Skin and not dorsal root stimulation reduces hypertonus in thoracic motor complete spinal cord injury: a single case report.

On demand and localized treatment for excessive muscle tone after spinal cord injury (SCI) is currently not available. Here, we examine the reduction in leg hypertonus in a person with mid-thoracic, motor complete SCI using a commercial transcutaneous electrical stimulator (TES) applied at 50 or 150 Hz to the lower back and the possible mechanisms producing this bilateral reduction in leg tone. Hypertonus of knee extensors without and during TES, with both cathode (T11-L2) and anode (L3-L5) placed over the spinal column (midline, MID) or 10 cm to the left of midline (lateral, LAT) to only active underlying skin and muscle afferents, was simultaneously measured in both legs with the pendulum test. Spinal reflexes mediated by proprioceptive (H-reflex) and cutaneomuscular reflex (CMR) afferents were examined in the right leg opposite to the applied LAT TES. Hypertonus disappeared in both legs but only during thoracolumbar TES, and even during LAT TES. The marked reduction in tone was reflected in the greater distance both lower legs first dropped to after being released from a fully extended position, increasing by 172.8% and 94.2% during MID and LAT TES, respectively, compared with without TES. Both MID and LAT (left) TES increased H-reflexes but decreased the first burst, and lengthened the onset of subsequent bursts, in the cutaneomuscular reflex of the right leg. Thoracolumbar TES is a promising method to decrease leg hypertonus in chronic, motor complete SCI without activating spinal cord structures and may work by facilitating proprioceptive inputs that activate excitatory interneurons with bilateral projections that in turn recruit recurrent inhibitory neurons.NEW & NOTEWORTHY We present proof of concept that surface stimulation of the lower back can reduce severe leg hypertonus in a participant with motor complete, thoracic spinal cord injury (SCI) but only during the applied stimulation. We propose that activation of skin and muscle afferents from thoracolumbar transcutaneous electrical stimulation (TES) may recruit excitatory spinal interneurons with bilateral projections that in turn recruit recurrent inhibitory networks to provide on demand suppression of ongoing involuntary motoneuron activity.

No benefit of vitamin D supplementation on muscle function and health-related quality of life in primary cardiovascular prevention patients with statin-associated muscle symptoms: A randomized controlled trial.

BACKGROUND: Statins are the leading lipid-lowering drugs, reducing blood cholesterol by controlling its synthesis. Side effects are linked to the use of statins, in particular statin-associated muscle symptoms (SAMS). Some data suggest that vitamin D supplementation could reduce SAMS. OBJECTIVE: The purpose of this study was to evaluate the potential benefits of vitamin D supplementation in a randomized controlled trial. METHODS: Men (n = 23) and women (n = 15) (50.5 ± 7.7 years [mean ± SD]) in primary cardiovascular prevention, self-reporting or not SAMS, were recruited. Following 2 months of statin withdrawal, patients were randomized to supplementation (vitamin D or placebo). After 1 month of supplementation, statins were reintroduced. Before and 2 months after drug reintroduction, muscle damage (creatine kinase and myoglobin) was measured. Force (F), endurance (E) and power (P) of the leg extensors (ext) and flexors (fle) and handgrip strength (FHG) were also measured with isokinetic and handheld dynamometers, respectively. The Short Form 36 Health Survey (SF-36) questionnaire and a visual analog scale (VAS) were administrated to assess participants' self-reported health-related quality of life and SAMS intensity, respectively. Repeated-measures analysis was used to investigate the effects of time, supplementation, and their interaction, according to the presence of SAMS. RESULTS: Despite no change for objective measures, subjective measures worsened after reintroduction of statins, independent of supplementation (VAS, SF-36 mental component score, all p < 0.05). However, no interaction between time and supplementation according to the presence of SAMS was observed for any variables. CONCLUSIONS: Vitamin D supplementation does not appear to mitigate SAMS.

Prevention of muscle atrophy in ICU patients without nerve injury by neuromuscular electrical stimulation: a randomized controlled study.

