Body composition and aging: cross-sectional results from the INSPIRE study in people 20 to 93 years old.

Aging is characterized by several major changes, including altered body composition, which is associated with numerous negative clinical consequences such as sarcopenia, osteoporosis, and frailty. The study is to evaluate body composition parameters depending on age and sex in a population ranging from the young adult to the very old, and to identify break points in the association between body composition and age. In this cross-sectional study, we included the enrolment population of the French INSPIRE-T prospective cohort, accounting for 915 subjects (62% female). Age ranged from 20 to 93 years, median age (years) was 63 (IQR 27). Body composition (lean mass, fat mass, and bone mineral content) was assessed with dual-X-ray absorptiometry (DXA). Different break points in the relationship between age and body composition variables in males and females were identified using a segmented regression analysis adjusted on physical activity, nutritional status, educational level, and comorbidities. Lean mass decreased from the age of 55 years for males (CI 95% 44-66) and 31 years for females (CI 95% 23-39). For fat mass, we observed a trend towards an increase with age for males. For females, we observed an increase with age up to age 75 (CI 95% 62-86), followed by a decreasing trend. In this study, we described the relationship between body composition and age as a function of sex, establishing a foundation for further studies on predictive biomarkers of age-related body composition alteration.

Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood.

BACKGROUND: The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course. METHODS: Data from 499 community-dwelling adults (63% female) aged 20-92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O2max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum. RESULTS: Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age2 × SB × MVPA: B = -7E-08, SE = 3E-08, P < 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age2 × MVPA: B = 3E-06, SE = 1E-06, P < 0.05), chair-rise performance (age × MVPA: B = -9E-05, SE = 4E-05, P < 0.05) and V̇O2max (MVPA at 21 years: B = 3E-02, SE = 7E-03, P < 0.05; age × MVPA: B = -5E-04, SE = 2E-04, P < 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: B = -1E-04, SE = 6E-05, P < 0.05) and chair-rise performance (age × SB: B = 1E-05, SE = 7E-06, P < 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific. CONCLUSIONS: This cross-sectional study demonstrated that reduced sedentary time and increased activity duration were independently and synergistically associated with an attenuated age-related loss in physical capacity. These findings need to be confirmed with longitudinal data but encourage both adopting an active lifestyle and reducing sedentary time as preventive measures against physical aging.

The Impact of COVID-19 on the Response to Hypoxia.

Louis, Alexandre, Charlotte Pröpper, Yann Savina, Corentin Tanne, Guy Duperrex, Paul Robach, Pascal Zellner, Stéphane Doutreleau, Jean-Michel Boulet, Alain Frey, Fabien Pillard, Cristina Pistea, Mathias Poussel, Thomas Thuet, Jean-Paul Richalet, and François Lecoq-Jammes. The impact of COVID-19 on the response to hypoxia. High Alt Med Biol. 24:321-328, 2023. Background: Severe high-altitude illness (SHAI) and coronavirus disease 2019 (COVID-19), while differing in most aspects of pathophysiology, both involve respiratory capacity. We examined the long-term impact of COVID-19 on response to hypoxia in individuals free of symptoms but having tested positive during the pandemic. The need for recommendations for such individuals planning a stay at high altitude are discussed. Methods: This multicenter study recruited participants from the multiSHAI cohort, all of whom had previously undergone a hypoxic exercise test. These participants were classified into two groups depending on whether they had since suffered mild-to-moderate COVID-19 (COVID+) or not (Control) and then asked to retake the test. Primary outcomes were: desaturation induced by hypoxia at exercise (ΔSpE), hypoxic cardiac response at exercise, hypoxic ventilatory response at exercise, and SHAI risk score. Results: A total of 68 participants retook the test, 36 classified in the COVID+ group. Analyses of primary outcomes showed no significant differences between groups. However, the COVID+ group showed significantly increased ventilation (VE) parameters during both hypoxic (p = 0.003) and normoxic exercise (p = 0.007). However, only the VE/oxygen consumption relationship during hypoxic exercise was significantly different. Conclusion: This study demonstrates no negative impact of COVID-19 on response to hypoxia as evaluated by the Richalet test. Clinical Trial Registration: NTC number: NCT05167357.

