Changes In Muscle Research Articles

Thigh and paraspinal muscles change after fusionless bipolar fixation for early onset scoliosis in type 2 spinal muscular atrophy: Modifications in the spinal and thigh muscles of subjects with SMA2 and early onset scoliosis

BackgroundSpinal muscular atrophy is a severe, progressive autosomal recessive neuromuscular disorder associated with neuromuscular scoliosis. When bracing is not sufficient to control the deformity, early spinal surgery is required. To the best of our knowledge, no work in the literature have assessed modifications in spinal and thigh muscles of subjects with type 2 spinal muscular atrophy (SMA2) following spinal surgery. ObjectiveThis study aimed to better understand modifications in the spinal and thigh muscles of subjects with SMA2 and early onset scoliosis, before and after minimally invasive fusionless surgery. Methods and settings20 SMA2 patients with confirmed scoliosis on bi-planar low-dose X-ray were included: 10 preoperative and 10 postoperative patients with a minimal follow-up of 5 years after surgery. The surgery consisted of a bilateral sliding rod construct extended from T1 to the sacrum, through a minimally invasive approach. All subjects had fat/water separation muscle magnetic resonance imaging from the spine to the thigh. The percentage of fat degeneration was compared before and after surgery. A quality-of-life survey was performed. ResultsFat infiltration was diffuse and symmetric in both groups of patients, and on average six times more compared to control subjects previously published at thigh level. Adductors, sartorius, and gracilis were less affected with respectively, 51%, 56%, and 57% of fat fraction before surgery. Comparing the preoperative and postoperative groups, fat infiltration was higher in sartorius and multifidus after surgery (p < 0.05). No significant difference was found for the other muscles studied. These results did not affect quality of life. ConclusionThis is the first study to compare fat infiltration of spinal and thigh muscles of SMA2 patients before and after minimally invasive surgery. Our results demonstrate that muscles were globally preserved apart from multifidus and sartorius which were more affected.

Flight power muscles have a coordinated, causal role in hawkmoth pitch turns.

Flying insects solve a daunting control problem of generating a patterned and precise motor program to stay airborne and generate agile maneuvers. In this motor program, each muscle encodes information about movement in precise spike timing down to the millisecond scale. Whereas individual muscles share information about movement, we do not know if they have separable effects on an animal's motion, or if muscles functionally interact such that the effects of any muscle's timing depend heavily on the state of the entire musculature. To answer these questions, we performed spike-resolution electromyography and electrical stimulation in the hawkmoth Manduca sexta during tethered flapping. We specifically explored how flight power muscles contribute to pitch control. Combining correlational study of visually-induced turns with causal manipulation of spike timing, we discovered likely coordination patterns for pitch turns, and investigated if these patterns can drive pitch control. We observed significant timing change of the main downstroke muscles, the dorsolongitudinal muscles (DLMs), associated with pitch turns. Causally inducing this timing change in the DLMs with electrical stimulation produced a consistent, mechanically relevant feature in pitch torque, establishing that power muscles in Manduca have a control role in pitch. Because changes were evoked in only the DLMs, however, these pitch torque features left large unexplained variation. We find this unexplained variation indicates significant functional overlap in pitch control such that precise timing of one power muscle does not produce a precise turn, demonstrating the importance of coordination across the entire motor program for flight.

Beneficial effects of the SGLT2 inhibition on oxidative skeletal muscle in infarcted rats

