Muscular Impairment Research Articles

Cognitive and Behavioral Profile of Egyptian Children with Duchenne Muscular Dystrophy

Background Duchenne Muscular Dystrophy (DMD) is a progressive neuromuscular disorder that could be associated with cognitive and behavioral disorders. Aim To evaluate the cognitive abilities and behavioral disorders in children with DMD and possible relation to various clinical characteristics. Subjects and methods 50 boys with DMD aged 6–14 years and an age-matched 50 boys as a control were included in the study. Assessment of cognitive function was the done using Arabic version of Stanford Binet intelligence test fourth edition, and behavioral assessment was done using the Arabic version of child behavior checklist. Results There was statistically significant difference between both groups regarding the total as well as all subscales of IQ test, cases showed lower scores on total and subscales IQ in comparison to controls. There was statistically significant difference between the mean scores in cases and control in all scales; internalizing problems, externalizing problems, other problems, as well as the total score. More children in the clinical and borderline categories in all domains were observed in the cases as compared to the control group. Positive relation was detected between internalizing behavioral problems and ambulatory state, duration of disease, associated conditions and cognitive abilities. Also, positive relation was observed between IQ and ambulatory state. Conclusion Cognitive and behavioral problems are common in DMD. Cognitive impairment have an association with the progression of muscular deterioration and loss of ambulation. Internalizing problems are more common with prolonged duration of illness, loss of ambulation, presence of associated conditions and cognitive abilities.

Dyspnea assessment in myotonic dystrophy type 1

In myotonic mystrophy type 1 (DM1), combining respiratory symptom screening and respiratory function testing, is crucial to identify the appropriate time for ventilatory support initiation. Dyspnea has been little investigated in DM1. To provide a multidimensional description of dyspnea, questionnaires assessing dyspnea were administered to 34 consecutive adult patients with DM1 (median (25th-75th centile) age of 36 (28–49), Vital Capacity (VC) of 74 (64–87)% of predicted value). Dyspnea scores were low whatever the questionnaire used: Multidimensional Dyspnea Profile score of 2(0–4.7)/50 for dyspnea sensory descriptor and of 0 (0–4.7)/60 for the emotional descriptor, Visual Analogue Scale score of 0 (0–0)/10 in sitting and supine position and Borg score after six-minute walk test (6MWT) of 2.2 (1.8–4.2)/10. Eleven patients (32%) reported disabling dyspnea in daily living (modified Medical Research Council (mMRC) score ≥ 2). In comparison with patients with mMRC score < 2, patients with mMRC score ≥ 2 had a more severe motor handicap (Muscular Impairment Rating score of 4.0 (4.0–4.0) vs 3.0 (2.0–3.5), p<0.01), a lower 6MWT distance (373 (260–424) vs 436 (346–499)m, p = 0.03) and a lower VC (64 (48–74)% vs 75 (69–89)%, p = 0.02). These data suggest that the mMRC scale might be an easy-to-use and useful tool to assess dyspnea in daily living in DM1 patients. However, the interest of integrating the mMRC dyspnea scale in clinical practice to guide therapeutic management of DM1 patients remains to be assessed in further studies.

Myotonic dystrophy type 1: A comparison between the adult- and late-onset subtype.

Although the extent of muscle weakness and organ complications has not been well studied in patients with late-onset myotonic dystrophy type 1 (DM1), adult-onset DM1 is associated with severe muscle involvement and possible life-threatening cardiac and respiratory complications. In this study we aimed to compare the clinical phenotype of adult-onset vs late-onset DM1, focusing on the prevalence of cardiac, respiratory, and muscular involvement. Data were prospectively collected in the Dutch DM1 registry. Two hundred seventy-five adult-onset and 66 late-onset DM1 patients were included. Conduction delay on electrocardiogram was present in 123 of 275 (45%) adult-onset patients, compared with 24 of 66 (36%) late-onset patients (P = .218). DM1 subtype did not predict presence of conduction delay (odds ratio [OR] 0.706; confidence interval [CI] 0.405 to 1.230, P=.219). Subtype did predict indication for noninvasive ventilation (NIV) (late onset vs adult onset: OR, 0.254; CI, 0.104 to 0.617; P=.002) and 17% of late-onset patients required NIV compared with 40% of adult-onset patients. Muscular Impairment Rating Scale (MIRS) scores were significantly different between subtypes (MIRS 1 to 3 in 66% of adult onset vs 100% of late onset [P < .001]), as were DM1-activC scores (67 ± 21 in adult onset vs 87 ± 15 in late onset; P < .001). Although muscular phenotype was milder in late-onset compared with adult-onset DM1, the prevalence of conduction delay was comparable. Moreover, subtype was unable to predict the presence of cardiac conduction delay. Although adult-onset patients had an increased risk of having an NIV indication, 17% of late-onset patients required NIV. Despite different muscular phenotypes, screening for multiorgan involvement should be equally thorough in late-onset as in adult-onset DM1.

