Profound cellular defects attribute to muscular pathogenesis in the rhesus monkey model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutations in the DMD gene. Muscle fibers rely on the coordination of multiple cell types for repair and regenerative capacity. To elucidate the cellular and molecular changes in these cell types under pathologic conditions, we generated a rhesus monkey model for DMD that displays progressive muscle deterioration and impaired motor function, mirroring human conditions. By leveraging these DMD monkeys, we analyzed freshly isolated muscle tissues using single-cell RNA sequencing (scRNA-seq). Our analysis revealed changes in immune cell landscape, a reversion of lineage progressing directions in fibrotic fibro-adipogenic progenitors (FAPs), and TGF-ß resistance in FAPs and muscle stem cells (MuSCs). Furthermore, MuSCs displayed cell-intrinsic defects, leading to differentiation deficiencies. Our study provides important insights into the pathogenesis of DMD, offering a valuable model and dataset for further exploration of the underlying mechanisms, and serves as a suitable platform for developing and evaluating therapeutic interventions.

Two Novel Variants of the CAPN3 Gene in Chinese Patients with Limb-Girdle Muscular Dystrophy Recessive 1.

INTRODUCTION: Recessive mutations in the CAPN3 gene can lead to limb-girdle muscular dystrophy recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. METHODS: We performed targeted next-generation sequencing of all exons of the CAPN3 gene in 4 patients with sporadic limb-girdle muscular dystrophy (LGMD) and further analyzed the effects of the novel identified variant using various software tools. RESULTS: We found 5 variants in CAPN3 gene in 4 patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. DISCUSSION: Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

Exploring neuronal mechanisms of osteosarcopenia in older adults.

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight-bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing-related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults.

Skeletal and Non-skeletal Phenotypes in Children with Osteogenesis Imperfecta.

Although fractures are the defining characteristic of osteogenesis imperfecta (OI), the disorder affects many tissues. Here we discuss three facets of the OI phenotype, skeletal growth and development, skeletal muscle weakness and the dental and craniofacial characteristics. Short stature is almost universal in the more severe forms of OI and is probably caused by a combination of direct effects of the underlying genetic defect on growth plates and indirect effects of fractures, bone deformities and scoliosis. Recent studies have developed OI type-specific growth curves, which allow determining whether a given child with OI grows as expected for OI type. Impaired muscle function is an important OI-related phenotype in severe OI. Muscles may be directly affected in OI by collagen type I abnormalities in muscle connective tissue and in the muscle-tendon unit. Indirect effects like bone deformities and lack of physical activity may also contribute to low muscle mass and function. Dental and craniofacial abnormalities are also very common in severe OI and include abnormal tooth structure (dentinogenesis imperfecta), malocclusion, and deformities in the bones of the face and the skull. It is hoped that future treatment approaches will address these OI-related phenotypes.

High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

Long-term prognosis of fatty-acid oxidation disorders in adults: Optimism despite the limited effective therapies available.

INTRODUCTION: Fatty-acid oxidation disorders (FAODs) are recessive genetic diseases. MATERIALS AND METHODS: We report here clinical and paraclinical data from a retrospective study of 44 adults with muscular FAODs from six French reference centers for neuromuscular or metabolic diseases. RESULTS: The study cohort consisted of 44 adult patients: 14 with carnitine palmitoyl transferase 2 deficiency (32%), nine with multiple acyl-CoA deficiency (20%), 13 with very long-chain acyl-CoA dehydrogenase deficiency (30%), three with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (7%), and five with short-chain acyl-CoA dehydrogenase deficiency (11%). Disease onset occurred during childhood in the majority of patients (59%), with a mean age at onset of 15 years (range = 0.5-35) and a mean of 12.6 years (range = 0-58) from disease onset to diagnosis. The principal symptoms were acute muscle manifestations (rhabdomyolysis, exercise intolerance, myalgia), sometimes associated with permanent muscle weakness. Episodes of rhabdomyolysis were frequent (84%), with a mean creatinine kinase level of 68,958 U/L (range = 660-300,000). General metabolic complications were observed in 58% of patients, respiratory manifestations in 18% of cases, and cardiological manifestations in 9% of cases. Fasting acylcarnitine profile was used to orient genetic explorations in 65% of cases. After a mean follow-up of 10 years, 33% of patients were asymptomatic and 56% continued to display symptoms after exercise. The frequency of rhabdomyolysis decreased after diagnosis in 64% of cases. CONCLUSION: A standardized register would complete this cohort description of muscular forms of FAODs with exhaustive data, making it possible to assess the efficacy of therapeutic protocols in real-life conditions and during the long-term follow-up of patients.

