Muscle Deficits Research Articles

Correlating postoperative muscle and long-term functional outcomes with intraoperative muscle motor evoked potential changes in patients with benign intramedullary spinal cord tumors

BackgroundWe aimed to determine the diagnostic accuracy of intraoperative muscle motor evoked potentials (mMEPs) in predicting postoperative motor deficits in individual muscles of patients with benign intramedullary spinal cord tumors (IMSCTs), and to correlate them with long-term functional outcome.MethodsA retrospective study of patients operated for benign IMSCTs from 2009 to 2021 was performed. Sixty-nine patients in whom baseline mMEP recordings were obtained from at least one muscle were included for analysis. A persistent drop of the baseline mMEP by ≥ 50% from baseline was considered significant.ResultsThe mean age of the patients was 33.2 ± 15.8 years and 47 (68.1%) of them were male. The most common tumor was ependymoma (56.5%). Baseline mMEPs were obtained in 400/1011 muscles that were monitored. Postoperative worsening of motor power was noted in 109/400 (27.3%) muscles with baseline mMEP recordings compared to 213/611 (34.9%) muscles with no baseline recordings (p = 0.01). Patients who had deterioration of mMEPs had a significantly higher rate of worsening of muscle power postoperatively compared to those who had no deterioration of mMEPs (100% vs. 30.2%, p < 0.001). The sensitivity of mMEPs in predicting postoperative motor function in monitored muscles was 53.1% (95% CI 43.5–62.6), specificity was 97.9% (95% CI 95.5–99.2), PPV was 90.9% (95% CI 81.6–95.7) and NPV was 84.1% (95% CI 81.3–86.6). At median follow-up of 18.5 (IQR 13–40) months, there was no significant difference in Nurick grade between patients who had intraoperative deterioration of mMEPs and those who did not.ConclusionsIntraoperative mMEP reduction had high specificity and low sensitivity for predicting immediate postoperative neurological deficits following IMSCT resection. However, the majority of patients who had worsening of mMEPs, recovered to their preoperative functional status or a better status at follow-up and there was no significant difference in long-term functional outcome between patients with and without intraoperative mMEP changes.

Quantifying Muscle Volume Deficits Among 38 Lower Extremity Muscles in Collegiate Football Athletes After Anterior Cruciate Ligament Reconstruction.

Quadriceps dysfunction is ubiquitous after anterior cruciate ligament (ACL) reconstruction (ACLR). Addressing quadriceps dysfunction is crucial to improve function, reduce the reinjury risk, and maintain long-term knee health. While deficits specific to the quadriceps are well documented, less is known about the effect of an ACL injury on other lower extremity muscle groups. The purpose of this exploratory analysis was to quantify and rank lower extremity muscle volume deficits using magnetic resonance imaging in collegiate football athletes after ACLR. It was hypothesized that the quadriceps muscles would present with the greatest deficits and that compensatory hypertrophy of muscles at adjacent joints such as the hip and ankle would be observed. Cross-sectional study; Level of evidence, 3. This study is a secondary analysis from an ongoing multicenter prospective cohort study involving Division I collegiate football athletes. Athletes who underwent primary unilateral ACLR (1 [3%] allograft, 2 [7%] quadriceps tendon autograft, 22 [73%] bone-patellar tendon-bone autograft, 5 [17%] hamstring tendon autograft) and magnetic resonance imaging were included. Muscle volumes (mL·kg-1·m-1) were quantified bilaterally from 38 lower extremity muscles using machine learning technology. Paired-samples t tests were performed between limbs for each muscle, which were then ranked and visualized in a forest plot based on standardized mean differences (surgical - nonsurgical limb). A total of 30 athletes (mean time from surgery, 27.9 ± 19.0 months) were included. The largest muscle volume deficits in the surgical limb were seen in the 3 uniarticular quadriceps muscles, followed by the biarticular triceps surae muscles. The rectus femoris and soleus did not show significant differences between limbs. Conversely, the fibularis muscle group had a greater muscle volume in the surgical limb compared with the nonsurgical limb. Most other muscle groups did not present significant differences between limbs. Persistent quadriceps atrophy in a cohort of high-level athletes over 2 years after ACLR was highlighted in this study. Deficits in the gastrocnemius muscles, but not in the soleus, were also identified. This comprehensive approach examining various lower extremity muscles revealed latent muscle volume deficits present after ACLR.

