutes. This study compared endurance index values using a shorter protocol of 5 Hz for 5 Minutes to the original nine minute protocol. Fifteen healthy subjects (19-22yrs) were electrically stimulated on the forearm muscles twice: one day for 5 minutes at 5 Hz and on another day for 3 minutes at each at 2, 4 and 6 Hz. A triaxial accelerometer measured the resultant vector of the movements and the decrease in acceleration was used to indicate fatigue. There was no difference in Endurance Index (EI) between the 5 and 9 minute protocols (63.2+18.7%, 64.1+19.8%, respectively, p=0.532). The correlation between the two EI measurements was y= 0.91x+4.99%, r2=0.93. Equivalency testing found the mean difference between EI values for the two methods was 0.88% with a 95% confidence interval of the difference in EI of -2.09 to 3.81%. In conclusion, the shorter 5 Hz five minute endurance index protocol provided similar results to the longer 2 ,4, 6 Hz nine minute protocol. These results support the use of the shorter protocol when measuring muscle specific endurance.

The impact of type 1 diabetes (T1D) on muscle endurance and oxidative capacity is currently unknown.PurposeMeasure muscle endurance and oxidative capacity of adults with T1D compared to controls.MethodsA cross-sectional study design with a control group was used. Subjects (19-37 years old) with T1D (n=17) and controls (n=17) were assessed with hemoglobin A1c (HbA1c) and casual glucose. Muscle endurance was measured with an accelerometer at stimulation frequencies of 2, 4, and 6 Hz for a total of nine minutes. Mitochondrial capacity was measured using near-infrared spectroscopy after exercise as the rate constant of the rate of recovery of oxygen consumption.ResultsT1D and control groups were similar in age, sex, height, and race. The T1D group had slightly higher BMI values and adipose tissue thickness over the forearm muscles. Casual glucose was 150±70 mg/dL for T1D and 98±16 mg/dL for controls (P=0.006). HbA1c of T1D subjects was 7.1±0.9% and 5.0±0.4% for controls (P−1 and control=1.8±0.4 min−1, P=0.29) or reperfusion rate (T1D= 8.8±2.8s and control=10.3±3.0s, P=0.88). There were no significant correlations between HbA1c and either muscle endurance, mitochondrial capacity or reperfusion rate.ConclusionsAdults with T1D did not have reduced oxidative capacity, muscle endurance or muscle reperfusion rates compared to controls. HbA1c also did not correlate with muscle endurance, mitochondrial capacity or reperfusion rates. Future studies should extend these measurements to older people or people with poorly-controlled T1D.

RationaleSupervised treadmill exercise for claudication in peripheral arterial disease is effective but poorly tolerated because of ischemic leg pain. Near infrared spectroscopy allows non-invasive detection of muscle ischemia during exercise, allowing for characterization of tissue perfusion and oxygen utilization during training.ObjectiveWe evaluated walking time, muscle blood flow, and muscle mitochondrial capacity in patients with peripheral artery disease after a traditional pain-based walking program and after a muscle oxygen-guided walking program.Method and resultsPatients with peripheral artery disease trained thrice weekly in 40-minute-long sessions for 12 weeks, randomized to oxygen-guided training ( n = 8, age 72 ± 9.7 years, 25% female) versus traditional pain-based training ( n = 10, age 71.6 ± 8.8 years, 20% female). Oxygen-guided training intensity was determined by maintaining a 15% reduction in skeletal muscle oxygenation by near infrared spectroscopy rather than relying on symptoms of pain to determine exercise effort. Pain free and maximal walking times were measured with a 12-minute Gardner treadmill test. Gastrocnemius mitochondrial capacity and blood flow were measured using near infrared spectroscopy. Baseline pain-free walking time was similar on a Gardner treadmill test (2.5 ± 0.9 vs. 3.6 ± 1.0 min, p = 0.5). After training, oxygen-guided cohorts improved similar to pain-guided cohorts (pain-free walking time 6.7 ± 0.9 vs. 6.9 ± 1.1 min, p ConclusionsOxygen-guided exercise training improves claudication comparable to pain-based training regimens. Adaptations in mitochondrial function rather than increases in limb perfusion may account for functional improvement. Increases in mitochondrial oxidative capacity may be proportional to the degree of tissue hypoxia during exercise.