Psychological Wellbeing and Perceived Fatigue in Competitive Athletes after SARS-CoV-2 Infection 2 Years after Pandemic Start: Practical Indications

The COVID-19 pandemic deeply affected sports and athletes, influencing performance and psychological wellbeing. In order to provide useful guidelines for coaches, a web-based survey was conducted. Three web-based questionnaires were administered during the last phase of the Omicron wave to a total of 204 Italian athletes (age 24.96 ± 9.82): an informative questionnaire to collect sociodemographic data and infection symptoms information, the Fatigue Severity Scale (FSS) and the General Health Questionnaire-12 (GHQ-12). No differences between infection sequels of different variant typologies were found over the long term after the infection. The most frequently declared symptoms included cough (50%), muscular skeletal impairments (48%) fatigue (43%) and fever (43%). Results showed that female athletes have a higher risk of developing post-COVID-19 symptoms, GHQ-12 worse results (p = 0.005) and greater fatigue (p = 0.0002) than males. No significant difference in infection incidence between high- and low-level athletes was found. Endurance athletes showed greater perceived fatigue than anaerobic sports athletes (p = 0.045). Conclusions: These results suggested the need for specific approaches and continuous updating to differentiate training programs for different athletes during the return to play. Medical controls and daily monitoring of athletes of all levels after the infection could be advisable.

Shedding light on motor premanifest myotonic dystrophy type 1: A molecular, muscular and central nervous system follow-up study.

Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease that is characterized by heterogeneous manifestations. Although muscular impairment is central to DM1, a premanifest DM1 form has been proposed for those characterized by the absence of muscle signs in precursory phases. Nevertheless, subtle signs and/or symptoms related to other systems, such as the central nervous system (CNS), may emerge and progress gradually. This study aimed to validate the premanifest DM1 concept and to characterize and track affected individuals from a CNS centred perspective. Retrospective data of 120 participants (23 premanifest DM1, 25 manifest DM1 and 72 healthy controls) were analysed transversally and longitudinally (over 11.17 years). Compiled data included clinical, neuropsychological and neuroradiological (brain volume and white matter lesion, WML) measures taken at two time points. Manifest DM1 showed significantly more molecular affectation, worse performance on neuropsychological domains, lower grey and white matter volumes and a different pattern of WMLs than premanifest DM1. The latter was slightly different from healthy controls regarding brain volume and WMLs. Additionally, daytime sleepiness and molecular expansion size explained 50% of the variance of the muscular deterioration at follow-up in premanifest individuals. Premanifest DM1 individuals showed subtle neuroradiological alterations, which suggests CNS involvement early in the disease. Based on follow-up data, a debate emerges around the existence of a 'non-muscular DM1' subtype and/or a premanifest phase, as a precursory stage to other DM1 manifestations.

P.207 Muscle magnetic resonance imaging in Myotonic dystrophy type 1: Longitudinal study for 5 years

Myotonic dystrophy type 1 is the most common genetic muscle disease in adults, caused by increased expansion of CTG repeats in the DMPK gene. It is characterized by progressive distal dominant muscle weakness and myotonia. The aim of this study was to evaluate objective longitudinal changes in the muscle magnetic resonance imaging in DM1 patients over five years. Eighteen genetically diagnosed DM1 patients were enrolled at baseline. The mean age was 44.86±9.83, mean CTG repeat length was 465±328.86 and a disease duration of 18.29±9.43 years. The baseline motor function such as medical research council sum score, Muscular impairment rating scale and 6-minute walk test were evaluated at the baseline and after 5 years of follow up. The pulmonary function and serum creatine kinase levels were also evaluated. The muscle magnetic resonance imaging was performed at baseline and after 5 years. The individual muscles were semi-quantitatively graded using five-point Mercuri scores. The thirteen upper muscle groups and twenty one lower limb muscles were evaluated. The lower muscle groups including gluteus muscles. The fatty infiltrative changes progressed after 5 years of follow up, with significant score changes were most prominently observed in lower limb muscles including gastrocnemius, soleus, tibialis anterior, gastrocnemius and tensor fascia latae muscles. Among upper limb muscles, latissimus dorsi showed most significant fatty infiltrative changes, followed by serratus and rhomboid muscles. Bases on the longitudinal follow up of the muscle MRI, DM1 showed significant deterioration in the lower limb muscles, with prominent changes in the crural muscles. This is the first longitudinal muscle MRI study and more studies are warranted to understand muscle degeneration in DM1.