Abstract Introduction Metabolic, morphological, and biochemical changes in skeletal muscle are common in chronic heart failure patients. Despite the cardioprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition in heart failure, the impact of this drug on skeletal muscle remains poorly understood. This study investigated the effects of SGLT2 inhibitor empagliflozin (EMPA) on the soleus muscle of rats with myocardial infarction (MI)-induced heart failure. Methods One week after MI induction, male Wistar rats were divided into Sham (n=10), Sham+EMPA (n=12), MI (n=10) and MI+EMPA (n=09) groups. EMPA was added to rat chow (5 mg/kg/day) for 12 weeks. Cardiac remodeling was evaluated by echocardiogram. Enzymatic activity and oxidative stress marker concentrations were assessed by spectrophotometry; protein expression was evaluated by Western blotting. After histological analysis of the left ventricle (LV), only rats with MI greater than 35% of total LV area were included in the study. Statistical analysis: ANOVA and Tukey or Kruskal–Wallis and Dunn and t test; p&amp;lt;0.05. Results Infarction size did not differ between groups. Infarcted groups had larger LV systolic and diastolic diameters, LV diastolic area (Sham 47±7.1; Sham+EMPA 48±4.5; MI 100±16.1*; MI+EMPA 85±10.1#† mm2; p&amp;lt;0.05: * vs Sham; # vs Sham+EMPA; † vs MI), and left atrial diameter (Sham 5.62±0.2; Sham+EMPA 5.65±0.3; MI 7.69±1.3*; MI+EMPA 6.85±0.9#† mm; p&amp;lt;0.05: * vs Sham; # vs Sham+EMPA; † vs MI); and lower LV posterior wall shortening velocity and ejection fraction than control groups. Echocardiographic changes were attenuated in MI+EMPA compared to MI. Other results are shown in Picture 1. Conclusion SGLT2 inhibitor empagliflozin attenuates infarction-induced cardiac remodeling in rats. Empagliflozin prevents increase in oxidative stress, modulates protein turnover by IGF-1 pathway, and attenuates morphological and biochemical changes in the soleus muscle of infarcted rats.

Eustachian Tube Dysfunction After LeFort 1 Osteotomy Orthognathic Surgery.

The authors present a 24-year-old male with a history of class III occlusal deformity who underwent a maxillary advancement with LeFort I osteotomies. Eighteen months after surgery, he was diagnosed with bothersome Eustachian tube dysfunction (ETD). Anatomical shifts secondary to the LeFort osteotomies required for maxillary advancement result in vector changes of muscles that regulate the function of the Eustachian tube. This realignment of muscles is suspected to be a major contributing factor in causing this patient's new onset Eustachian tube dysfunction. This article represents a pilot project as data are collected for a retrospective and, ultimately, prospective studies on this topic.

Neosporosis in 21 adult dogs, 2010-2023.

Limited information is available regarding the clinical features, treatment, and prognosis of neosporosis in adult dogs. Describe the clinical signs, laboratory findings, magnetic resonance imaging (MRI) findings, treatment and outcome in adult dogs (>6 months) diagnosed with neosporosis based on consistent clinical signs and positive serology (titer ≥1 : 800) at a referral hospital in Sydney, Australia. Twenty-one client-owned dogs. Retrospective case series of affected dogs between 2010 and 2023. Survival times were determined from onset of clinical signs to date of death or censoring. Clinical signs varied, and were indicative of generalized myopathy (6 dogs), multifocal intracranial disease (7 dogs), myelopathy (4 dogs), polyneuropathy (2 dogs) and single cases of focal myopathy and cerebellar disease. Serum creatine kinase activity was markedly increased (median, 3369 U/L) in most dogs. The most common MRI abnormalities were multifocal intracranial abnormalities (7/13 dogs) and muscle changes (5/13 dogs) whereas T2-weighted cerebellar abnormalities (2/13 dogs) and cerebellar atrophy (1/13) were less common. Treatment response was complete (resolution to normal) in 8 dogs, incomplete (persistent neurological deficits) in 6 dogs, but there was minimal response in 7 dogs. Thirteen dogs (62%) were alive after 6 months and 12 dogs (57%) alive after 1 year. Relapse was common, with 4 dogs experiencing at least 1 relapse event during the follow-up period. Adult-onset neosporosis is uncommon and has variable clinical presentations. Treatment response also is variable, and relapse can occur, even among patients that respond completely to initial treatment.

Photobiomodulation and Physical Exercise Modulate of Cell Survival Proteins in the Skeletal Muscle of Rats with Heart Failure and Diabetes Mellitus.

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p-AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Reversal of Denervation Changes in Infraspinatus Muscle After Operative Management of Paralabral Cysts: An MRI-Based Study