BACKGROUND: Extensive muscle atrophy is a common occurrence in orthopaedics patients who are bedridden or immobilized. The incidence is higher in intensive care unit (ICU) inpatients. There is still controversy about how to use neuromuscular electrical stimulation (NMES) in ICU patients. We aim to compare the effectiveness and safety of NMES to prevent muscle atrophy in intensive care unit (ICU) patients without nerve injury. METHODS: ICU patients without central and peripheral nerve injury were randomized into experimental group I (Exp I: active and passive activity training (APAT) + NMES treatment on the gastrocnemius and tibialis anterior muscle), experimental group II (Exp II: APAT + NMES treatment on gastrocnemius alone), and control group (Ctl: APAT alone). Changes in the strength of gastrocnemius, the ankle range of motion, and the muscle cross-section area of the lower leg were evaluated before and after the intervention. Also, changes in prothrombin time, lactic acid, and C-reactive protein were monitored during the treatment. RESULTS: The gastrocnemius muscle strength, ankle joint range of motion, and cross-sectional muscle area of the lower leg in the three groups showed a downward trend, indicating that the overall trend of muscle atrophy in ICU patients was irreversible. The decrease in gastrocnemius muscle strength in Exp I and Exp II was smaller than that in the control group (P < 0.05), but there was no difference between Exp I and Exp II. The decrease in active ankle range of motion and cross-sectional area of the lower leg Exp I and Exp II was smaller than that in the control group (P < 0.05), and the decrease in Exp I was smaller than that of Exp II (all P < 0.05). The curative effect in Exp I was better than in Exp II. There were no significant differences in the dynamic changes of prothrombin time, lactic acid, and C-reactive protein during the three groups (P > 0.05). CONCLUSION: In addition to early exercise training, NMES should be applied to prevent muscle atrophy for patients without nerve injury in ICU. Also, simultaneous NMES treatment on agonist/antagonist muscle can enhance the effect of preventing muscle atrophy. TRIAL REGISTRATION: This study was prospectively registered in China Clinical Trial Registry ( www.chictr.org.cn ) on 16/05/2020 as ChiCTR2000032950.

Effect of hybrid FES exercise on body composition during the sub-acute phase of spinal cord injury.

OBJECTIVES: To determine the Effect of Hybrid functional electrically stimulated (FES) Exercise on Body Composition during the Sub-acute Phase of Spinal Cord Injury (SCI). DESIGN: Randomized Clinical Trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Patients within sub-acute phase (3-24 months) of SCI. INTERVENTIONS: We investigated if high-intensity exercise training via the addition of functional electrically stimulated (FES) leg muscles, provides sufficient stimulus to mitigate against body composition changes in the sub-acute phase after SCI. MAIN OUTCOME MEASURES: We explored potential effects of FES row training (FESRT) on body fat gain, lean mass loss, and cardiometabolic parameters and compared the effects of 6-month of FESRT (n = 18) to standard of care (SOC, n = 13). Those in SOC were crossed over to FESRT. RESULTS: FESRT resulted in greater exercise capacity and a tendency for lesser total body fat accumulation with a significant increase in total and leg lean mass (p<0.05). In addition pelvis and total bone mineral density declines were significantly less (p<0.05). Compared to SOC, FESRT did not lead to any significant difference in insulin sensitivity or serum lipids. However, HbA1C levels were significantly decreased in SOC participants who crossed over to 6-month FESRT. CONCLUSION: FESRT early after SCI provides a sufficient stimulus to mitigate against detrimental body composition changes. This may lead to prevention of losses in lean mass, including bone.

Effectiveness of a Novel Contralaterally Controlled Neuromuscular Electrical Stimulation for Restoring Lower Limb Motor Performance and Activities of Daily Living in Stroke Survivors: A Randomized Controlled Trial.

Background: Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce. Objective: To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients. Methods: Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group (n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 µs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl-Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle. Results: Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment (p < 0.01). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group (p < 0.05). Conclusion: CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning.

Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms responsible for these negative traits. With the complexities surrounding these unknowns and the lack of progress to date in development of effective interventions, there is a need for alternative approaches. Metabolomics is the study of the full array of metabolites within cells or tissues, which collectively constitute the metabolome. As metabolomics allows for the assessment of the cellular metabolic state in response to physiological stimuli, any chronic change in the metabolome is likely to reflect adaptation in the physiological phenotype of an organism. This, therefore, provides a holistic and unbiased approach that could be applied to potentially uncover important novel facets in the pathophysiology of muscle decline in ageing and disease, as well as identifying prognostic markers of those at risk of decline. This review will aim to highlight the current knowledge and potential impact of metabolomics in the study of muscle mass loss and deconditioning in humans and will highlight key areas for future research.

Restorative potential of (-)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue.

We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

The use of BCAA to decrease delayed-onset muscle soreness after a single bout of exercise: a systematic review and meta-analysis.