P.205 Utility of electrical bioimpedance as a biomarker in myotonic dystrophy type I

Myotonic dystrophy type 1 (DM1) is frequently associated with endocrinopathies. Body composition analysis by electrical bioimpedance study is useful in the nutritional assessment of these patients. The aim of this study is to investigate its usefulness as a biomarker of clinical progression/severity in DM1. We carried out a cross-sectional study of 47 patients with DM1 attended in the last year who underwent impedancemetry with the InBody S10 device for segmental multifrequency analysis. Muscle weakness was classified according to severity using the muscular impairment rating scale (MIRS). 18 men and 29 women were evaluated. Mean age was 46.11 years. By means of Spearman's Rho correlation, a highly statistically significant concordance was identified between the MIRS scale and the global phase angle (PA) at 50 kHz (p 0.000 and R -0.717) and also with the skeletal muscle mass index (SMMI) (p 0.000 and R -0.549). However, no relationship was observed between MIRS with classical nutritional indicators such as BMI or percentage weight loss. In logistic regression models, PA and SMMI adjusted by age and sex decrease statistically significantly as muscle weakness progresses with high explanatory value. There is a highly significant correlation between clinical severity measured by the MIRS scale and PA and SMMI. PA and SMMI are more sensitive, early and constant as a marker of muscle deterioration than any of the GLIM phenotypic criteria for the diagnosis of malnutrition that are usually related to muscle weakness, thus postulating themselves as a possible useful biomarker of progression in DM1.

Evaluation Of Valid VO2max Criteria For Graded Exercise Testing In Cancer Survivors

INTRO: Using a metabolic cart (met cart) to obtain an individual's maximal oxygen consumption (VO2max) is considered the gold standard method of measurement. An accurate VO2max value is important in every population for individualized exercise prescriptions (ExRx), but specifically within the cancer population due to treatment status. Certain criteria must be met for a value to be considered a true VO2max. Utilizing gas analysis to track the changing respiratory exchange ratio (RER) and achieving >1.10 is the best criteria to determine if true max was obtained. Other maximal criteria such as 85% of heart rate max (HR) using the Tanaka formula and rate of perceived exertion (RPE) of >7 on the Modified Borg Scale also have the potential to be used as maximal criteria eliminating the need for a met cart. It is unknown if HR and RPE can be used independently as valid termination criteria in the cancer population during VO2max assessments. PURPOSE: To evaluate the frequency of achieving VO2max as determined by RER and alternate maximal criteria using HR and RER in a sample of cancer survivors. METHODS: Forty cancer survivors participated in the study. Subjects performed one GXT per week for three weeks using gas analysis. RER, HR, and RPE values were recorded. A total of 111 GXTs were used for data analysis. A Cochran’s Q test was used to determine if there were differences in the frequency of successful achievement of RER, HR, and RPE maximal criteria during the GXTs. RESULTS: Maximal criteria was successfully met in 95, 89, and 102 GXTs when evaluating RER, HR, and RPE, respectively. No significant differences occurred in the achievement of max between RER, HR, and RPE criteria (p < 0.061). CONCLUSION: The findings from this data set suggest that HR and RPE may be valid and suitable criteria for termination of a GXT if obtaining an RER value is not feasible or clinically practical. Cancer survivors experience toxicities such as skin irritation, muscular impairments, balance issues, peripheral neuropathy, and/or cancer related fatigue, making use of a met cart and mask potential impediments to maximal performance. Elimination of the met cart may allow the individual to advance further into a GXT leading to more accurate VO2max values and thus more accurate ExRx in the cancer population.