Background: Paralabral cysts at the spinoglenoid notch are rare disorders that can potentially lead to compressive suprascapular neuropathy. Given their infrequency, a standard treatment protocol has not yet been established. Hypothesis/Purpose: This study aimed to assess changes in the infraspinatus muscle using magnetic resonance imaging (MRI) and to compare the outcomes of 2 different surgical methods. It was hypothesized that surgical intervention could alleviate compressive neuropathy, with comparable outcomes between the 2 surgical approaches. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective review encompassed 43 patients undergoing arthroscopic labral repair for a paralabral cyst at the spinoglenoid notch, with cyst decompression (27 patients; labral repair with cyst decompression [LRCD] group) or without cyst decompression (16 patients; labral repair only [LRO] group). Preoperative MRI focused on evaluating the condition of the infraspinatus and teres minor muscles. Electromyography (EMG) was conducted on 36 patients (21 in LRCD and 15 in LRO) to assess suprascapular nerve function. Postoperative evaluations were performed in 35 patients at postoperative 1 year, excluding those lost to follow-up. Postoperative MRI findings (24 patients in LRCD and 11 patients in LRO) and functional outcome scores including recovery of external rotation power were compared with preoperative status in both groups. Results: Preoperative MRI revealed denervation changes or atrophy of the infraspinatus in 26 of the 43 patients (60.4%). Among the 36 patients who underwent preoperative EMG, 21 patients (58.3%; 13 patients in LRCD and 8 patients in LRO) showed evidence of suprascapular neuropathy. A discrepancy between EMG and MRI findings was noted in 10 patients, with 5 patients showing suprascapular neuropathy according to EMG despite normal muscle status on MRI scans, and the remaining 5 vice versa. Notable atrophy of the infraspinatus was seen in 6 patients and teres minor hypertrophy in 5 patients, all of whom exhibited concurrent infraspinatus atrophy. Postoperatively, cyst disappearance was observed in all cases in both LRCD (24 patients) and LRO (11 patients) groups. Denervation changes in the infraspinatus were resolved in all patients. In patients with infraspinatus atrophy, some improvement was noted. Teres minor hypertrophy persisted in 2 of 4 patients. Improvements were similar in both groups (all P > .05). External rotation power improved postoperatively in both groups (from 39.1 ± 18.6 to 50.6 ± 17.7 N in LRCD, P < .001; from 45.1 ± 16.0 to 54.2 ± 10.7 N in LRO, P = .025). Conclusion: Both LRCD and LRO surgical approaches appear to be effective for paralabral cysts at the spinoglenoid notch. Suprascapular neuropathy can be successfully addressed by both methods. However, conditions with severe infraspinatus atrophy and teres minor hypertrophy warrant further investigation in larger series.

Transcriptome analysis identifies potential molecular mechanisms for growth of fast muscle in Chinese perch juvenile

Chinese perch (Siniperca chuatsi) is an important commercial fish species in China. Understanding the molecular mechanisms of growth and development of skeletal muscle is helpful for selection breeding and improving the growth rate of Chinese perch. We analyzed histological and transcriptomic differences in fast muscle of Chinese perch between 30 days post hatching (dph) and 60 dph using histological sections and high-throughput RNA-Seq. The results showed that the diameter of muscle fibers in 30 dph Chinese perch was mainly distributed in range of 30 − 40 μm, and that of 60 dph was primarily in the range of 40 − 50 μm. 34 differentially expressed genes (DEGs) were identified in the fast muscle of Chinese perch between 30 and 60 dph, of which 9 were up-regulated and 25 were down-regulated (60 dph vs 30 dph). The DEGs, including MYH4, ENO3, Bag3, krt13 and krt18, are associated with muscle cell differentiation and fusion in Chinese perch. The analysis of the protein–protein interaction network of DEGs revealed that FOS, junb and EGR1 may involve in the development of fast muscle. KEGG enrichment results showed that the up-regulated genes in the 60 dph were associated with several pathways related to metabolism and protein synthesis, such as glycosphingolipid biosynthesis and aminoacyl-tRNA biosynthesis. The results suggest that the development of fast muscle in Chinese perch from 30 to 60 dph is accompanied by an increase in muscle fiber diameter and changes in gene expression related to muscle cell differentiation and protein synthesis.Abbreviations: DEGs, differentially expressed genes; dph, days post hatching; FC, fold change; FDR, False Discovery Rate; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; MyHCs, Myosin heavy chains; qRT-PCR, quantitative real-time PCR.

Single-nucleus transcriptomics reveals subsets of degenerative myonuclei after rotator cuff tear-induced muscle atrophy.