Glucocorticoid treatment increases cholesterol availability during critical illness: effect on adrenal and muscle function.

BACKGROUND: Hypocholesterolemia hallmarks critical illness though the underlying pathophysiology is incompletely understood. As low circulating cholesterol levels could partly be due to an increased conversion to cortisol/corticosterone, we hypothesized that glucocorticoid treatment, via reduced de novo adrenal cortisol/corticosterone synthesis, might improve cholesterol availability and as such affect adrenal gland and skeletal muscle function. METHODS: In a matched set of prolonged critically ill patients (n = 324) included in the EPaNIC RCT, a secondary analysis was performed to assess the association between glucocorticoid treatment and plasma cholesterol from ICU admission to day five. Next, in a mouse model of cecal ligation and puncture-induced sepsis, septic mice were randomized to receive either hydrocortisone (1.2 mg/day) (n = 17) or placebo (n = 15) for 5 days, as compared with healthy mice (n = 18). Plasma corticosterone, cholesterol, and adrenocortical and myofiber cholesterol were quantified. Adrenal structure and steroidogenic capacity were evaluated. Muscle force and markers of atrophy, fibrosis and regeneration were quantified. In a consecutive mouse study with identical design (n = 24), whole body composition was assessed by EchoMRI to investigate impact on lean mass, fat mass, total and free water. RESULTS: In human patients, glucocorticoid treatment was associated with higher plasma HDL- and LDL-cholesterol from respectively ICU day two and day three, up to day five (P < 0.05). Plasma corticosterone was no longer elevated in hydrocortisone-treated septic mice compared to placebo, whereas the sepsis-induced reduction in plasma HDL- and LDL-cholesterol and in adrenocortical cholesterol was attenuated (P < 0.05), but without improving the adrenocortical ACTH-induced CORT response and with increased adrenocortical inflammation and apoptosis (P < 0.05). Total body mass was further decreased in hydrocortisone-treated septic mice (P < 0.01) compared to placebo, with no additional effect on muscle mass, force or myofiber size. The sepsis-induced rise in markers of muscle atrophy and fibrosis was unaffected by hydrocortisone treatment, whereas markers of muscle regeneration were suppressed compared to placebo (P < 0.05). An increased loss of lean body mass and total and free water was observed in hydrocortisone-treated septic mice compared to placebo (P < 0.05). CONCLUSIONS: Glucocorticoid treatment partially attenuated critical illness-induced hypocholesterolemia, but at a cost of impaired adrenal function, suppressed muscle regeneration and exacerbated loss of body mass.

Blood Profiles of Community-Dwelling People with Sarcopenia: Analysis Based on the China Health and Retirement Longitudinal Study.