Nutritional Interventions to Attenuate Quadriceps Muscle Deficits following Anterior Cruciate Ligament Injury and Reconstruction.

Following anterior cruciate ligament (ACL) injury, quadriceps muscle atrophy persists despite rehabilitation, leading to loss of lower limb strength, osteoarthritis, poor knee joint health and reduced quality of life. However, the molecular mechanisms responsible for these deficits in hypertrophic adaptations within the quadriceps muscle following ACL injury and reconstruction are poorly understood. While resistance exercise training stimulates skeletal muscle hypertrophy, attenuation of these hypertrophic pathways can hinder rehabilitation following ACL injury and reconstruction, and ultimately lead to skeletal muscle atrophy that persists beyond ACL reconstruction, similar to disuse atrophy. Numerous studies have documented beneficial roles of nutritional support, including nutritional supplementation, in maintaining and/or increasing muscle mass. There are three main mechanisms by which nutritional supplementation may attenuate muscle atrophy and promote hypertrophy: (1) by directly affecting muscle protein synthetic machinery; (2) indirectly increasing an individual's ability to work harder; and/or (3) directly affecting satellite cell proliferation and differentiation. We propose that nutritional support may enhance rehabilitative responses to exercise training and positively impact molecular machinery underlying muscle hypertrophy. As one of the fastest growing knee injuries worldwide, a better understanding of the potential mechanisms involved in quadriceps muscle deficits following ACL injury and reconstruction, and potential benefits of nutritional support, are required to help restore quadriceps muscle mass and/or strength. This review discusses our current understanding of the molecular mechanisms involved in muscle hypertrophy and disuse atrophy, and how nutritional supplements may leverage these pathways to maximise recovery from ACL injury and reconstruction.

Regenerative failure of sympathetic axons contributes to deficits in functional recovery after nerve injury.

Renewed scientific interest in sympathetic modulation of muscle and neuromuscular junctions has spurred a flurry of new discoveries with major implications for motor diseases. However, the role sympathetic axons play in the persistent dysfunction that occurs after nerve injuries remains to be explored. Peripheral nerve injuries are common and lead to motor, sensory, and autonomic deficits that result in lifelong disabilities. Given the importance of sympathetic signaling in muscle metabolic health and maintaining bodily homeostasis, it is imperative to understand the regenerative capacity of sympathetic axons after injury. Therefore, we tested sympathetic axon regeneration and functional reinnervation of skin and muscle, both acute and long-term, using a battery of anatomical, pharmacological, chemogenetic, cell culture, analytical chemistry, and electrophysiological techniques. We employed several established growth-enhancing interventions, including electrical stimulation and conditioning lesion, as well as an innovative tool called bioluminescent optogenetics. Our results indicate that sympathetic regeneration is not enhanced by any of these treatments and may even be detrimental to sympathetic regeneration. Despite the complete return of motor reinnervation after sciatic nerve injury, gastrocnemius muscle atrophy and deficits in muscle cellular energy charge, as measured by relative ATP, ADP, and AMP concentrations, persisted long after injury, even with electrical stimulation. We suggest that these long-term deficits in muscle energy charge and atrophy are related to the deficiency in sympathetic axon regeneration. New studies are needed to better understand the mechanisms underlying sympathetic regeneration to develop therapeutics that can enhance the regeneration of all axon types.

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.