Rotator cuff tear (RCT) is the primary cause of shoulder pain and disability and frequently trigger muscle degeneration characterised by muscle atrophy, fatty infiltration and fibrosis. Single-nucleus RNA sequencing (snRNA-seq) was used to reveal the transcriptional changes in the supraspinatus muscle after RCT. Supraspinatus muscles were obtained from patients with habitual shoulder dislocation (n = 3) and RCT (n = 3). In response to the RCT, trajectory analysis showed progression from normal myonuclei to ANKRD1+ myonuclei, which captured atrophy-and fatty infiltration-related regulons (KLF5, KLF10, FOSL1 and BHLHE40). Transcriptomic alterations in fibro/adipogenic progenitors (FAPs) and muscle satellite cells (MuSCs) have also been studied. By predicting cell-cell interactions, we observed communication alterations between myofibers and muscle-resident cells following RCT. Our findings reveal the plasticity of muscle cells in response to RCT and offer valuable insights into the molecular mechanisms and potential therapeutic targets of RCT.

Ultrasound visualization of Botulinum toxin injection: Identifying clinical correlates to optimize outcomes in spasticity management.

Botulinum toxin injections are well established and commonly used for spasticity management. Clinicians strive to optimize outcomes from toxin injections. One potential complication is toxin spread beyond the intended muscle, which can lead to unwanted weakness. The utilization of ultrasound allows direct visualization of target muscles and identification of toxin leakage from the target muscle. Ultrasound evaluation of clinical factors that correlate to toxin leakage have not been studied. To identify cases of botulinum toxin injectate leak beyond the targeted muscle during ultrasound-guided spasticity injections and associate cases of leak with predictive clinical factors, which include muscle size, fibroadipose changes, and number of previous injections. This was a prospective observational study. An outpatient clinic in an academic medical center. Patients who demonstrated wrist flexor spasticity warranting intervention were invited to participate. Patients received standard-of-care spasticity management with injection of onabotulinumtoxinA into the flexor carpi radialis muscle based upon clinical presentation and prescribing guidelines. Ultrasound video was recorded, and a blinded review was conducted by the study team. The primary outcome measure was visualized leak of injectate on recorded ultrasound video. Documented leak was then associated with clinical factors including diameter of the flexor carpi radialis, volume of injectate used, history of prior injections, and fibrotic change of the muscle. The study included 54 patients, 77.8% of whom had an underlying diagnosis of cerebrovascular accident. Injectate leak was observed in 18.5% of injections and could not be confirmed in 9.3% of injections. Multivariable analysis demonstrated increased odds of leak with higher Modified Heckmatt Scale score. No statistically significant increase in leak was noted with higher volume of injectate or smaller muscle diameter. Extramuscular leak of botulinum toxin injection may be associated with fibroadipose muscle change.

L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway

IntroductionL-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism. MethodsSOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses. ResultsIt was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries.The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway. ConclusionIn summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.

Effects of altered contractile environment on muscle shape change in the triceps surae.

Skeletal muscles change shape when they contract. Current insights into the effects of shape change on muscle function have primarily come from experiments on isolated muscles operating at maximal activation levels. However, when muscles contract and change shape, the forces they apply onto surrounding muscles will also change. The impact of an altered contractile environment (i.e., mechanical behaviour of surrounding muscle) on muscle shape change, remains unknown. To address this, we altered the mechanical contributions of the gastrocnemii during isometric plantarflexion contractions [via changing knee angle] and determined if there were associated changes in how the muscles of the triceps surae bulged in thickness during a ramped contraction. We combined B-mode ultrasound imaging with surface electromyography to quantify the neuromechanical contributions of the medial (MG) and lateral gastrocnemius (MG) and soleus (SOL) muscles during isometric plantarflexion contractions. Our results demonstrated that at the same SOL activity levels, altering knee angle had no influence on the magnitude of muscle shape change (thickness) in the triceps surae muscles. We observed high levels of inter-individual variability in muscle bulging patterns, particularly in the knee flexed position, suggesting a complex relationship between muscle bulging and activation strategies in the triceps surae, which may be related to differences in muscle mechanical properties between participants or across muscles. Our findings highlight the dynamics of in vivo bulging interactions among muscles within the triceps surae and provide insights for future investigations into the impact of altered contractile environments on three-dimensional muscle deformations and force production.

Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension.

Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis. Moreover, there is ectopic complement deposition and inflammatory macrophage accumulation in the pulmonary vasculature. However, the effects of ferroptosis inhibition on these pathogenic mechanisms and the cellular landscape of the pulmonary vasculature are incompletely defined. Multiomics and physiological analyses evaluated how ferroptosis inhibition-modulated preclinical PAH. The impact of adeno-associated virus 1-mediated expression of the proferroptotic protein ACSL (acyl-CoA synthetase long-chain family member) 4 on PAH was determined, and a genetic association study in humans further probed the relationship between ferroptosis and pulmonary hypertension. Ferrostatin-1, a small-molecule ferroptosis inhibitor, mitigated PAH severity in monocrotaline rats. RNA-sequencing and proteomics analyses demonstrated ferroptosis was associated with PAH severity. RNA-sequencing, proteomics, and confocal microscopy revealed complement activation and proinflammatory cytokines/chemokines were suppressed by ferrostatin-1. In addition, ferrostatin-1 combatted changes in endothelial, smooth muscle, and interstitial macrophage abundance and gene activation patterns as revealed by deconvolution RNA-sequencing. Ferroptotic pulmonary arterial endothelial cell damage-associated molecular patterns restructured the transcriptomic signature and mitochondrial morphology, promoted the proliferation of pulmonary artery smooth muscle cells, and created a proinflammatory phenotype in monocytes in vitro. Adeno-associated virus 1-Acsl4 induced an inflammatory PAH phenotype in rats. Finally, single-nucleotide polymorphisms in 6 ferroptosis genes identified a potential link between ferroptosis and pulmonary hypertension severity in the Vanderbilt BioVU repository. Ferroptosis promotes PAH through metabolic and inflammatory mechanisms in the pulmonary vasculature.

Quantifying the Fascicular Changes in Recovered Achilles Tendon Patients Using Diffusion Magnetic Resonance Imaging and Tractography.

Regardless of the way of treatment, persistent deficits in calf muscles in recovered patients from Achilles tendon rupture (ATR) exist long-term postinjury. Studies on calf muscle changes mostly highlight morphological changes in the calf muscles and Achilles tendon. However, limited attention has been given to fascicular changes. Diffusion tensor imaging (DTI) can provide a better understanding of the characteristics and properties of tissues with organized microstructure. In the current study, we used DTI-derived indices (mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues-λ 1, λ 2, and λ 3) and fiber tractography to better understand the soleus muscle after recovery from ATR by comparing the results of injured legs with healthy ones. Our findings suggest that the standard deviations of measured parameters (FA, MD, and eigenvalues) within the soleus muscle are better predictors of the changes associated with the ATR as compared to the control counterpart for the volumetric region of interest (ROI). Additionally, in four out of five participants, smaller tracts were observed in the injured leg compared to the healthy one, as evidenced by the fiber length distribution of the tracts. Altogether, this study demonstrates the feasibility of the DTI and fiber tractography approaches to quantify the fascicular changes in the individuals recovered from ATR.

Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.

Neck muscle stiffness during craniocervical flexion under functional upper extremity conditions in patients with chronic non-specific neck pain: A shear-wave elastography study

ObjectiveThe primary objective of the present study was to examine the differences and patterns of change in the neck extensor (NE) muscle stiffness during the Cranio-cervical flexion (CCF) task under different functional conditions of the upper extremity between CNSNP participants and asymptomatic controls. MethodsIn the current case-control study, 25 participants with CNSNP and 25 asymptomatic controls were recruited. The stiffness of the superficial (i.e., upper trapezius, splenius capitis, and semispinalis capitis) and deep (i.e., semispinalis cervicis and multifidus) NE muscles was measured at prone resting, sitting resting, and during the CCF task in different functional conditions of upper extremity using shear wave elastography. ResultsThe findings showed that there was a significant main effect of condition in all NE muscles (P < 0.05), as well as a significant main effect of the group on the stiffness of superficial neck muscles (P < 0.05), indicating higher muscle stiffness in participants with CNSNP compared to the control group. There was no significant group-by-condition interaction effect on the stiffness of NE muscles (P > 0.05), except for the upper trapezius muscle (P = 0.00), indicating a different pattern of stiffness changes compared to the other muscles. ConclusionsIndividuals with CNSNP exhibited significantly greater stiffness in the superficial neck extensor muscles compared to healthy controls. Furthermore, the CCF task performed under functional upper extremity conditions, which includes bilateral shoulder scaption and shoulder abduction-external rotation while seated, resulted in increased stiffness of the NE muscles. Additionally, participants with CNSNP exhibited a higher magnitude of stiffness changes in the upper trapezius muscle across different conditions.