INTRODUCTION: Routine blood factors can be economical and easily accessible candidates for sarcopenia screening and monitoring. The associations between sarcopenia and routine blood factors remain unclear. This study aimed to examine sarcopenia and blood factor associations based on a nation-wide cohort in China. METHODS: A total of 1,307 participants and 17 routine blood indices were selected from two waves (year 2011 and year 2015) of the China Health and Retirement Longitudinal Study (CHARLS). The diagnosis of sarcopenia was based on the criteria proposed by the Asian Working Group for Sarcopenia (AWGS 2019). Generalized mixed-effects models were performed for association analyses. A logistic regression (LR) model was conducted to examine the predictive power of identifying significant blood factors for sarcopenia. RESULTS: A higher sarcopenia risk was cross-sectionally associated with elevated blood concentrations of high-sensitivity C-reactive protein (hsCRP) (OR = 1.030, 95% CI [1.007, 1.053]), glycated hemoglobin (HbA1c) (OR = 1.407, 95% CI [1.126, 1.758]) and blood urea nitrogen (BUN) (OR = 1.044, 95% CI [1.002, 1.089]), and a decreased level of glucose (OR = 0.988, 95% CI [0.979, 0.997]). A higher baseline hsCRP value (OR = 1.034, 95% CI [1.029, 1.039]) and a greater over time change in hsCRP within 4 years (OR = 1.034, 95% CI [1.029, 1.039]) were associated with a higher sarcopenia risk. A higher BUN baseline value was related to a decreased sarcopenia risk over time (OR = 0.981, 95% CI [0.976, 0.986]), while a greater over time changes in BUN (OR = 1.034, 95% CI [1.029, 1.040]) and a smaller over time change in glucose (OR = 0.992, 95% CI [0.984, 0.999]) within 4 years were also related to a higher sarcopenia risk. LR based on significant blood factors (i.e., hsCRP, HbA1c, BUN, and glucose), and sarcopenia status in year 2015 yielded an area under the curve of 0.859 (95% CI: 0.836-0.882). CONCLUSION: Routine blood factors involved in inflammation, protein metabolism, and glucose metabolism are significantly associated with sarcopenia. In clinical practice, plasma hsCRP, BUN, blood sugar levels, sex, age, marital status, height, and weight might be helpful for sarcopenia evaluation and monitoring.

Examination of Risk Factors Associated With Falls and Injurious Falls in People With Multiple Sclerosis: An Updated Nationwide Study.

OBJECTIVE: To provide an update on risk factors associated with falls and injurious falls among people with multiple sclerosis (PwMS) in the United States. DESIGN: Nationwide cross-sectional web-based survey. SETTING: Community setting. PARTICIPANTS: Adult PwMS (n=965). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants completed self-report surveys of demographics, clinical data, concerns about falling, occurrence of falls, factors associated with falls, and injurious falls in the past 6 months. Participants also completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures of depression, pain interference, and physical function, and the Fatigue Severity Scale. RESULTS: The most common self-reported factors associated with falls included personal factors such as poor balance (75%), muscle weakness (54%), and/or fatigue (35%), environmental factors such as general surface conditions (37%) and/or distraction (15%), and activities-related factors such as urgency to complete a task (35%) and/or multitasking (27%). Logistic regression analyses indicated that higher fatigue severity (OR=1.19, P<.01) and higher pain interference (OR=1.02, P<.01) were associated with higher odds of experiencing at least 1 fall. Any level of concern, even minimal concern about falling was also significantly associated with a higher odd of experiencing at least 1 fall (ORs range 2.78 - 3.95, all P<.01). Fair to very high concerns about falling compared with no concern about falling (ORs range=5.17 - 10.26, all P<.05) was significantly associated with higher odds of sustaining an injurious fall. CONCLUSIONS: Findings suggest falls prevention approaches in PwMS should be multifactorial and include personal, environmental, and activities-related factors. Particular attention on fatigue, pain, and concern about falling may be needed to reduce incidence of falls and injurious falls in this population.

Cardiovascular disease risk factors and frailty syndrome in community-dwelling older adults: Results from the Amirkola Health and Aging Project Cohort Study.