Branched-chain amino acids (BCAA) are used as a recovery method after exercise-induced muscle damage (EIMD). Although data suggest that BCAA may alleviate the delayed-onset muscle soreness (DOMS) evoked by EIMD, there is no consensus about the most effective supplementation protocol. To investigate the effects of BCAA on DOMS after a single exercise session that caused EIMD, a systematic review and meta-analysis were conducted on the effectiveness of BCAA supplementation to reduce DOMS symptoms in healthy subjects after a single session of EIMD. Randomized clinical trials (RCT) were searched in Medline, Cochrane Library, Science Direct, SciELO, LILACS, SciVerse Scopus, Springer Link journals, Wiley Online Library, and Scholar Google, until May 2021. Ten RCTs were included in the systematic review and nine in the meta-analysis. Seven studies demonstrated that BCAA reduced DOMS after 24 to 72 h. BCAA doses of up to 255 mg/kg/day, or in trained subjects, for mild to moderate EIMD, could blunt DOMS symptoms. However, high variability between studies due to training status, different doses, time of treatment, and severity of EIMD do not allow us to conclude whether BCAA supplementation is efficient in untrained subjects, applied acutely or during a period of pre to post days of EIMD, and at higher doses (> 255 mg/kg/day). The overall effects of BCAA on DOMS after a single session of exercise were considered useful for improving muscle recovery by reducing DOMS in trained subjects, at low doses, in mild to moderate EIMD, and should not be administered only after the EIMD protocol.

Impact of ß-hydroxy-ß-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT.

PURPOSE: Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process. METHODS: Prospective randomized, placebo-controlled double blind trial. INCLUSION CRITERIA: ICU patients depending on mechanical ventilation on day 3 having a functional gastrointestinal tract. They were randomized to HMB (3 g/day) or placebo (maltodextrin) from day 4 on for 30 days. PRIMARY OUTCOME: magnitude of loss of skeletal muscle area (SMA) of the quadriceps femoris measured by ultrasound at days 4 and 15. SECONDARY OUTCOMES: body composition, change in protein metabolism assessed by amino acids tracer pulse, and global health at 60 days. Data are mean [95% CI]. Statistics by ANCOVA with correction for confounders sex, age and/or BMI. RESULTS: Thirty patients completed the trial, aged 65 [59, 71] years, SAPS2 score 48 [43, 52] and SOFA 8.5 [7.4, 9.7]. The loss of total SMA was 11% between days 4 and 15 (p < 0.001), but not different between the groups (p = 0.86). In the HMB group, net protein breakdown (Δ Estimate HMB-Placebo: -153 [-242, -63]; p = 0.0021) and production of several amino acid was significantly reduced, while phase angle increased more (0.66 [0.09, 1.24]; p = 0.0247), and SF-12 global health improved more (Δ Estimate HMB-Placebo: 27.39 [1.594, 53.19], p = 0.04). CONCLUSION: HMB treatment did not significantly reduce muscle wasting over 10 days of observation (primary endpoint), but resulted in significantly improved amino acid metabolism, reduced net protein breakdown, a higher phase angle and better global health. CLINICALTRIALS. GOV IDENTIFIER: NCT03628365.

The Effects of Crocodile Blood Supplementation on Delayed-Onset Muscle Soreness.

Delayed-onset muscle soreness (DOMS) is associated with increases in acute inflammatory and biochemical markers, muscle swelling, pain, and reduced functional performance. This study aimed to investigate the preventative effects of crocodile blood supplementation on DOMS induced by eccentric exercise. Sixteen healthy males were randomly allocated to either a crocodile blood (CB, n = 8) or a placebo (PL, n = 8) treatment. Participants receiving the CB treatment consumed four capsules of freeze-dried CB powder (1 g day-1) over 18 days. Participants receiving the other treatment were administered a placebo over the same period. An eccentric exercise protocol was performed, and functional performance, visual analogue scale (VAS)-measured pain, knee range of movement (ROM), thigh circumference (swelling), and cytokines, enzymes, and biochemical parameters were assessed immediately after exercise as well as after 24 h, 48 h, and 72 h. CB supplementation could significantly maintain maximum voluntary isometric contraction (MVIC) at 24 h (p = 0.001) and 48 h after exercise (p = 0.001) when comparing values at different times for the CB group. In the CB group, thigh circumference decreased only immediately after eccentric exercise (p = 0.031) in comparison with pre-eccentric exercise values. An 18-day supplementation (1 g day-1) of crocodile blood does aid in the maintenance of functional performance and muscle swelling after eccentric exercise. Our data indicate that 1 g day-1 of crocodile blood supplementation should be safe for human consumption.