Relationship Between Multiple Sclerosis Severity and Fear of Falling With Mediating Roles of Disability, Cognitive Factors, and Physical Factors Among Patients With MS

Background: Fear of falling (FoF) is a permanent concern and may limit daily activities and diminish confidence in balance abilities leading to muscular deterioration, a sedentary lifestyle, and reduced quality of life. The present study aimed to investigate the relationship between multiple sclerosis severity and FoF with mediating roles of disability, cognitive factors, and physical factors among patients with multiple sclerosis (MS). Methods: This research was a correlational study based on path analysis. The statistical population consisted of all patients with MS who visited the neurology centers of hospitals in Sari, Iran. A total of 200 MS patients were selected as the sample using multistage random sampling. Two hospitals were selected from the hospitals of Sari city and the research sample was selected from the neurology centers of these hospitals. The research instruments included the falls efficacy scale-international, the MS severity scale, the expanded disability status scale, the cognitive factors questionnaire, and the MOS 36-item short-form health survey. The data were analyzed by structural equation modeling in AMOS and SPSS software, version 25. Results: The results of structural equation modeling demonstrated that the proposed model fitted the data. FoF had positive significant relationships with MS severity and disability. MS severity and FoF had negative significant relationships with physical factors (P&lt;0.01). The direct relationship between MS severity and cognitive factors was insignificant and excluded from the model. The study findings confirmed the relationship between MS severity and FoF mediated by disability and physical factors in patients with MS (P&lt;0.01). Conclusion: The frequency of FoF was much higher among patients with higher MS severity. Considering the consequences of the FoF among patients with MS, it is recommended that consultation services be provided to patients with MS at healthcare centers to improve their health and activity and reduce their FoF.

Relationship between muscular impairment and psychological health with lower extremity functions in patients with transtibial amputation.

To determine the relationship of muscular impairment and psychological health with lower extremity functions in patients with transtibial amputation. The correlational study was conducted from March to September 2021 at the Fauji Foundation Hospital, Rawalpindi, Pakistan, and comprised male patients with transtibial amputation. Data was collected using the depression anxiety stress scale and the lower extremity functional scale. The correlation of muscular impairment and psychological health with lower extremity functions was determined. Data was analysed using SPSS 21. There were 85 male patients with a mean age of 53.74±11.30 years. There was weak iliopsoas muscle strength 4.64±0.50 and reduced muscle length of hamstrings 67.00±6.41 on the affected side. There was non-significant correlation in muscle atrophy of both amputated limb (p=0.82) and non-amputated limb (p=0.58) with lower extremity function. Significant inverse correlation was present between depression, anxiety and stress (p=0.001) with lower extremity function. Weak iliopsoas muscle strength and tight hamstrings were observed on the amputated side. Muscle atrophy was more in non-amputated limb than amputated limb. There was significant inverse correlation of depression, anxiety and stress with lower extremity function.

Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19

BackgroundThe mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment.MethodsPatients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD).ResultsSixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO < 80%, 90% had CT-scan abnormalities; 40% had sarcopenia/pre-sarcopenia and 31% had symptoms of PTSD. Cluster analysis identified a group of patients (n = 18, 30.5%) with a severe persistent (SP) respiratory impairment (DLCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management.Conclusions and clinical implicationWe identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia.Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840

Arthrogenic Muscle Inhibition: Best Evidence, Mechanisms, and Theory for Treating the Unseen in Clinical Rehabilitation.

Arthrogenic muscle inhibition (AMI) impedes the recovery of muscle function following joint injury, and in a broader sense, acts as a limiting factor in rehabilitation if left untreated. Despite a call to treat the underlying pathophysiology of muscle dysfunction more than three decades ago, the continued widespread observations of post-traumatic muscular impairments are concerning, and suggest that interventions for AMI are not being successfully integrated into clinical practice. To highlight the clinical relevance of AMI, provide updated evidence for the use of clinically accessible therapeutic adjuncts to treat AMI, and discuss the known or theoretical mechanisms for these interventions. PubMed and Web of Science electronic databases were searched for articles that investigated the effectiveness or efficacy of interventions to treat outcomes relevant to AMI. 122 articles that investigated an intervention used to treat AMI among individuals with pathology or simulated pathology were retrieved from 1986 to 2021. Additional articles among uninjured individuals were considered when discussing mechanisms of effect. AMI contributes to the characteristic muscular impairments observed in patients recovering from joint injuries. If left unresolved, AMI impedes short-term recovery and threatens patients' long-term joint health and well-being. Growing evidence supports the use of neuromodulatory strategies to facilitate muscle recovery over the course of rehabilitation. Interventions should be individualized to meet the needs of the patient through shared clinician-patient decision-making. At a minimum, we propose to keep the treatment approach simple by attempting to resolve inflammation, pain, and effusion early following injury.