BACKGROUND: Early diagnosis and control of risk factors affecting frailty syndrome (FS) in older adults may lead to changes in the health/disease process, prevention of disability and dependency in the older adults, and reduction of health care costs and mortality rates. The aim of this study was to determine the predictive role of CVD risk factors and FS in community-dwelling older adults of Amirkola city in Iran. METHODS: This descriptive-analytic cross-sectional study is part of the second phase of the Amirkola Health and Aging Project (AHAP) cohort study conducted since 2011 on all individuals ≥ 60 years in the city of Amirkola in northern Iran. Totally, 1000 older adults were included in the study and divided into three groups: frail (n = 299), pre-frail (n = 455), and non-frail (n = 246) older adults. In the present study, age ≥ 60 years, female sex, fasting blood sugar (FBS) ≥ 126 mg/dl, affected diabetes mellitus (DM), body mass index (BMI) ≥ 27 kg/m², waist circumference (WC) or abdominal obesity > 102 cm in men and > 88 cm in women, low-density lipoprotein (LDL) > 100 mg/dl, triglyceride > 150 mg/dl, cholesterol > 200 mg/dl, high-density lipoprotein (HDL) < 40 mg/dl and blood pressure (BP) > 90/140 mmHg, uric acid > 7 mg/dl and a positive smoking history were considered CVD risk factors. RESULTS: The results showed that with each centimeter increase in WC, the odds of frailty compared with non-frailty was 79% higher, and the odds of frailty compared with pre-frailty was 1.43 times higher in older adults. In addition, the prevalence of pre-frailty compared with non-frailty, pre-frailty, and non-frailty was 10.59 times, 6.08 times, and 73.83 times higher in older individuals > 84 years old, respectively. The results of the present study indicated that the prevalence of pre-frailty compared with non-frailty, frailty compared with pre-frailty, and frailty compared with non-frailty was 2.86 times, 3.01 times, and 14.83 times higher in older adults women, respectively. The comparison between frail and non-frail groups represented that in DM older adults, the prevalence of frailty compared with non-frailty was 1.84 times higher and that of frailty compared with pre-frailty was 98% higher. The older adults with an FBS ≥ 126 mg/dl were 53% more likely to become frail, and with each unit increase in uric acid, the odds of becoming frail increased 2.05 times compared with non-frail older adults, and pre-frail compared with non-frail increased 99%. CONCLUSION: The results demonstrated that CVD risk factors predictive of FS included central obesity, age > 84 years, female sex, DM, FBS ≥ 126, and uric acid > 7. This problem highlights the need for preventive strategies in the older adults who are simultaneously vulnerable to CVD and frailty.

Unusual cause of muscle weakness, type II respiratory failure and pulmonary hypertension: a case report of ryanodine receptor type 1(RYR1)-related myopathy.

BACKGROUND: Patients with congenital myopathies may experience respiratory involvement, resulting in restrictive ventilatory dysfunction and respiratory failure. Pulmonary hypertension (PH) associated with this condition has never been reported in congenital ryanodine receptor type 1(RYR1)-related myopathy. CASE PRESENTATION: A 47-year-old woman was admitted with progressively exacerbated chest tightness and difficulty in neck flexion. She was born prematurely at week 28. Her bilateral lower extremities were edematous and muscle strength was grade IV-. Arterial blood gas analysis revealed hypoventilation syndrome and type II respiratory failure, while lung function test showed restrictive ventilation dysfunction, which were both worse in the supine position. PH was confirmed by right heart catheterization (RHC), without evidence of left heart disease, congenital heart disease, or pulmonary artery obstruction. Polysomnography indicated nocturnal hypoventilation. The ultrasound revealed reduced mobility of bilateral diaphragm. The level of creatine kinase was mildly elevated. Magnetic resonance imaging showed myositis of bilateral thigh muscle. Muscle biopsy of the left biceps brachii suggested muscle malnutrition and congenital muscle disease. Gene testing revealed a missense mutation in the RYR1 gene (exon33 c.C4816T). Finally, she was diagnosed with RYR1-related myopathy and received long-term non-invasive ventilation (NIV) treatment. Her symptoms and cardiopulmonary function have been greatly improved after 10 months. CONCLUSIONS: We report a case of RYR1-related myopathy exhibiting hypoventilation syndrome, type II respiratory failure and PH associated with restrictive ventilator dysfunction. Pulmonologists should keep congenital myopathies in mind in the differential diagnosis of type II respiratory failure, especially in patients with short stature and muscle weakness.