Acute exercise-induced inflammation is implicated in mediating the beneficial adaptations to regular exercise. Evidence suggests that reduced oxygen and/or blood flow to contracting muscle alters cytokine appearance. However, the acute inflammatory responses to hypoxic/ischemic exercise have been documented with inconsistent results and may not accurately reflect the ischemia produced during exercise in patients with ischemic cardiovascular diseases. Therefore, we determined the extent to which local inflammation is involved in the response to ischemic exercise. Fourteen healthy males performed unilateral isometric forearm contractions for 30 min with and without experimental ischemia. Blood was drawn at baseline, 5 and 10 min into exercise, at the end of exercise, and 30, 60, and 120 min after exercise. Oxygen saturation levels, as measured by near-infrared spectroscopy, were reduced by 10% and 41% during nonischemic and ischemic exercise, respectively. Nonischemic exercise did not affect cytokine values. Ischemia enhanced concentrations of basic fibroblast growth factor, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and vascular endothelial growth factor during exercise, but IL-8 was not influenced by ischemic exercise. In conclusion, the present study demonstrates that ischemic, small-muscle endurance exercise elicits local inflammatory cytokine production compared with nonischemic exercise. NEW & NOTEWORTHY We demonstrate that ischemic, small-muscle endurance exercise elicits local inflammatory cytokine production compared with nonischemic exercise. The present study advances our knowledge of the inflammatory response to exercise in a partial ischemic state, which may be relevant for understanding the therapeutic effects of exercise training for people with ischemic cardiovascular disease-associated comorbidities.

Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yr, HbA1C = 6.3 ± 0.6%). Each participant completed the following four conditions: sedentary and postmeal exercise (5 × 10-min bouts of treadmill walking at 60% V̇o2max) with metformin and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-h time window and 2-h total area under the curve was assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-h peak ( P = 0.001) and 2-h area under the curve ( P = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined ( P < 0.05 vs. all other conditions: metformin/sedentary: 12 ± 3.4, metformin/exercise: 9.7 ± 2.3, washout/sedentary: 13.3 ± 3.2, washout/exercise: 11.1 ± 3.4 mmol/l). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared with either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy. NEW & NOTEWORTHY The interactive effects of metformin and exercise on key physiological outcomes remain an area of controversy. Findings from this study show that the combination of metformin monotherapy and moderate-intensity postmeal exercise led to beneficial reductions in postprandial glucose excursions. Postmeal exercise may be a useful strategy for the management of postprandial glucose in people on metformin.

Aims Type 2 diabetes treatment primarily focuses on reducing hyperglycemia, including postprandial glucose excursions. Hypoglycemic agents are used clinically to lower fasting and postprandial glucose. Metformin is the first-line therapy; however, if metformin is inadequate then ‘add-on’ hypoglycemic agents are implemented. Postmeal exercise has been shown to lower postprandial glucose. The aim of this study was to assess if postmeal exercise provides additional glucose-lowering benefit, beyond medication alone, in those on add-on hypoglycemic agents. Methods Postprandial glucose excursions in eight participants with type 2 diabetes (Age: 60 ± 10.7, HbA1C: 7.9 ± 2.3) being treated with add-on hypoglycemic agents were assessed during both drug-treated sedentary and drug-treated postmeal exercise conditions. Continuous glucose monitoring was used to assess peak and area under the glucose curve (AUC) during exercise, as well as peak within a 2-h time window, 2-h total and 2-h incremental AUC after a standardized breakfast meal. Postmeal exercise consisted of 3 × 10-min intervals of treadmill walking at 50% maximal oxygen uptake. Results Glucose peak (drug only: 13.8 ± 3.7, drug/exercise: 9.9 ± 2.7 mmol/L; p = 0.02) and AUC (drug only: 500 ± 136, drug/exercise: 357 ± 89 mmol/L × 40 min; p = 0.03) were reduced during postmeal exercise. Breakfast 2-h incremental AUC was also reduced (drug only: 585 ± 291, drug/exercise: 330 ± 294; p = 0.047). Discussion Post-breakfast exercise lowered glucose during the exercise bout, although this effect was not sustained on later meals.

Introduction: Spinal cord injury (SCI) results in skeletal muscle atrophy, increases in intramuscular fat, and reductions in skeletal muscle oxidative capacity. Endurance training elicited with neuromuscular electrical stimulation (NMES) may reverse these changes and lead to improvement in muscle metabolic health. Methods: Fourteen participants with complete SCI performed 16 weeks of home-based endurance NMES training of knee extensor muscles. Skeletal muscle oxidative capacity, muscle composition, and blood metabolic and lipid profiles were assessed pre- and post-training. Results: There was an increase in number of contractions performed throughout the duration of training. The average improvement in skeletal muscle oxidative capacity was 119%, ranging from –14% to 387% (P = 0.019). There were no changes in muscle composition or blood metabolic and lipid profiles. Conclusion: Endurance training improved skeletal muscle oxidative capacity, but endurance NMES of knee extensor muscles did not change blood metabolic and lipid profiles. Muscle Nerve 55: 669–675, 2017

Background: People with multiple sclerosis (MS) have identified “wellness” and associated behaviors as a high priority based on “social media listening” undertaken by the National MS Society (i.e. the Society). Objective: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. Method: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. Results: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society’s Wellness Research Working Group. Conclusion: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences.