ANT1 overexpression models: Some similarities with facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. Adenine nucleotide translocator 1 (ANT1), the only 4q35 gene involved in mitochondrial function, is strongly expressed in FSHD skeletal muscle biopsies. However, its role in FSHD is unclear. In this study, we evaluated ANT1 overexpression effects in primary myoblasts from healthy controls and during Xenopus laevis organogenesis. We also compared ANT1 overexpression effects with the phenotype of FSHD muscle cells and biopsies. Here, we report that the ANT1 overexpression-induced phenotype presents some similarities with FSHD muscle cells and biopsies. ANT1-overexpressing muscle cells showed disorganized morphology, altered cytoskeletal arrangement, enhanced mitochondrial respiration/glycolysis, ROS production, oxidative stress, mitochondrial fragmentation and ultrastructure alteration, as observed in FSHD muscle cells. ANT1 overexpression in Xenopus laevis embryos affected skeletal muscle development, impaired skeletal muscle, altered mitochondrial ultrastructure and led to oxidative stress as observed in FSHD muscle biopsies. Moreover, ANT1 overexpression in X. laevis embryos affected heart structure and mitochondrial ultrastructure leading to cardiac arrhythmia, as described in some patients with FSHD. Overall our data suggest that ANT1 could contribute to mitochondria dysfunction and oxidative stress in FSHD muscle cells by modifying their bioenergetic profile associated with ROS production. Such interplay between energy metabolism and ROS production in FSHD will be of significant interest for future prospects.

Evaluation of the impact of the COVID-19 lockdown on the quality of life of patients monitored for cancer who practice an adapted physical activity: rugby for health.

PURPOSE: The benefits of regular physical exercise on the tolerability of cancer treatments, quality of life and survival rates post-diagnosis have been demonstrated but all supervised physical activities have been interrupted due to the global health crisis and the need for lockdown to halt the spread of SARS-CoV-2. To reintroduce activities post-lockdown, we wanted to assess the impact of the COVID-19 lockdown on the quality of life and the psychological status of patients who practice an adapted physical activity such as rugby for health. METHODS: The evaluation was conducted in two phases: an initial self-questionnaire comprised of 42 questions sent to all participants to assess the impact of lockdown and a second assessment phase in the presence of the participants. We assessed anthropometric data, functional fitness parameters, quality of life and the psychosocial status of the subjects. The data were compared to pre-lockdown data as part of a standardised follow-up procedure for patients enrolled in the programme. RESULTS: 105/120 (87.5%) individuals responded to the rapid post-lockdown survey analysis. In 20% of the cases, the patients reported anxiety, pain, a decline in fitness and a significant impact on the tolerability of cancer treatments. Twenty-seven patients agreed to participate in the individual analysis. Following lockdown, there was a significant decrease in the intensity of physical activity (p = 8.223e-05). No post-lockdown changes were noted in the assessments that focus on the quality of life and the level of psychological distress. Conversely, there was a significant correlation between the total of high energy expended during lockdown and the quality of life (p = 0.03; rho = 0.2248) and the level of psychological distress post-lockdown (p = 0.05; rho = - 0.3772). CONCLUSION: Lockdown and reduced physical activity, particularly leisure activities, did not impact the overall health of the patients. However, there was a significant correlation with the level of physical activity since the higher the level of physical activity, the better the quality of life and the lower the level of psychological distress.

Validation of a Score for the Detection of Subjects with High Risk for Severe High-Altitude Illness.

PURPOSE: A decision tree based on a clinicophysiological score (severe high-altitude illness (SHAI) score) has been developed to detect subjects susceptible to SHAI. We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ), and to specify the rule for a progressive acclimatization. METHODS: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of the SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of the SHAI score, ACZ prescription, and use and fulfillment of the acclimatization rule. RESULTS: The occurrence of SHAI was 22.6%, similar to what was observed 18 yr before (23.7%), whereas life-threatening forms of SHAI (high-altitude pulmonary and cerebral edema) were less frequent (2.6%-0.8%, P = 0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400-m daily altitude gain were respected (P < 0.001). CONCLUSIONS: This multicenter study confirmed the interest of the SHAI score in predicting the individual risk for SHAI. The conditions for an optimized acclimatization (400-m rule) were also specified, and we proposed a rational decision tree for the prescription of ACZ, adapted to each individual tolerance to hypoxia.

What Is the Impact of Physical Effort on the Diagnosis of Concussion?