Muscle weakness is more strongly associated with functional outcomes in patients with stroke than sarcopenia or muscle wasting: an observational study.

BACKGROUND: Stroke-related sarcopenia is an important prognosis factor and an intervention target for improving outcomes in patients with stroke. AIM: This study aimed to identify the association between sarcopenia, possible sarcopenia, muscle weakness, muscle mass and calf circumference, and the functional outcomes 3 months after stroke. METHODS: In this single-centre prospective observational study, muscle strength, muscle mass, and calf circumference were measured in patients with acute stroke at hospital discharge. Diagnosis of sarcopenia, possible sarcopenia, muscle weakness, low muscle mass, and low calf circumference were defined according to the 2019 Asian Working Group for Sarcopenia criteria. The primary outcome measure was the modified Rankin Scale (mRS) score at 3 months, with an mRS score of 3 or higher indicating a poor outcome. Logistic regression analysis was conducted to examine independent associations between each assessment and functional outcomes. RESULTS: A total of 247 patients (median age: 73 years) were included in this study. The prevalence of sarcopenia was 28% (n = 70), and in the adjusted model, sarcopenia (aOR = 2.60, 95% CI 1.07-6.31, p = 0.034), muscle weakness (aOR = 3.40, 95% CI 1.36-8.52, p = 0.009), and low muscle mass (aOR = 2.61, 95% CI 1.04-6.52) were significantly associated with poor functional outcome. Nevertheless, other evaluations did not demonstrate an independent association with the outcome. CONCLUSION: Sarcopenia, muscle weakness, and low muscle mass were found to be independently associated with functional outcomes 3 months after stroke, and muscle weakness exhibited the strongest association with outcomes among them.

Adipose tissue is a critical regulator of osteoarthritis.

Osteoarthritis (OA), the leading cause of pain and disability worldwide, disproportionally affects individuals with obesity. The mechanisms by which obesity leads to the onset and progression of OA are unclear due to the complex interactions among the metabolic, biomechanical, and inflammatory factors that accompany increased adiposity. We used a murine preclinical model of lipodystrophy (LD) to examine the direct contribution of adipose tissue to OA. Knee joints of LD mice were protected from spontaneous or posttraumatic OA, on either a chow or high-fat diet, despite similar body weight and the presence of systemic inflammation. These findings indicate that adipose tissue itself plays a critical role in the pathophysiology of OA. Susceptibility to posttraumatic OA was reintroduced into LD mice using implantation of a small adipose tissue depot derived from wild-type animals or mouse embryonic fibroblasts that undergo spontaneous adipogenesis, implicating paracrine signaling from fat, rather than body weight, as a mediator of joint degeneration.

Longitudinal Assessment of Blood-Based Inflammatory, Neuromuscular, and Neurovascular Biomarker Profiles in Intensive Care Unit-Acquired Weakness: A Prospective Single-Center Cohort Study.