Itavastatin and resveratrol increase triosephosphate isomerase protein in a newly identified variant of TPI deficiency.

ABSTRACTTriosephosphate isomerase (TPI) deficiency (TPI Df) is an untreatable glycolytic enzymopathy that results in hemolytic anemia, progressive muscular impairment and irreversible brain damage. Although there is a ‘common’ mutation (TPIE105D), other pathogenic mutations have been described. We identified patients who were compound heterozygous for a newly described mutation, TPIQ181P, and the common TPIE105D mutation. Intriguingly, these patients lacked neuropathy or cognitive impairment. We then initiated biochemical and structural studies of TPIQ181P. Surprisingly, we found that purified TPIQ181P protein had markedly impaired catalytic properties whereas crystallographic studies demonstrated that the TPIQ181P mutation resulted in a highly disordered catalytic lid. We propose that genetic complementation occurs between the two alleles, one with little activity (TPIQ181P) and one with low stability (TPIE105D). Consistent with this, TPIQ181P/E105D fibroblasts exhibit a significant reduction in the TPI protein. These data suggest that impaired stability, and not catalytic activity, is a better predictor of TPI Df severity. Lastly, we tested two recently discovered chemical modulators of mutant TPI stability, itavastatin and resveratrol, and observed a significant increase in TPI in TPIQ181P/E105D patient cells.

The characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 patients especially concerning swallowing function evaluated by endoscopy

ObjectiveThe objectives of the study were to clarify the characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 (DM1) patients, and to investigate the relationship between the development of pneumonia and the DM1 patient's background, especially concerning swallowing function evaluated by endoscopy. MethodsThe subjects were 88 DM1 patients who underwent swallowing function evaluation. The severity of disease in DM1patients was assessed based on the muscular impairment rating scale (MIRS), and the number of CTG repeats. Patients were divided into two groups; those who developed aspiration pneumonia within two years after swallowing assessment and those who did not develop aspiration pneumonia. Swallowing function was assessed using the food intake level scale (FILS), repetitive saliva swallowing test (RSST), the modified water swallowing test (MWST), and the Hyodo score. ResultsOnset of pneumonia within two years of assessment was observed in 22 cases (25%). Age, FILS, and Hyodo score were significantly different between pneumonia and non-pneumonia groups. There was a significant difference in swallowing function tests such as FILS, RSST, and Hyodo score between males and females. The Hyodo score cutoff value for predicting pneumonia within two years was determined by ROC analysis. A cutoff value of 6 was found to have a sensitivity of 0.545 and a specificity of 0.833 (area under the curve=0.722). ConclusionIt is important to evaluate the swallowing function of DM1 patients by endoscopy to prevent aspiration pneumonia. In addition, male patients are more likely to deteriorate in swallowing function and should be carefully monitored.

Alterations in biogenic amines levels associated with age-related muscular tissue impairment in Drosophila melanogaster

While holding on youth may be a universal wish, aging is a natural process associated with physical and physiological impairment in living organisms. Drosophila provides useful insights into aging-related events. Hence, this study was conducted to investigate the age-related changes in muscle function and architecture in relation to the biogenic amine titers. To achieve this aim, visceral and skeletal muscles performance was tested in newly-eclosed, sexually mature and old adult flies using climbing and gut motility assays. In addition, age-related ultrastructural alterations of muscular tissue were observed using transmission electron microscopy (TEM). The titer of selected biogenic amines was measured using high-performance liquid chromatography (HPLC). The results demonstrated that old flies were dramatically slower in upward movement than either newly-eclosed or sexually mature flies. Similarly, gut contraction rate was significantly lower in old flies than the sexually mature, although it was markedly higher than that in the newly-eclosed flies. In TEM examination, there were several ultrastructural changes in the midgut epithelium, legs and thorax muscles of old flies. Regarding biogenic amine titers, the old flies had significantly lower concentrations of octopamine, dopamine and serotonin than the sexually mature. We concluded that aging has adverse effects on muscular system function and ultrastructure, synchronized with biogenic amine titers changes. Our results highlighted the need for more researches on therapeutics that may balance the levels of age-related alterations in biogenic amines.