Peripheral Blood T Cell Gene Expression Responses to Exercise and HMB in Sarcopenia.

BACKGROUND: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. METHODS: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. RESULTS: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. CONCLUSIONS: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.

Consumption of New Zealand Blackcurrant Extract Improves Recovery from Exercise-Induced Muscle Damage in Non-Resistance Trained Men and Women: A Double-Blind Randomised Trial.

BACKGROUND: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. METHODS: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day-1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. RESULTS: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. CONCLUSIONS: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD.

Maintenance of Skeletal Muscle to Counteract Sarcopenia in Patients with Advanced Chronic Kidney Disease and Especially Those Undergoing Hemodialysis.

Life extension in modern society has introduced new concepts regarding such disorders as frailty and sarcopenia, which has been recognized in various studies. At the same time, cutting-edge technology methods, e.g., renal replacement therapy for conditions such as hemodialysis (HD), have made it possible to protect patients from advanced lethal chronic kidney disease (CKD). Loss of muscle and fat mass, termed protein energy wasting (PEW), has been recognized as prognostic factor and, along with the increasing rate of HD introduction in elderly individuals in Japan, appropriate countermeasures are necessary. Although their origins differ, frailty, sarcopenia, and PEW share common components, among which skeletal muscle plays a central role in their etiologies. The nearest concept may be sarcopenia, for which diagnosis techniques have recently been reported. The focus of this review is on maintenance of skeletal muscle against aging and CKD/HD, based on muscle physiology and pathology. Clinically relevant and topical factors related to muscle wasting including sarcopenia, such as vitamin D, myostatin, insulin (related to diabetes), insulin-like growth factor I, mitochondria, and physical inactivity, are discussed. Findings presented thus far indicate that in addition to modulation of the aforementioned factors, exercise combined with nutritional supplementation may be a useful approach to overcome muscle wasting and sarcopenia in elderly patients undergoing HD treatments.

Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling Via Increasing SAM Level.

SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.

L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial.

Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.

Evaluation of the Efficacy of Supplementation with Planox® Lemon Verbena Extract in Improving Oxidative Stress and Muscle Damage: A Randomized Double-Blind Controlled Trial.

Excessive exercise load can cause muscle soreness and fatigue, as well as inflammation and oxidative stress. Lemon verbena (Aloysia triphylla; Lippia citriodora) is often used as a spice in tea or beverages. Its leaves are rich in polyphenols, which have antioxidant and anti-inflammatory bioactivities. In the present study, we investigated whether supplementation with Planox® lemon verbena extract (LVE) could improve muscle damage and biochemical indicators after exhaustive exercise challenge. All subjects (30 males and 30 females) underwent a double-blind trial and were randomly divided into a placebo group (0 mg/human/day) and an LVE supplement group (400 mg/human/day), with gender-equal distribution. All subjects started supplementation 10 days before exhaustive exercise and continued it until all tests were completed. Before the intervention, after the exhaustive exercise, and on the following 3 days, the participants underwent 12-minute Cooper running/walking; blood collection; assessments of pain, muscle stiffness, maximum jump heights, and isometric maximum muscle strength. The results showed that supplementation with LVE effectively increased GPx and reduced CK, IL-6, 8-OHdG and muscle pain after the exhaustive exercise, but it had significant effect on strength recovery. In summary, LVE is a safe and edible natural plant extract that can reduce muscle damage and soreness after exercise. This trial was registered at clinicaltrials.gov as NCT04742244.

Diet and Exercise Interventions in Patients With Pancreatic Cancer: A Scoping Review.

ABSTRACT: Diet and exercise interventions may help reverse malnutrition and muscle wasting common in pancreatic cancer. We performed a scoping review to identify the knowledge gaps surrounding diet and exercise interventions. We searched PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature, Embase, ProQuest Theses and Dissertations, and Google Scholar using the umbrella terms of "pancreatic cancer," "diet/nutrition," and "exercise." Included were articles reporting on ambulatory adults with diagnosed pancreatic cancer. Excluded were studies examining prevention and/or risk, animal, or cell lines. Of the 15,708 articles identified, only 62 met the final inclusion criteria. Almost half of the articles were randomized controlled studies (n = 27). Most studies were from the United States (n = 20). The majority examined dietary interventions (n = 41), with 20 assessing the use of omega-3 fatty acids. Exercise interventions were reported in 13 studies, with 8 examining a diet and exercise intervention. Most studies were small and varied greatly in terms of study design, intervention, and outcomes. We identified 7 research gaps that should be addressed in future studies. This scoping review highlights the limited research examining the effect of diet and exercise interventions in ambulatory patients with pancreatic cancer.