7140 Assessing Bone Mineral Density and Cortical Geometry Using High-resolution Peripheral Quantitative Computed Tomography and Dual Energy X-ray Absorptiometry in Pediatric Survivors of High-risk Neuroblastoma with Growth Failure

Abstract Disclosure: S. Gera: None. M. Guo: None. N. Pollock: None. I. Hampton: None. M. Song: None. D. Weber: None. M. Denburg: None. S. Mostoufi-Moab: None. Introduction: Survival of children with high-risk neuroblastoma (HR-NBL) has increased with multimodal therapy. Cis-retinoic acid (cis-RA), cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure, posing a threat to skeletal structure. HR-NBL survivors demonstrate profound growth failure. DXA measures areal bone mineral density (aBMD). DXA is confounded by short stature and fails to distinguish between trabecular and cortical bone. We previously reported no significant difference in height-per-age adjusted aBMD-Z in HR-NBL survivors compared to healthy controls[1]. However, aBMD-Z in severe short stature may attenuate bone density deficits. High-resolution peripheral quantitative computed tomography (HRpQCT) yields 3D measures of volumetric BMD and bone architecture. Objectives: Assess volumetric BMD (vBMD) and cortical structure using distal tibia HRpQCT and leg lean mass by DXA in HR-NBL survivors compared to healthy controls in a cross-sectional study. Methods: We prospectively enrolled 20 HR-NBL survivors (median age 12.2 yrs, range 9.5 to 15.8, 7 female) treated with cis-RA (median age 2.6 yrs at start of therapy, range 0.3-9.1), and 20 age-, sex-, and race-matched healthy controls. We assessed leg lean mass adjusted for leg length by DXA. For HRpQCT, we compared tibia length (cm), cortical and trabecular vBMD (mg HA/cm3), geometry parameters (cortical and trabecular area [mm2]), and structural parameters (cortical thickness [μm] and porosity, trabecular number [mm-[1]] and separation [μm]). Outcomes were compared using Student’s t-test or Mann-Whitney U test. Linear regression models assessed difference in outcomes of bone microarchitecture and leg lean mass between both groups. Results: Compared to controls, tibia length was significantly shorter in HR-NBL survivors (32.3 ± 0.8 vs. 35.7 ± 0.6, P&amp;lt;0.005). HR-NBL survivors demonstrated lower cortical area (187.6 ± 43.8 vs. 218.7 ± 42.3, P&amp;lt;0.05), cortical perimeter (62.4 ± 7.71 vs. 69.5 ± 8.1, P&amp;lt;0.01), and leg lean mass Z-score (-1.47 ± 1.34 vs. -0.20 ± 0.84, P&amp;lt;0.001) compared to controls. Cortical geometry deficits were explained by muscle deficits (P&amp;lt;0.001). Trabecular area, BMC, areal and volumetric BMD, and measures of bone structure were not significantly different in HR-NBL survivors compared to controls. IGF-1 and 25-OH D levels had no significant effects on DXA or HRpQCT parameters. Conclusion: Bone density is not severely impacted in HR-NBL survivors. Muscle deficits persist years after treatment and explain cortical geometry deficits. HRpQCT substantiates prior DXA evaluation in HR-NBL survivors with significant short stature, demonstrating preserved bone density and structure. 1.Guo et al. Sarcopenia and preserved bone mineral density in pediatric survivors of high-risk neuroblastoma with growth failure. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):1024-1033. Presentation: 6/3/2024

The Use of Whole-Body Vibration, Electrical Stimulation, and Magnetic Stimulation in Muscle Dystrophy Patients: A Scoping Review.

The purpose of this scoping review was to report the effects of vibration therapy, electrical stimulation, and transcranial magnetic stimulation on patients with muscle dystrophies. The outcome measures were muscle strength, body composition, balance, and functional mobility of these patients.We used the PreferredReportingItemsfor Systematic reviews andMeta-Analyses (PRISMA) guidelines and the Arksey and O'Malley framework. The literature review was conducted on PubMed. We included studies that were written in English, were peer-reviewed, without regard to the publication date, and implemented a form of "vibration therapy" or "electrical stimulation" or "magnetic stimulation" as an intervention program of any duration. Overall, 14 studies were retrieved. Most of the studies applied whole-body vibration (WBV) therapy or electrical stimulation and only one was found that implemented transcranial magnetic stimulation. The interventions were reported but there was a variety in duration or the frequency of the program, as well as in the disease progression of the patients.It seems that WBV, electrical stimulation, and magnetic stimulation have positive outcomes, but these vary depending on the muscle deficits and limitations of the patients with muscle dystrophy. It is recommended that future studies should be conducted in order to determine the ideal prescription of each intervention, so as to be as beneficial as possible.