Abstract EP18: Cardiopulmonary Testing In Long Covid Versus Non-CovidPatients With Undifferentiated Dyspnea On Exertion

Background: COVID-19 reveals new manifestations not only in the acute phase but also in the long term. The latter is what has been termed as ‘post acute sequelae of SARS-CoV-2 infection’ (PASC) — or “long COVID”— with dyspnea as one of its hallmarks. Cardiopulmonary stress testing (CPET) is increasingly being used to better evaluate such patients. Objective: To compare CPET findings of long COVID patients versus non-COVID patients with undifferentiated dyspnea on exertion seen at Mayo Clinic. Methods: A cohort study was carried out using Mayo Clinic’s exercise testing database. The study group included 77 PASC patients confirmed by a positive antigen or PCR test with no prior history of heart or lung disease. PASC patients were compared to 766 non-COVID patients with unspecified dyspnea without known diagnosis of cardiac or pulmonary disease. ANOVA according to the general linear model and Pearson’s Chi square were used for the bivariate analysis of the quantitative and categorical variables, respectively. Analyses were controlled for age, sex, and beta blocker use as appropriate. Both HR and SBP at rest and peak exercise were significantly different between groups, although the absolute differences were small. Results: Compared with the control group, the post-COVID patients were younger (mean age 47 SD ±14.9 years versus 50.5 SD ±10.1 years) and more likely to be female (70.1% (54 of 77) vs 57.6% (441 of 766)). Although there were many significant differences in the CPET results, the most outstanding were a lower FAC (73 SD ±19.4% vs 85.2 SD ±20.8%) and peak VO2 (22 SD ±6.4 ml/kg/min vs 25.8 SD ±7.37 ml/kg/min) in the study group (p&lt;.0001). Also, CNS changes during CPET were reported at higher rates (19.5% (15 of 77) vs 11.4% (87 of 766)) while dyspnea at lower rates (55.8% (43 of 77) vs 65.7% (503 of 766)) in post-COVID patients (p=0.02). When adjusting for age and sex, weight was significantly higher in the study group (p=0.03) although the absolute difference was modest and BMI remained not significant. PFTs did not suggest any pulmonary abnormalities. Conclusions: We identified a high rate of severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Pre-exercise PFTs and absence of objective respiratory limitation during CPET argue against a primary pulmonary cause of the observed limitations, though evaluation of cardiac, autonomic, and muscular impairment is pending. Further studies are warranted to untangle the physiologic abnormalities responsible for these observations.

The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice.

Sarcopenia is prevalent as the aging population grows. Therefore, the need for supplements for the elderly is increasing. This study aimed to investigate the efficacy and mechanism of a Panax ginseng berry extract (GBE) and soluble whey protein hydrolysate (WPH) mixture on a sarcopenia-related muscular deterioration in aged mice. Ten-month-old male C57BL/6J mice were administered three different doses of the GBE + WPH mixture for 8 weeks; 700 mg/kg, 900 mg/kg, and 1100 mg/kg. Grip strength, serum inflammatory cytokines level, and mass of muscle tissues were estimated. The deteriorating function of aging muscle was investigated via protein or gene expression. Grip strength and mass of three muscle tissues were increased significantly in a dose-dependent manner, and increased anti-inflammatory cytokine alleviated systemic inflammatory state. The mixture resolved the imbalance of muscle protein turnover through activation of the PI3K/Akt pathway and increased gene expression of the muscle regeneration-related factors, while decreasing myostatin, which interferes with muscle protein synthesis and regeneration. Furthermore, we confirmed that increased mitochondria number in muscle with the improvement of mitochondrial biogenesis. These physiological changes were similar to the effects of exercise.

Do We Have Good Activity Indices in Systemic Sclerosis?