Background Near-infrared spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity (mVO2max) as the recovery rate constant of muscle metabolism after exercise. The current method requires as many as 50 short ischemic occlusions to generate two recovery rate constants. Purpose To determine the validity and repeatability of using a 6-occlusion protocol versus one with 22 occlusions to measure muscle mitochondrial capacity. The order effect of performing multiple Mito6 test was also evaluated. Method In two independent data sets (bicep n = 7, forearm A n = 23), recovery curves were analyzed independently using both the 6 and 22 occlusion methods. A third data set (forearm B n = 16) was generated on the forearm muscles of healthy subjects using four 6-occlusion tests performed in succession. Recovery rate constants were generated using a MATLAB routine. Results When calculated from the same data set, the recovery rate constants were not significantly different between the 22 occlusion and 6 occlusion methods for the bicep (1.43 ± 0.33 min-1, 1.43 ± 0.35 min-1, p = 0.81) and the forearm A (1.97 ± 0.40 min-1, 1.97 ± 0.43 min-1, p = 0.90). Equivalence testing showed that the mean difference was not different than zero and the 90% confidence intervals were within 5% of the average rate constant. This was true for the Mito6 and the Mito5∗ approaches. Bland-Altman analysis showed a slope of 0.21 min-1 and an r of 0.045 for the bicep dataset and a slope of -0.01 min-1 and an r of 0.045 for the forearm A dataset. When performing the four 6-occlusion tests; recovery rate constants showed no order effects (1.50 ± 0.51 min-1, 1.42 ± 0.54 min-1, 1.26 ± 0.41 min-1, 1.29 ± 0.47 min-1, P > 0.05). Conclusion The Mito6 analysis is a valid and repeatable approach to measure mitochondrial capacity. The Mito6 protocol used fewer ischemic occlusion periods and multiple tests could be performed in succession in less time, increasing the practicality of the NIRS mitochondrial capacity test. There were no order effects for the rate constants of four repeated 6-occlusion tests of mitochondrial capacity, supporting the use of multiple tests to improve accuracy.

Background Supervised exercise training is recommended for intermittent claudication in peripheral artery disease (PAD), but the relationship between work achieved during exercise and clinical outcomes is not well described. As in other training modalities, increased effort measured by cumulative work production is expected to be translate into to positive performance adaptations. In settings of constrained limb blood flow, this relationship is unknown. In addition, the impact of exercise on skeletal muscle oxygen use capacity changes is unknown. Near infrared spectroscopy (NIRS) offers a method of characterizing skeletal muscle mitochondrial adaptations before and after training programs. Methods We enrolled subjects (n=17, age 71±8.8 years, 20% female) with PAD and intermittent claudication (ankle brachial index [ABI]=0.76±0.21) in a 12-week supervised training program, randomized to traditional pain-based training strategy versus hypoxia-based training (using NIRS to direct training). Muscle work was calculated based on training performance. NIRS-based determination of mitochondrial capacity and microvascular flow were measured at baseline and after 12 weeks. Results Subjects trained for an average of 32.9±5.9 sessions walking at 54.4±13.4 m/min per session. Subjects achieved a mean of average workload of 4767±5112 kilogram force meter (kpm) per session and an aggregate of 148536±148020 kpm for the training program. Baseline pain-free walking time of 2.95±2.10 minutes increased by a mean of 3.74±2.47 minutes. Increase in walking time was proportional to the average work level achieved per session, with a correlating trend to the overall work level performed over 12 weeks (r=0.543, p=0.024). There was no increase in blood flow measured by ABI or limb microcirculation perfusion index over the training period. Skeletal muscle mitochondrial capacity increased over the training period and correlated with the overall work performed (r=0.573, p=0.016). Figure 1 Conclusions Treadmill exercise rehabilitation for intermittent claudication may be guided by total dose of exercise and NIRS-based indices of mitochondrial capacity rather than pain-levels achieved or changes in perfusion measures. Acknowledgement/Funding American Heart Association