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability. A mouse model with inducible deletion of the p53-encoding gene, Trp53, in skeletal muscle was generated using the Cre-loxP-system. A detailed analysis of nutrient metabolism in mice with control and knockout genotypes was performed under ad libitum fed and fasting conditions and in exercised mice. Acute deletion of p53 in myofibres of mice activated catabolic nutrient usage pathways even under ad libitum fed conditions, resulting in significantly increased overall energy expenditure (+10.6%; P=0.0385) and a severe nutrient deficit in muscle characterized by depleted intramuscular glucose and glycogen levels (-62,0%; P<0.0001 and -52.7%; P<0.0001, respectively). This was accompanied by changes in marker gene expression patterns of circadian rhythmicity and hyperactivity (+57.4%; P=0.0068). These metabolic changes occurred acutely, within 2-3days after deletion of Trp53 was initiated, suggesting a rapid adaptive response to loss of p53, which resulted in a transient increase in lactate release to the circulation (+46.6%; P=0.0115) from non-exercised muscle as a result of elevated carbohydrate mobilization. Conversely, an impairment of proteostasis and amino acid metabolism was observed in knockout mice during fasting. During endurance exercise testing, mice with acute, muscle-specific Trp53 inactivation displayed an early exhaustion phenotype with a premature shift in fuel usage and reductions in multiple performance parameters, including a significantly reduced running time and distance (-13.8%; P=0.049 and -22.2%; P=0.0384, respectively). These findings suggest that efficient nutrient conservation is a key element of normal metabolic homeostasis that is sustained by p53. The homeostatic state in metabolic tissues is actively maintained to coordinate efficient energy conservation and metabolic flexibility towards nutrient stress. The acute deletion of Trp53 unlocks mechanisms that suppress the activity of nutrient catabolic pathways, causing substantial loss of intramuscular energy stores, which contributes to a fasting-like state in muscle tissue. Altogether, these findings uncover a novel function of p53 in the short-term regulation of nutrient metabolism in skeletal muscle and show that p53 serves to maintain metabolic homeostasis and efficient energy conservation.

Green synthesis of silver nanoparticles using food supplement from Avena sativa L., and their antioxidant, antiglycation, and anti-aging activities: In vitro and in silico studies

Food supplement of Avena sativa L. dry extract (AsDE) is produced with green leaves of wild oats and it is commonly used in patients with cognitive disorders and muscle deficits. These symptoms and pathologies can be promoted and/or aggravated by oxidative stress and protein glycation. In order to prevent or treat these disorders, new formulations that could enhance and benefit AsDE have been developed and the formation of metallic nanoparticles by green synthesis has shown to be an alternative. Thus, this study aimed to prepare silver nanoparticles (AgNPs) by green synthesis using AsDE and characterize these AgNPs. Besides, it aimed to evaluate in vitro antioxidant and antiglycation activities of AsDE and AgNPS, and analyze in vitro and in silico inhibitory action on aging enzymes (collagenase, elastase, and tyrosinase). UV–visible spectroscopy, Zeta potential and scanning transmission electron microscopy were used to characterize AgNPs. Antioxidant activity was determined by DPPH free radical scavenging, ferric ion reducing power (FRAP), lipid peroxidation inhibition, ABTS radical scavenging, and oxygen radical absorption capacity (ORAC). Molecular docking analyses were performed to evaluate interactions between the major compounds of AsDE and aging enzymes or DNA. Antioxidant tests demonstrated antioxidant activity of 19.67 % for AsDE and 42.98 % for AgNPs in DPPH test; and 115.67 µM Trolox Equivalent (TE)/g for AsDE and 554.33 µM TE/g for AgNPs in FRAP test. In addition, AsDE and AgNPs inhibited 25.40 % and 11.33 % of lipid peroxidation, respectively, and presented 255.22 µM TE/g for AsDE and 317.44 µM TE/g for AgNPs in ABTS test. AsDE and AgNPs exhibited antioxidant potential observed in ORAC assay. In addition, AsDE presented inhibitory action on collagenase, elastase and tyrosinase activities (78.23 %, 68.14 % and 62.27 % inhibition, respectively). Antiglycation tests demonstrated that bovine serum albumin exposed to ribose and treated with AsDE at 0.5 mg/mL exhibited the highest percentage of free amino groups (45.21 %), while samples treated with AgNPs showed 35.41 % free amino groups. On the other hand, AgNPs exhibited the highest percentage of inhibition of advanced glycation end-products formation (85.75 %), which did not differ from aminoguanidine, a known antiglycation agent. Besides, relative electrophoretic mobility assay demonstrated that samples treated with AsDE at 0.1 mg/mL or AgNPs showed antiglycation activity comparable to aminoguanidine. The in silico assays showed interactions between the major compounds of AsDE and aging enzymes or DNA. Therefore, results represent an important indicator for the development and discovery of new nanostructured pharmaceutical and cosmetic formulations using plants and their bioactive compounds.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Assessing quadriceps strength in patellofemoral pain patients: A study on the reliability and validity of a low-cost strain-gauge for clinical practice.