BACKGROUND: The diagnosis of intensive care unit (ICU)-acquired weakness (ICUAW) and critical illness neuromyopathy (CINM) is frequently hampered in the clinical routine. We evaluated a novel panel of blood-based inflammatory, neuromuscular, and neurovascular biomarkers as an alternative diagnostic approach for ICUAW and CINM. METHODS: Patients admitted to the ICU with a Sequential Organ Failure Assessment score of ≥ 8 on 3 consecutive days within the first 5 days as well as healthy controls were enrolled. The Medical Research Council Sum Score (MRCSS) was calculated, and motor and sensory electroneurography (ENG) for assessment of peripheral nerve function were performed at days 3 and 10. ICUAW was defined by an MRCSS < 48 and CINM by pathological ENG alterations, both at day 10. Blood samples were taken at days 3, 10, and 17 for quantitative analysis of 18 different biomarkers (white blood cell count, C-reactive protein, procalcitonin, C-terminal agrin filament, fatty-acid-binding protein 3, growth and differentiation factor 15, syndecan 1, troponin I, interferon-γ, tumor necrosis factor-α, interleukin-1α [IL-1α], IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, and monocyte chemoattractant protein 1). Results of the biomarker analysis were categorized according to the ICUAW and CINM status. Clinical outcome was assessed after 3 months. RESULTS: Between October 2016 and December 2018, 38 critically ill patients, grouped into ICUAW (18 with and 20 without) and CINM (18 with and 17 without), as well as ten healthy volunteers were included. Biomarkers were significantly elevated in critically ill patients compared to healthy controls and correlated with disease severity and 3-month outcome parameters. However, none of the biomarkers enabled discrimination of patients with and without neuromuscular impairment, irrespective of applied classification. CONCLUSIONS: Blood-based biomarkers are generally elevated in ICU patients but do not identify patients with ICUAW or CINM. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02706314.

Undetected Neuromuscular Disease in Patients after Heart Transplantation.

(1) Heart transplantation (HTX) improves the overall survival and functional status of end-stage heart failure patients with cardiomyopathies (CMPs). The majority of CMPs have genetic causes, and the overlap between CMPs and inherited myopathies is well documented. However, the long-term outcome in skeletal muscle function and possibility of an undiagnosed underlying genetic cause of both a cardiac and skeletal pathology remain unknown. (2) Thirty-nine patients were assessed using open and standardized interviews on muscle function, a quality-of-life (EuroQol EQ-5D-3L) questionnaire, and a physical examination (Medical Research Council Muscle scale). Whole-exome sequencing was completed in three stages for those with skeletal muscle weakness. (3) Seven patients (17.9%) reported new-onset muscle weakness and motor limitations. Objective muscle weakness in the upper and lower extremities was seen in four patients. In three of them, exome sequencing revealed pathogenic/likely pathogenic variants in the genes encoding nexilin, myosin heavy chain, titin, and SPG7. (4) Our findings support a positive long-term outcome of skeletal muscle function in HTX patients. However, 10% of patients showed clinical signs of myopathy due to a possible genetic cause. The integration of genetic testing and standardized neurological assessment of motor function during the peri-HTX period should be considered.

Ultrasound-guided caudal quadratus lumborum block combined with the greater ischiatic notch plane block as motor-protective analgesia for the pelvic limb in dogs.

OBJECTIVE: To develop an ultrasound-guided caudal quadratus lumborum block (C-QLB) technique in canine cadavers and to compare sensory and motor blockade resulting from the combination of ultrasound-guided greater ischiatic notch (GIN) plane and C-QLB approaches (GIN-CQLB group) versus a lumbosacral plexus (LSP group) approach [combination of lateral pre-iliac (LPI) and parasacral (PS) techniques] in dogs. STUDY DESIGN: Descriptive anatomical study and prospective randomized, blinded, experimental crossover trial. ANIMALS: A total of six canine cadavers and six adult Beagle dogs. METHODS: Phase I: following ultrasound-guided C-QLB injections of 0.3 mL kg-1 of dye, using the interfascial plane located lateral to the quadratus lumborum muscle at the level of the sixth lumbar vertebra (L6) as injection point, the spread of injectate and nerve staining was evaluated using gross anatomical dissection. PHASE II: sensory and motor blockade achieved with the GIN-CQLB or LSP blocks in Beagle dogs were evaluated and compared. The assigned technique was performed with 2% lidocaine: 0.2 mL kg-1 for the GIN and PS approaches and 0.3 mL kg-1 for the C-QLB and LPI approaches. RESULTS: Dissection revealed distribution of dye around the lumbar hypaxial musculature, extending into the paravertebral spaces, with staining of 3 (2-4) [median (interquartile range)] spinal nerves, spanning L3 to L6. The median motor blockade in the GIN-CQLB and LSP groups was 7 (7-8) versus 16 (10-16) (p = 0.026), whereas the median sensory blockade was 5 (4-5) versus 3 (3-3) (p = 0.025), respectively. CONCLUSION AND CLINICAL SIGNIFICANCE: The GIN-CQLB approach desensitized the thigh dermatomes effectively. Compared with the LSP approaches, GIN-CQLB exhibits a motor-protective effect by preserving tonic muscle function.