No fully validated index is available for assessing overall disease activity in systemic sclerosis (SSc). To estimate the effect of disease activity as measured by different disease activity indices on the risk of subsequent organ damage. The European Systemic sclerosis study group activity index (EScSG AI), the European Scleroderma Trials and Research Group Activity Index (r-EUSTAR AI), 12 point activity index proposed by Minier (12point AI) were calculated for 91 patients; the CRISS (The Composite Response Index for Systemic Sclerosis) for patients included after 2016. Data were analysed by parametric and non-parametric tests and logistic regression. EscSG AI, r-EUSTAR AI and 12point AI correlated with lung involvement. EScSG AI and r-EUSTAR AI correlated with diffuse skin involvement. EscSG AI correlated with digital ulcers and diffuse cutaneous involvement and r-EUSTAR AI with a renal crisis. Bivariate analysis showed an inverse correlation between the three disease activity scores and forced vital capacity (FVC) (p<0.001) and diffusing capacity for carbon monoxide (DLCO) (p<0.001) and positive correlation with pulmonary fibrosis (p<0.001), modified Rodnan skin score (mRSS) (p<0.001), health assessment questionnaire (HAQ) (p<0.001), systolic pulmonary pressure (sPAP) (p<0.001), C-reactive protein (CRP) (p<0.001) and capillaroscopy scoring (p<0.001) at both baseline visit and the 3-year follow-up visit. Logistic regression revealed that baseline EScSG AI adjusted for gender and age and that baseline 12-point AI both adjusted and unadjusted predicted worse skin involvement at 3-year follow-up; while adjusted EScSG AI predicted decreasing DLCO. Also, 12-point AI predicted a decline of FVC and higher HAQ scores at 3-year follow up; while baseline r-EUSTAR AI was able to predict muscular deterioration, decline of FVC and the increase of HAQ score during 3 years of following. An active disease according to EScSG AI at first visit predicted progression of joint involvement while an active disease at baseline showed by r- EUSTAR AI predicted muscular deterioration, FVC and DLCO worsening, as well as an increase in HAQ score during the follow-up period. r-EUSTAR AI was the only score to predict the decrease of FVC in a multiple regression prediction model (OR= 1.306 (1.025, 1.665), p=0.31) while baseline EScSG AI best predicted worsening of DLCO (OR=1.749 (1.104, 2.772), p=0.017). Our study could not establish a gold standard to assess disease activity in SSc; especially EscSG AI and r-EUSTAR AI could quantify and predict major organ involvement in daily practice. CRISS can be useful as an outcome measure for patients with short disease duration included in clinical studies.

Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts.

Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to CTNS mutations. Recent research data in the field have demonstrated abnormal mineral regulation, intrinsic bone defects, cysteamine toxicity, muscle wasting and, likely interleukin-1-driven inflammation in the setting of CMBD. Here we summarize these new pathophysiological deregulations and discuss the crucial interplay between bone and muscle in INC. In future, vitamin D and/or biotherapies targeting the IL1β pathway may improve muscle wasting and subsequently CMBD, but this remains to be proven.

Free Fatty Acid Impairs Myogenic Differentiation through the AMPKα-MicroRNA 206 Pathway.

The activity of AMP-activated protein kinase α (AMPKα) is reduced in type 2 diabetes, and type 2 diabetes is associated with muscular atrophy. To date, there is little known about the mechanism by which free fatty acid (FFA) participates in muscular impairment. The purpose of the present study was to explore whether FFA damages myogenesis through the AMPKα-histone deacetylase 4 (HDAC4)-microRNA 206 (miR-206) pathway. The results showed that 1 mM FFA produced lipid accumulation, significantly impaired the insulin signaling pathway, and decreased the myogenic differentiation of C2C12 myoblast cells. FFA reduced the LKB1-AMPKα pathway, and the activation of AMPKα rescued the myogenic impairment caused by FFA (P < 0.05). AMPKα promoted myogenesis by regulating the expression of miR-206 through HDAC4 (P < 0.05) and affected the cell cycle and cell proliferation to promote myogenesis by regulating miR-206 and miR-206's target cyclin D1 gene. In addition, AICAR (5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside) and HDAC4 small interfering RNA (siRNA) promoted myogenic differentiation compared with the FFA group; however, this positive effect was significantly downregulated after transfection with the miR-206 inhibitor. In summary, AMPKα plays positive roles in myogenic differentiation and myogenesis, and FFA decreased myogenic differentiation and myotube formation through the AMPKα-HDAC4-miR-206 pathway.