CAUSES OF PAIN IN THE MUSCLES OF THE LOWER EXTREMITIES IN CHILDREN WITH CEREBRAL PALSY

A high level of muscle spasticity in children with cerebral palsy is one of the causes of degenerative and dystrophic changes in tissues. Against the background of high spasticity, there is a violation of blood flow in the vessels of the lower extremities, which leads to changes in subfascial pressure and the formation of primary pain syndromes. The analysis of the literature shows the need to study the issues related to the mechanism of formation of changes in the muscles and determine the primary causes of pain. Objective. Тo study the mechanism of changes in the muscles of the lower extremities, as well as the primary causes of pain syndrome. Methods. The analysed indicators were obtained during the treatment of 40 patients with cerebral palsy, who were divided into 3 groups depending on the muscle tone disorder. Clinical and instrumental methods were used to examine patients. The data obtained were statistically processed with the determination of M ± m, the coefficient of reliability according to Student’s criteria. Results. According to the results of the study, high spasticity leads to impaired blood flow and increased subfascial pressure in the musculofascial sheaths. There is an inverse correlation between the increase in subfascial pressure, the diameter of the vessel lumen and blood flow velocity. This is one of the causes of degenerative and denervation changes in muscles and fascia. It was proved that the occurrence of primary pain in the lower extremities is caused by various etiological causes: tissue ischemia; increased subfascial pressure; narrowing of pathologically significant anatomical areas in which nerves lie; degenerative and dystrophic changes in the joints. Conclusions. The study found that the cause of changes in the muscles and fascia is a violation of blood flow, a change in subfascial pressure in the musculofascial cases of the lower extremities. The occurrence of pain in the lower extremities in children with cerebral palsy is multifactorial in nature and consists of myofascial, articular, and tunnel syndromes.

DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy

Mitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy, but how muscle senses and adapts to mitochondrial dysfunction is not well understood. Here, we used diverse mouse models of mitochondrial myopathy to show that the signal for mitochondrial dysfunction originates within mitochondria. The mitochondrial proteins OMA1 and DELE1 sensed disruption of the inner mitochondrial membrane and, in response, activated the mitochondrial integrated stress response (mt-ISR) to increase the building blocks for protein synthesis. In the absence of the mt-ISR, protein synthesis in muscle was dysregulated causing protein misfolding, and mice with early-onset mitochondrial myopathy failed to grow and survive. The mt-ISR was similar following disruptions in mtDNA maintenance (Tfam knockout) and mitochondrial protein misfolding (CHCHD10 G58R and S59L knockin) but heterogenous among mitochondria-rich tissues, with broad gene expression changes observed in heart and skeletal muscle and limited changes observed in liver and brown adipose tissue. Taken together, our findings identify that the DELE1 mt-ISR mediates a similar response to diverse forms of mitochondrial stress and is critical for maintaining growth and survival in early-onset mitochondrial myopathy.

8068 Beneficial Effects of a Personalized Exercise Program for Patients with Cushing's Disease and Acromegaly After Biochemical Control