Patellofemoral pain (PFP) is a common knee complaint affecting diverse populations both acutely and chronically. Quadriceps muscle weakness is one possible aetiology, but current devices for measuring muscle strength (isokinetic dynamometer [ID] and hand-held dynamometers [HHD]) are frequently too expensive (e.g., ID) or lack reliability (e.g., HHD) for practitioners, especially in under-resourced settings. There is a need to evaluate a low-cost device to manage rehabilitation of people with PFP. Isometric quadriceps strength of participants aged 18-35 years (total [n = 33], control group [n = 17] and PFP group [n = 16]) were evaluated on an isokinetic dynamometer and a commercially available strain gauge at baseline and after an 8-week non-standardised intervention. The strain gauge showed high absolute and relative reliability (intraclass correlation coefficient = 0.89-0.99; typical error of measurement = 3.9-10.4%). Clinically meaningful difference scores (12.2-45 Nm) were greater than the typical error of measurement, implying sufficient sensitivity of the strain gauge to measure true changes in isometric quadricep strength. Strong to very strong correlations were evident between the strain gauge and isokinetic dynamometer torque measurements (r = 0.88-0.90, SEE = 0.05-0.07 Nm), but slope values (β = 0.65-0.77) indicated that torque from the strain gauge was lower than that obtained from the isokinetic dynamometer. An average systematic bias of 16.3-28.8 Nm was evident in favour of the isokinetic dynamometer, with no statistically significant between-group differences apparent between baseline and follow-up testing. The present commercially available strain gauge is reliable and sensitive enough to detect clinically meaningful differences in quadriceps strength of both healthy individuals and those with PFP. However, the strain gauge lacks validity and therefore cannot replace isokinetic dynamometry. Given the low cost and excellent reliability, the strain gauge can be a valuable tool to assess quadriceps muscle deficits and track rehabilitation progress in people with PFP.

Evaluation de la force musculaire chez le lombalgique chronique: Comparaison entre reeducation isocinetique et reeducation classique