OBJECTIVE: Sport-related concussion commonly occurs in contact sports such as rugby. To date, diagnosis is based on the realization of clinical tests conducted pitch-side. Yet, the potential effect of prior physical effort on the results of these tests remains poorly understood. The purpose of this study was to determine whether preceding physical effort can influence the outcome of concussion assessments. DESIGN: Prospective observational study. SETTING: University Medicine Center. PATIENTS: A cohort of 40 subjects (20 rugby players and 20 athletes from a range of sports). INTERVENTION: A concussion assessment was performed immediately after physical activity. After a period of 6 months and under the same experimental conditions, the same cohort performed the same tests in resting conditions. MAIN OUTCOME MEASURES: Results of concussion tests. RESULTS: In both cohorts, the comparison for postexercise and rest assessments demonstrated a most likely moderate-to-very large increase in the number of symptoms, severity of symptoms, and balance error scoring system score. In the rugby cohort, scores for concentration, delayed memory and standardized assessment of concussion (SAC), likely-to-most likely decreased following completion of physical activity compared with baseline values. The between-cohort comparison reported a most likely greater impact after exercise in the rugby players for delayed recall (0.73 ± 0.61) and SAC score (0.75 ± 0.41). CONCLUSIONS: Physical activity altered the results of concussion diagnostic tests in athletes from a range of sports and notably in rugby players. Therefore, physical efforts before the concussion incident should be accounted for during pitch-side assessments and particularly during rugby competition and training.

The exerkine apelin reverses age-associated sarcopenia.

Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons. Mice deficient in either apelin or its receptor (APLNR) presented dramatic alterations in muscle function with increasing age. Various strategies that restored apelin signaling during aging further demonstrated that this peptide considerably enhanced muscle function by triggering mitochondriogenesis, autophagy and anti-inflammatory pathways in myofibers as well as enhancing the regenerative capacity by targeting muscle stem cells. Taken together, these findings revealed positive regulatory feedback between physical activity, apelin and muscle function and identified apelin both as a tool for diagnosis of early sarcopenia and as the target of an innovative pharmacological strategy to prevent age-associated muscle weakness and restore physical autonomy.

Isoprostanes as markers for muscle aging in older athletes.

INTRODUCTION: Production of isoprostanes (IsoPs) is enhanced after acute, intense, and prolonged exercise, in untrained subjects. This effect is greater in older subjects. The present study aims to delineate the profile of acute-exercise-induced IsoPs levels in young and older endurance-trained subjects. METHODS: All included subjects were male, young (n = 6; 29 yrs ± 5.7) or older (n = 6; 63.7 yrs ± 2.3), and competitors. The kinetics of F2-IsoPs in blood-sera was assessed at rest, for the maximal aerobic exercise power (MAP) corresponding to the cardio-respiratory fitness index and after a 30-min recovery period. RESULTS: No significant time effect on F2-IsoPs kinetics was identified in young subjects. However, in older athletes, F2-IsoPs blood-concentrations at the MAP were higher than at rest, whereas these blood-concentrations did not differ between rest and after the 30-min recovery period. CONCLUSION: Because plasma glutathione (GSH) promotes the formation of some F2-IsoPs, we suggest that the surprising decrease in F2-IsoPs levels in older subjects would be caused by decreased GSH under major ROS production in older subjects. We argue that the assessment F2-IsoPs in plasma as biomarkers of the aging process should be challenged by exercise to improve the assessment of the functional response against reactive oxygen species in older subjects.

Determination of Cardiac Output in Pulmonary Hypertension Using Impedance Cardiography.

BACKGROUND: Cardiac output (CO) is a prognostic factor in pulmonary hypertension (PH). Right heart catheterisation using the direct Fick method or thermodilution (TD) is the reference technique for CO measurement. Impedance cardiography (IPc) is a known non-invasive method of measuring CO. OBJECTIVES: In our study, we assume that the measurement of CO by IPc using the PHYSIOFLOW® system is as accurate as TD or using the direct Fick method in patients with PH in group 1 or group 4. METHODS: A total of 75 patients were enrolled in a prospective study carried out at the hypertension reference centre of Toulouse University Hospital. Right heart catheterisation was performed for the diagnosis or follow-up of the disease. CO was measured using the Fick method, TD, and IPc simultaneously. A Bland-Altman analysis was plotted. RESULTS: CO was 5.7 ± 1.9 L/min as measured by the Fick method, 5.4 ± 1.5 L/min by TD, and 5.5 ± 1.7 L/min by IPc. The bias between CO measurements by IPc and the direct Fick method was 0.149 L/min (95% CI, -0.298 to 0.596). The bias between CO measurements by IPc and the TD method was -0.153 L/min (95% CI, -0.450 to 0.153). The correlation decreased with the more extreme CO values (< 3 L/min or > 7 L/min). A few factors changed the agreement between measurements (BMI or membership in group 4). CONCLUSION: To conclude, this study shows that the measurement of CO by IPc in PH patients is reliable compared to the direct Fick method and TD obtained by right heart catheterisation. This accuracy decreases for extreme CO values.