Changes in Hip and Knee Strength Are Not Associated With Improved Clinical Outcomes After Rehabilitation in Individuals With Patellofemoral Pain: A Critically Appraised Topic.

CLINICAL SCENARIO: Patellofemoral pain (PFP) is a widespread knee disorder encountered in clinical practice. Clinicians have often focused on strengthening hip and knee musculature to improve pain and disability, which are the ultimate clinical goals of PFP treatment. However, PFP literature has shown improvement in pain and disability without concurrent changes in lower-extremity strength after rehabilitation. Although some researchers have achieved a significant increase in strength after rehabilitation in PFP cohorts, there was no association with improved pain and disability. The inconsistent improvements in strength and the lack of association with clinical outcomes call for a critical appraisal of the available evidence to better understand the association between changes in hip and knee strength and improved clinical outcomes in individuals with PFP. CLINICAL QUESTION: Are changes in hip and knee strength associated with improved pain and disability after rehabilitation in individuals with PFP? SUMMARY OF KEY FINDINGS: Four studies met the inclusion criteria and were included in the appraisal. Following rehabilitation, one study achieved strength improvements in knee extension. One study achieved strength improvements in knee extension, but not in hip external rotation and hip abduction. Two studies did not achieve strength improvements in hip external rotation, hip abduction, hip extension, or knee extension. All included studies achieved improvements in pain or disability after rehabilitation. None of the studies found a significant association between changes in hip and knee strength (either improved or not) and improved pain and disability. CLINICAL BOTTOM LINE: There is consistent evidence that changes in hip and knee strength are not associated with improved clinical outcomes after rehabilitation in adults with PFP. STRENGTH OF RECOMMENDATION: Collectively, the body of evidence included is to answer the clinical question aligns with the strength of recommendation of B based on the Strength of Recommendation Taxonomy.

[Research status of lower limb exoskeleton rehabilitation robot].

Lower limb exoskeleton rehabilitation robots are used to improve or restore the walking and movement ability of people with lower limb movement disorders. However, the required functions for patients differ based on various diseases. For example, patients with weak muscle strength require power assistance, patients with spinal cord injuries require motion compensation, patients with gait abnormalities require gait correction, and patients with strokes require neural rehabilitation. To design a more targeted lower limb exoskeleton rehabilitation robot for different diseases, this article summarised and compared existing lower limb exoskeleton rehabilitation robots according to their main functions and the characteristics and rehabilitation needs of various lower limb movement disorders. The correlations between the functions of existing devices and diseases were summarised to provide certain references for the development of new lower limb exoskeleton rehabilitation robots.

[Physical rehabilitation in sarcopenia: modern approaches. (A literature review)]. / Fizicheskaya reabilitatsiya pri sarkopenii: sovremennye podkhody. (Obzor literatury).