Chronic low back pain is a public health problem in view of its functional repercussions and the functional rehabilitation is an integral part of its management. To compare the evolution of muscle strentgh of spinal extensors and flexors in chronic low back pain patients after an isokinetic rehabilitation protocol and a conventional rehabilitation one. This was a prospective and comparative study carried out in the Physical Medicine Department of the Tunis Military Hospital over a period of 7 months. Fifty patients were included, randomly divided into two groups of 25. The first group (G1) benefited from an isokinetic rehabilitation protocol and the second one (G2) from a classic active physiotherapy. We performed a clinical (Sorensen test and Shirado test) and isokinetic evaluation of the trunk muscles before and after rehabilitation. The mean age of the general population was 42±8.6 years old. Clinical evaluation showed a deficit in the extensor and flexor muscles of the spine, more important in the extensors in both groups. After rehabilitation, there was a significant improvement in clinical tests of muscular endurance in G1 and G2. Isokinetic assessment showed a greater muscle deficit in the extensors in both groups. After isokinetic rehabilitation, peak torque for flexors and extensors increased by 21% and 23% respectively, power was 34% and 37% higher, and total work increased by 26% and 47%. On the other hand, the (F/E) ratios were unchanged for all three speeds. In Group 2, peak torque values for flexors and extensors increased by 22 and 15% respectively, power was higher by 31 and 23% and total work was also up by 29 and 17%, while F/E ratios were also unchanged. Group 1 showed the greatest improvement in extensor strength at 60°/s, and in power at 90°/s for the various muscles. In our study, we concluded that endurance and muscular strength improved the most after isokinetic rehabilitation.

Investigator’s influence on the muscle strength assessment in animals in experiment: Comparison of automated “inverted grid” test and its classical variant

The aim of the work was to study the influence of the researcher on the muscle strength assessment in animals in the experiment by comparing the results of the automated “inverted grid” test and its classical variant.Materials and methods. Male lines (Bla/J, n=20; FUS(1-359), n=20; Tau P301S+/+, n=20) and their background controls (C57BL/6J, n=20; CD1, n=20) were selected for the study. The dynamics of changes in the muscle deficit of the animals was evaluated in the automated and classical variant of the “inverted grid” test.Results. According to the results of the muscle strength assessment of mice with an edited genome of lines FUS(1-359)+/-, Tau P301S+/+, B6.ADysfprmd/GeneJ, using the “inverted grid” test in the classical variant and the automated one, it was found that statistically significant differences were not obtained in comparison with the results obtained by the classical variant of the test. The standard error of the mean increases by 23–39% in the classical test compared to the automated one. It was shown that the standard error of the mean in the classical variant of the test in Tau P301S+/+ mice was 6.24; 5.94; 5.88; 7.38 at 4 age points; in FUS(1-359)+/- mice, 4.49; 6.8; 6.98 and 4.1; B6.ADysfprmd/GeneJ mice, 7.66; 7.58; 8.3 and 7.92, respectively.Conclusion. Thus, the value of the standard error of the results study mean of the changes dynamics in the muscle strength when using the automated variant of the “inverted grid” test was reduced in comparison with the results of the classical variant of the test. The results of the study show that the automation of generally recognized behavioral tests is able to increase the accuracy of the obtained data reducing the influence of a human factor on the manipulation.

Robotic thoracic surgery for neurogenic tumors.

Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors. This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients' medical and surgical records as well as radiological and pathological findings were analyzed. During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner's syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome. RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.

Tibial Bone Co-Morbidities Following Volumetric Muscle Loss Injury and Physical Inactivity