Whole-body strength training with Huber Motion Lab and traditional strength training in cardiac rehabilitation: A randomized controlled study.

BACKGROUND: Isometric strengthening has been rarely studied in patients with coronary heart disease (CHD), mainly because of possible potential side effects and lack of appropriate and reliable devices. OBJECTIVE: We aimed to compare 2 different modes of resistance training, an isometric mode with the Huber Motion Lab (HML) and traditional strength training (TST), in CHD patients undergoing a cardiac rehabilitation program. DESIGN: We randomly assigned 50 patients to HML or TST. Patients underwent complete blinded evaluation before and after the rehabilitation program, including testing for cardiopulmonary exercise, maximal isometric voluntary contraction, endothelial function and body composition. RESULTS: After 4 weeks of training (16 sessions), the groups did not differ in body composition, anthropometric characteristics, or endothelial function. With HML, peak power output (P=0.035), maximal heart rate (P<0.01) and gain of force measured in the chest press position (P<0.02) were greater after versus before training. CONCLUSION: Both protocols appeared to be well tolerated, safe and feasible for these CHD patients. A training protocol involving 6s phases of isometric contractions with 10s of passive recovery on an HML device could be safely implemented in rehabilitation programs for patients with CHD and improve functional outcomes.

Medical and pharmacological approach to adjust the salbutamol anti-doping policy in athletes.

BACKGROUND: Salbutamol abuse detection by athletes is based on a urinary upper threshold defined by the World Anti-Doping Agency (WADA). However, this threshold was determined in healthy, untrained individuals and after a dose of salbutamol inhaled that might not really mirror the condition of asthmatic athletes and the experts's guidelines for asthma management. We aimed to revise this threshold in accordance with recommended clinical practice (that appear to be different from the actual WADA recommendation) and in exercise conditions. METHODS: For the present open-label design study, we included 12 trained male cyclists (20 to 40 y/o) with asthma. Differently from the previous pharmacokinetic study supporting the actual salbutamol urinary upper threshold, we decided to administer a close to recommended clinical practice daily dose of 3x200 µg.d(-1) inhaled salbutamol (instead of 1600 µg.d(-1) as authorized by the anti-doping policy). Urine salbutamol concentration was quantified by liquid chromatography-tandem ion trap mass spectrometry and corrected for urine density, at rest and after a 90-min cycling effort at 70-80 % of the maximal aerobic power. RESULTS: The maximum urine salbutamol concentration value peaked after the cycling effort and was 510 ng.mL(-1). That is twice lower than the actual WADA threshold to sanction salbutamol abuse, this "legal" threshold being based on pharmacokinetic data after a daily dose that is 8 fold the total dose sequentially administrated in our study. Considering its 95 % confidence interval, this threshold value could be more stringent. CONCLUSION: By using conditions in accordance with the experts' clinical and safety guidelines for asthma management in athletes undergoing an intense exercise bout, our study suggests that the urine salbutamol concentration threshold could be lowered to redefine the rule supporting the decision to sanction an athlete for salbutamol abuse.

Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis.

This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n=18 in the meta-analysis). Most studies used a multicomponent exercise training (n=13) as intervention; the control group was often a usual care (n=10) or a socially-active (n=8) group. Exercise did not reduce global levels of BPSD (n=4. Weighted mean difference -3.884; 95% CI -8.969-1.201; I(2)=69.4%). Exercise significantly reduced depression levels in PWD (n=7). Standardized mean difference -0.306; 95% CI -0.571 to -0.041; I(2)=46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p=0.038), multicomponent training (p=0.056), social control group (p=0.08), and low risk of attrition bias (p=0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD.

Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 µg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).

Whole-body strength training using a Huber Motion Lab in coronary heart disease patients: safety, tolerance, fuel selection, and energy expenditure aspects and optimization.