Conveyance of cortical pacing for parkinsonian tremor-like hyperkinetic behavior by subthalamic dysrhythmia.

Parkinson's disease is characterized by both hypokinetic and hyperkinetic symptoms. While increased subthalamic burst discharges have a direct causal relationship with the hypokinetic manifestations (e.g., rigidity and bradykinesia), the origin of the hyperkinetic symptoms (e.g., resting tremor and propulsive gait) has remained obscure. Neuronal burst discharges are presumed to be autonomous or less responsive to synaptic input, thereby interrupting the information flow. We, however, demonstrate that subthalamic burst discharges are dependent on cortical glutamatergic synaptic input, which is enhanced by A-type K+ channel inhibition. Excessive top-down-triggered subthalamic burst discharges then drive highly correlative activities bottom-up in the motor cortices and skeletal muscles. This leads to hyperkinetic behaviors such as tremors, which are effectively ameliorated by inhibition of cortico-subthalamic AMPAergic synaptic transmission. We conclude that subthalamic burst discharges play an imperative role in cortico-subcortical information relay, and they critically contribute to the pathogenesis of both hypokinetic and hyperkinetic parkinsonian symptoms.

The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal cord-injured athletes.

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to ß-alanine supplementation in spinal cord-injured athletes, 16 male athletes with paraplegia were randomized (2:1 ratio) to receive ß-alanine (n = 11) or placebo (PL, n = 5). They consumed 6.4 g/day of ß-alanine or PL for 28 days. Muscle biopsies of the active deltoid and the inactive vastus lateralis (VL) were taken before and after supplementation. MCarn in the VL was also compared with the VL of a group of individuals without paraplegia (n = 15). MCarn was quantified in whole muscle and in pools of individual fibers by high-performance liquid chromatography. MCarn was higher in chronically inactive VL vs. well-trained deltoid (32.0 ± 12.0 vs. 20.5 ± 6.1 mmol/kg DM; P = 0.018). MCarn was higher in inactive vs. active VL (32.0 ± 12.0 vs. 21.2 ± 7.5 mmol/kg DM; P = 0.011). In type-I fibers, MCarn was significantly higher in the inactive VL than in the active deltoid (38.3 ± 4.7 vs. 27.3 ± 11.8 mmol/kg DM, P = 0.014). MCarn increased similarly between inactive VL and active deltoid in the ß-alanine group (VL: 68.9 ± 55.1%, P = 0.0002; deltoid: 90.5 ± 51.4%, P < 0.0001), with no changes in the PL group. MCarn content was higher in the inactive VL than in the active deltoid and the active VL, but this is probably a consequence of fiber type shift (type I to type II) that occurs with chronic inactivity. Chronically inactive muscle showed an increase in MCarn after BA supplementation equally to the active muscle, suggesting that carnosine accretion following ß-alanine supplementation is not influenced by muscle inactivity.

Altered Vestibular Balance Function in Combat Sport Athletes.

Combat sports pose a risk for accumulative injuries to the nervous system, yet fighters have remained an understudied population. Here, our purpose was to determine whether repetitive blows to the head have an effect on vestibular balance reflexes in combat sports athletes. We compared lower-limb muscle responses evoked with electrical vestibular stimuluation (EVS) between fighters (boxing/muay thai) and non-fighter controls. Each participant received stochastic vestibular stimulation (0-25 Hz, ±3 mA) over their mastoid processes while they stood relaxed with their head to the left or right. Surface electromyography was recorded from the medial gastrocnemius and soleus muscles bilaterally. Short and medium latency response (SLR/MLR) peaks were significantly delayed in the fighter group compared to controls. SLR and MLR peak amplitudes were also significantly lower in fighters. Fighter-estimated cumulative repetitive head impact (RHI) events demonstrated strong positive correlations with the timing of SLR and MLR peaks. Cumulative RHI events also negatively correlated with peak MLR amplitude and response gain at frequencies above 5 Hz. Our results provide evidence of a progressive vestibular impairment in combat sports athletes, potentially resulting from blows to the head accumulated in sparring practice and competitive bouts throughout their careers. Taken together, EVS-based vestibular assessments may provide a valuable clinical diagnostic tool and help better inform "return-to-play" and career-length decisions for not only combat sports athletes, but potentially other populations at risk of RHIs.