The number of middle-aged and elderly population is increasing every year. At the same time, the course of most chronic diseases worsens with age, which can be explained by significant changes in body composition, including redistribution and increase of fat mass and decrease in muscle and skeletal mass. Thus, a decrease in muscle mass becomes intrinsic for the body from the age of 40 and develops on average by 0.5-1.0% per year. The prevalence of patients with sarcopenia is estimated to be between 11 and 50% in different age groups of population: middle, elderly and senile. In addition, the decline in physical activity associated with the urbanization and automation of labor exacerbates the disease at a younger age, which predicts an increase in the number of such patients in the future. OBJECTIVE: To determine the role of physical rehabilitation in sarcopenia. MATERIAL AND METHODS: A systematic review including studies found in PubMed, MedLine, Scopus and Web of Science Core Collections databases for 2019-2022 was conducted. The used enrollment criteria were the following: systematic reviews, including cross-over or cohort studies targeting at persons aged from 40 to 90 years of both sexes, with available data on sarcopenia, its severe form or other combinations of physical performance markers called sarcopenia. The mandatory parameter for inclusion in the study was the presence of the effectiveness assessment of physical rehabilitation without limiting its parameters. The systematic review was performed in accordance with the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020. RESULTS: The best kind of training are 30-60-minute comprehensive methods with predominance of resistance exercises with minimum duration of the course of 3 months and frequency of 3 inconsistent in-person trainings per week under the supervision of a specialist for patients with sarcopenia in order to increase muscle strength and mass, as well as performance. The intensity should consist of the following parameters: start with fewer sets but more repetitions (12-15) with less intensity (55% of maximum) and move to more sets with less repetition (4-6) and greater intensity (>80% of maximum). CONCLUSION: This article describes the parameters of exercises that are most effective in terms of muscle strength and mass increase and safe for patients. The compilation and further study of this complex in practice are needed.

Pompe disease ascertained through The Lantern Project, 2018-2021: Next-generation sequencing and enzymatic testing to overcome obstacles to diagnosis.

The Lantern Project is an ongoing complimentary diagnostic program for patients in the United States sponsored by Sanofi and implemented by PerkinElmer Genomics. It combines specific enzymatic, biomarker, and genetic testing to facilitate rapid, accurate laboratory diagnosis of Pompe disease and several other lysosomal storage diseases, and a multigene next-generation sequencing panel including Pompe disease, LGMD, and other neuromuscular disorders. This article reports data for Pompe disease collected from October 2018 through December 2021, including acid α-glucosidase (GAA) enzyme assay and GAA sequencing (standard or expedited for positive newborn screening [NBS] to rule out infantile-onset Pompe disease [IOPD]) and the Focused Neuromuscular Panel, which includes GAA. One hundred forty patients (12 received only GAA enzyme testing, 128 had GAA sequencing alone or in addition to enzyme assay) have been confirmed with Pompe disease in this project. Eight of the 140 had a variant of unknown significance, but GAA activity ≤2.10 µmol/L/h, thus were confirmed with Pompe disease. Three diagnosed patients 0-2 years old had cross-reactive immunologic material (CRIM)-negative GAA variants and thus IOPD. One additional infant with presumptive IOPD had a homozygous frameshift c.1846del, likely CRIM-negative; symptoms were not provided. Among the 128 patients with molecular results, the c.-32-13T>G splice variant was homozygous in 11, compound-heterozygous in 98, and absent in 19. Proximal muscle weakness (58 patients) was the most common sign reported at testing; elevated creatine kinase (29 patients) was the most common laboratory result. The most common symptom categories were muscular (73 patients), musculoskeletal (13 patients), and respiratory (23 patients). Clinical information was not available for 42 samples, and 17 infants had only "abnormal NBS" or "low GAA" reported. Cardiac symptoms in 7 included potentially age-related conditions in five c.-32-13T>G-compound-heterozygous adults (myocardial infarction, heart murmur/palpitations, congestive heart failure: 1 each; 2 with atrial fibrillation) and hypertrophic cardiomyopathy in 2 children (1 and 2 years old) with presumptive IOPD. One novel GAA variant was observed in a patient with enzyme activity 0.31 µmol/L/h: c.1853_1854ins49, a frameshift pathogenic variant. The Lantern Project demonstrates the combinatorial utility of enzyme assay, targeted single-gene testing, and a focused neuromuscular next-generation sequencing panel in diagnosing Pompe disease.