OBJECTIVE: The aim of this study was to investigate safety, tolerance, relative exercise intensity, and muscle substrate oxidation during sessions performed on a Huber Motion Lab in coronary heart disease patients. DESIGN: After an assessment of Vo2 peak, 20 coronary heart disease patients participated in two different exercises performed in random order at 40% and 70% (W40 and W70) of the maximal isometric voluntary contraction. RESULTS: No significant arrhythmia or abnormal blood pressure responses occurred during either session, and no muscle soreness was reported within 48 hrs posttest. The authors found a difference between W40 and W70 sessions for mean (standard deviation) ventilation (25.1% [8%] and 32.1% [9%] of maximal ventilation, respectively; P = 0.04) and a small difference for mean (standard deviation) heart rate (73 [7] and 79 [8] beats/min, respectively; P < 0.01). When compared with the W40, the W70 was associated with higher active energy expenditure (2.4 [0.6] and 3.1 [0.9] Kcal/min, respectively; P < 0.0001) and a similar mean (standard deviation) oxygen uptake (5.5 [1] and 6.6 [1] ml/min per kilogram, respectively; P = 0.07). The qualitative percentages of carbohydrates and lipids oxidized were 71% and 29%, respectively, at W40 and 91% and 9%, respectively, at W70. CONCLUSIONS: Both protocols, which consisted of repeating 6-sec phases of contractions with 10 secs of passive recovery on the Huber Motion Lab, seemed to be well tolerated, safe, and feasible in this group of coronary heart disease patients.

Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction.

Facioscapulohumeral muscular dystrophy (FSHD), the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes. One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances. We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper-zinc-dependent superoxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (T(LimQ)) and maximal voluntary contraction (MVC(Q)) values (rho=0.79, P=0.003; rho=0.62, P=0.05, respectively). The plasma concentration of oxidized glutathione was negatively correlated with the T(LimQ), MVC(Q) values, and the 2-min walk distance (MWT) values (rho=-0.60, P=0.03; rho=-0.56, P=0.04; rho=-0.93, P<0.0001, respectively). Our data characterized oxidative stress in patients with FSHD and demonstrated a correlation with their peripheral skeletal muscle dysfunction. They suggest that antioxidants that might modulate or delay oxidative insult may be useful in maintaining FSHD muscle functions.

The interest of gait markers in the identification of subgroups among fibromyalgia patients.

BACKGROUND: Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. METHODS: A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. RESULTS: SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status. CONCLUSION: Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.

Physical activity and sarcopenia.

Physical activity can be a valuable countermeasure to sarcopenia in its treatment and prevention. In considering physical training strategies for sarcopenic subjects, it is critical to consider personal and environmental obstacles to access opportunities for physical activity for any patient with chronic disease. This article presents an overview of current knowledge of the effects of physical training on muscle function and the physical activity recommended for sarcopenic patients. So that this countermeasure strategy can be applied in practice, the authors propose a standardized protocol for prescribing physical activity in chronic diseases such as sarcopenia.

N-acetylcysteine protects against bupivacaine-induced myotoxicity caused by oxidative and sarcoplasmic reticulum stress in human skeletal myotubes.

BACKGROUND: Local anesthetics offer the benefits of extended analgesia with greater patient satisfaction and faster rehabilitation compared with intravenous morphine. These benefits, however, can be offset by adverse iatrogenic muscle pain. Here, the authors investigate the mechanisms of local anesthetic-induced myotoxicity and assess the protective effect of N-acetylcysteine. METHODS: The authors used primary cell cultures of human skeletal muscle myoblasts to study local anesthetic adverse effects. Production of reactive oxygen species was investigated in human skeletal myotubes by fluorescence microscopy. Expression of sarcoplasmic/endoplasmic reticulum stress markers and induction of apoptosis were followed by immunofluorescence and Western blot analysis. Finally, the effect of N-acetylcysteine on bupivacaine-induced myotoxicity was investigated in vitro. RESULTS: Bupivacaine sequentially induced reactive oxygen species production, oxidative stress, sarcoplasmic/endoplasmic reticulum stress, and activation of caspases 9 and 7 in human differentiated myoblasts. These iatrogenic effects were prevented by N-acetylcysteine. CONCLUSIONS: The authors demonstrated a protective effect of N-acetylcysteine against bupivacaine-induced sarcoplasmic/endoplasmic reticulum stress and apoptosis in primary human skeletal muscle cell.