PURPOSE: This study examined the effects of repeated long-duration hyperoxic water immersions (WI)s at 1.35 atmospheres absolute (ATA) on neuromuscular endurance performance. We hypothesized that over a five-day period of consecutive, resting, long-duration hyperoxic WIs there would be a decrease to neuromuscular endurance performance and tissue oxygenation with the quadriceps muscle, but not with the forearm flexors. METHODS: Thirteen well-trained, male subjects completed five consecutive 6-hour resting WIs with 18-hour surface intervals during the dive week while breathing 100% oxygen at 1.35 atmospheres absolute (ATA). We assessed skeletal muscle endurance performance before and after each water immersion (WI), and 24 and 72 hours after the final WI. Muscular endurance assessments included 40% maximal handgrip endurance (MHE) and 50-repetition maximal isokinetic knee extensions. Near infrared spectroscopy (NIRS) was used to measure muscle oxidative capacity (MOC) of the vastus lateralis and localized muscle tissue oxygenation of the vastus lateralis and flexor carpi radialis. Simultaneously, we measured brachioradialis neuromuscular activation by surface electromyography (SEMG). RESULTS: MHE time-to-fatigue performance declined by 15% at WI 3 (p = 0.009) and by 17% on WI 5 (p = 0.002). Performance continued to decline by 22% at 24-hours post-WI (p < 0.001) and by 12% on 72-hours post-WI (p = 0.019). 50-repetition IK knee extension total work decreased by 5% (p = 0.002) on WI 3, and was further reduced by 7.5% and 12.3% (p=0.032) at pre-WI 5 and 24-hours post-WI, respectively. However, the rate of fatigue was 8% (p=0.033) and 30% (p = 0.017) lower at WI 3 and 24-hours post-WI when compared to WI 1, respectively, demonstrating the muscles were still fatigued from the previous hyperoxic WIs. We detected no significant limitations in oxygen off-loading kinetics during the exercise or MOC measurements. CONCLUSION: Repeated, resting, long-duration hyperoxic WIs caused significant reductions to muscular endurance but not to indirect measures of oxygen kinetics in load bearing and non-load bearing muscles.

Background: Near-infrared spectroscopy (NIRS) has been used to measure oxidative capacity, but regional differences have not been identified. Piano players are also a novel group of subjects for this lab. Methods: Controls (n = 13) and piano players (n = 8) were tested in a seated position on the right forearm. A fatigue test was performed for three minutes at 2, 4 and 6 Hz using electrical stimulation, which created an endurance index (EI) as the forearm fatigued. A six-cuff oxidative capacity test was performed using manual exercise to activate the muscle and allow for regional specificity. A rate constant (Rc) was generated from the mitochondrial capacity data. Results: Overall, piano players (Rc = 1.76 &plusmn, 0.6) and controls (Rc = 1.17 &plusmn, 0.3) have significant differences for the last two fingers (p = 0.01). While controls have significant differences between the index (Rc = 1.86 &plusmn, 0.5) and last two fingers (Rc = 1.17 &plusmn, 0.3) (p = 0.001), this difference was not observed in piano players. Overall, piano players (EI = 75.7 &plusmn, 12.3) and controls (EI = 73.0 &plusmn, 17.3) had no differences in endurance index values (p = 0.71). Conclusions: Piano players have significant differences in the mitochondrial capacity of the finger flexors that control the last two fingers compared to controls. The lack of difference between groups in the index fingers and overall endurance test suggests playing the piano produces training adaptations to the finger flexor muscles of the last two digits, which are rarely used by control subjects.

Near-Infrared Spectroscopy (NIRS) has been used to measure muscle mitochondrial capacity. The current method requires as many as 22 short ischemic occlusions to generate a recovery curve for mitochondrial capacity. PURPOSE: To determine the effectiveness of using a 6-occlusion analysis protocol to study muscle mitochondrial capacity. METHOD: Two independent, unidentified data sets were analyzed (bicep n=48, forearm n=41) from previous studies using a NIRS device (Artinis, Ltd.). Both data sets had two recovery tests that included 22 ischemic occlusions. A recovery rate used to indicate mitochondrial capacity was calculated two different ways (simultaneously). Each sample was analyzed with a MATLAB program; with a curve-fit for the 22 ischemic occlusions and curve matching for the first six ischemic cuffs and an end resting value. The two resulting rate constants were compared using correlations, both for the two data sets, good and bad fitting data, using the best 5 of 6 points for the 6 cuff approach. RESULTS: The rate constants were not significantly different between the 22 cmuff and 6 cuff for the total data sets: bicep (1.43+0.32min-1, 1.44+0.35min-1, p=0.56), forearm (1.94+0.42min-1, 1.95+0.44min-1, p=0.76). The average bicep rate constants, when compared to each other, had an equation of y=1.07x-0.09, R2=0.90. The average forearm rate constants, when compared to each other, had an equation of 0.98x+0.02, R2=0.93. CONCLUSIONS: The 6-Cuff analysis provided the same results as the longer 22-cuff. The 6-cuff approach is both shorter in time and uses less ischemic occlusion periods, increasing the practicality of the NIRS mitochondrial capacity test.