Abstract Disclosure: E. Valassi: None. L. Martel-Duguech: None. H. Bascuñana: None. V. Priego-Corredor: None. J. Viñals-Ribé: None. O. González-Viñuela: None. T. Caparrós-Pons: None. S.M. Webb: None. Background: Patients with Cushing’s disease (CD) in remission and controlled acromegaly (ACRO) present with residual metabolic derangements, muscle dysfunction, and poor quality of life (QoL). Although exercise is known to exert positive effects on psychophysical health in several conditions, evidence demonstrating its potential benefits in pituitary diseases is scanty. Main hypothesis: A personalized program of combined (aerobic and resistance training) exercise lasting 12 weeks improves cardiometabolic parameters, body composition, physical performance and QoL in patients with CD in remission and controlled ACRO. Methodology: Ten female patients with CD in remission [mean (±SD) age, 59±4 years, mean (±SD) BMI, 35±2 Kg/m2, median (IQR) duration of remission, 5(4) years] and 10 male patients with controlled ACRO [mean (±SD) age, 53±9 years, mean (±SD) BMI, 27±4 Kg/m2, median (IQR) duration of control, 6(3) years] underwent a 12-week, structured, personalized program of combined aerobic and resistance exercise, under the supervision of professional trainers. We evaluated the following parameters at baseline and within 72 hours after the completion of the exercise program: blood pressure (BP), BMI, waist and neck circumferences; physical performance (gait speed, hand grip strength, 30-Second Chair Stand; Timed “Up and Go”); lumbar and femoral bone mineral density (BMD) and body composition, using dual x-ray absorptiometry (DXA); muscle thickness (cm) at the middle and distal third of rectus femoris (RF) and vastus intermedius (VI) on both sides, using muscle ultrasound scans in the transverse plane (Philips Affiniti 70; The Netherlands); quality of life (QoL), using the questionnaires CushingQoL in CD patients and AcroQoL in ACRO patients. Major results: After completion of the exercise program, CD patients had lower diastolic BP and waist circumference as compared with baseline (p&amp;lt;0.05). Physical performance globally improved (p&amp;lt;0.01 for all function tests). Femoral BMD was higher, percentage of lean mass increased while trunk fat decreased (p&amp;lt;0.01). RF and VI muscle thickness was greater at both the middle and distal third on the right side (p&amp;lt;0.01), and at the distal third on the left as compared with baseline (p&amp;lt;0.05). ACRO patients had a lower systolic BP as compared with baseline. Gait speed and hand grip strength increased while performance on the 30-Second Chair Stand improved (p&amp;lt;0.05). Muscle thickness at the middle third of the right RF was greater as compared with baseline (p&amp;lt;0.05). QoL was unchanged in both CS and ACRO patients at the end of the program. Conclusions: A customized exercise program promotes beneficial cardiometabolic and muscle changes in patients with CD and ACRO and, therefore, should be offered in a specialized pituitary clinic, within an integrated multidisciplinary team approach. Study financed by ISCIII research project number FIS PI21/01223 Presentation: 6/1/2024

Role of Ultrasound in the Evaluation of Skeletal Muscle Changes in Patients with Type 2 Diabetes Mellitus

Abstract Background Diabetes is a global public health problem, with type 2 diabetes mellitus (T2DM) accounting for more than 90% of the diabetic population and it has been consistently reported as one of the strongest correlates of mobility limitation, especially in older people, and a potential risk factor for future mobility disability and loss of independence. Long-term complications and diabetes-related comorbidities only partially explain the excess risk of disability associated with diabetes. Changes in body composition, in particular progressive loss of muscle mass and increase in fat mass, with decline in muscle strength and quality have been proposed as additional potential mediators of the association between diabetes and disability. Aim of the Work to investigate the differences in Skeletal muscle ultrasound features in people with and without type 2 diabetes mellitus. Patients and Methods This was a Case control study conducted at the Ultrasound Radiology Unit, Radiology Department, Ain Shams University Hospitals from July, 2023 to January 2024. The study was performed on simple random sample consists of 36 T2DM patients on regular follow up in the endocrinology clinics in Ain Shams University Hospitals. And 36 Healthy controls came for routine checkup in Ain Shams University Hospitals clinics and meeting the study inclusion criteria. A signed informed consent was obtained from all patients and controls prior to inclusion in the study after explaining the procedure details. The approval of research ethical committee of faculty of Medicine - Ain Shams University was obtained before starting the study. The privacy of participants and confidentiality of data was guaranteed during the various phases of the study. Results we measured three ultrasonic parameters. MT, FL and PA. The FL and PA are measured in both relaxed and contracted states. the DPN group had the lowest MT, FL at both rest and contracted states and PA at contracted state as well as the lowest ΔFL and ΔPA. The control group had the highest MT, FL at both rest and contracted states and PA at contracted state as well as the highest ΔFL and ΔPA. The non-DPN group had intermediate values for the same variables. The differences among the groups were statistically significant for all the variables except for the pennation angle at rest. It showed that the ΔFL of the DPN group was significantly lower than that of the non-DPN group (p &amp;lt; 0.001), which was similar to a previous conclusion that the gastrocnemius fascicles undergo the smallest length changes in a DPN group. Conclusion The combination of MT,ΔFL and ΔPA of the MG showed high-diagnostic accuracy (sensitivity &amp;gt;80%; specificity &amp;gt;95%) for predicting DPN, which could be used for rapid screening in the future. Early muscle ultrasound screening should be timely carried out in patients with T2DM, especially those with a long disease course and poor long-term blood glucose levels, and there is no difference between men and women.