Volumetric muscle loss (VML) injuries are a traumatic loss of muscle, limiting regenerative potential and resulting in chronic loss of function. In isolation the bone adjacent to the VML injury is often overlooked, but known association between the tissues are important to long-term health and function. Recent work suggests decrements in both bones and muscles of VML-injured limbs, as well as a distinct relationship between VML and bone health. The clinically injured VML population is expected to undergo considerable periods of physical inactivity or a long-term sedentary lifestyle, and thus decreased loading, after VML. Our objective was to investigate the concomitant impact of VML on the adjacent bone, with and without the restriction of physical activity (reduced ~50% of daily ambulation). We hypothesized that with restriction of physical activity, the tibia adjacent to the VML would have functional impairments greater than those with normal physical activity (daily ambulation &gt;1km). Adult male C57BI/6J mice (n=41) underwent unilateral VML to the posterior hindlimb compartment or served as uninjured age-matched controls, then were randomized to standard or restricted activity cages for 8-wks. Terminally (age 20-wks), mice underwent in vivo muscle function testing. Adjacent tibia were assessed for strength, mid‐diaphysis cortical geometry, and intrinsic material properties, and the metaphyseal trabecular bone structure was evaluated by microcomputed tomography and three‐point bending. A subset of tibias was saved for histologic staining (H&amp;E, TRAP). Data were evaluated by two-way ANOVA. There were no absolute or normalized functional muscle deficits following 8-wks of inactivity. That said, there were significant VML-functional deficits (~42% of uninjured) that are not exacerbated by inactivity (p&lt;0.001). Cortical geometric changes in the bone were primarily a result of physical inactivity, with thickness and cross-sectional moment of inertia both diminished independent of injury (p≤0.018). However, there were no differences in cortical bone volume, diameter, or cross-sectional area (p≥0.056). Trabecular bone mineral density was lower in all VML-injured tibias compared to uninjured (p=0.003). While there was no difference across groups for trabecular spacing (p&gt;0.397), there was a reduction in bone mineral density across all VML-injured, compared to uninjured tibias (p=0.003). The functional capacity of the tibia to resist fracture (i.e., ultimate load during 3‐point bending) was ~21% lower with inactivity (p=0.018), while there was only a trend for VML injury to impact resistance to fracture. Stiffness was calculated during the onset to ultimate load and ~15% less in the VML injured and inactivity VML tibias (p=0.016). Tibia of VML injured and inactive groups appear to have greater lipid accumulation compared to uninjured tibias. While discordant with muscle function, physical activity restriction with and without VML injury impairs adjacent tibia. Inactivity alone had the greatest impact on the cortical bone properties, while VML with and without physical inactivity impacted trabecular tibia properties. This study demonstrates the impact of VML with and without physical inactivity on the tibia, furthering the complexity of traumatic injury on the musculoskeletal system. W81XWH‐20‐10885 (JAC &amp; SMG); S10OD025177. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lmod2 is necessary for effective skeletal muscle contraction.

Muscle contraction is a regulated process driven by the sliding of actin-thin filaments over myosin-thick filaments. Lmod2 is an actin filament length regulator and essential for life since human mutations and complete loss of Lmod2 in mice lead to dilated cardiomyopathy and death. To study the little-known role of Lmod2 in skeletal muscle, we created a mouse model with Lmod2 expressed exclusively in the heart but absent in skeletal muscle. Loss of Lmod2 in skeletal muscle results in decreased force production in fast- and slow-twitch muscles. Soleus muscle from rescued Lmod2 knockout mice have shorter thin filaments, increased Lmod3 levels, and present with a myosin fiber type switch from fast myosin heavy chain (MHC) IIA to the slower MHC I isoform. Since Lmod2 regulates thin-filament length in slow-twitch but not fast-twitch skeletal muscle and force deficits were observed in both muscle types, this work demonstrates that Lmod2 regulates skeletal muscle contraction, independent of its role in thin-filament length regulation.

Reorganization of mitochondria-organelle interactions during postnatal development in skeletal muscle.

Skeletal muscle cellular development requires the integrated assembly of mitochondria and other organelles adjacent to the sarcomere in support of muscle contractile performance. However, it remains unclear how interactions among organelles and with the sarcomere relates to the development of muscle cell function. Here, we combine 3D volume electron microscopy, proteomic analyses, and live cell functional imaging to investigate the postnatal reorganization of mitochondria-organelle interactions in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. Concomitantly, expression of proteins involved in mitochondria-organelle membrane contact sites decreases during postnatal development in tandem with a decrease in abundance of proteins associated with sarcomere assembly despite an overall increase in contractile protein abundance. Functionally, parallel measures of mitochondrial membrane potential, NADH redox status, and NADH flux within intact cells revealed that mitochondria in adult skeletal muscle fibres maintain a more activated electron transport chain compared with neonatal muscle mitochondria. These data demonstrate a developmental redesign reflecting a shift from muscle cell assembly and frequent inter-organelle communication toward a muscle fibre with mitochondrial structure, interactions, composition and function specialized to support contractile function. KEY POINTS: Mitochondrial network organization is remodelled during skeletal muscle postnatal development. The mitochondrial outer membrane is in frequent contact with other organelles at birth and transitions to more close associations with the contractile apparatus in mature muscles. Mitochondrial energy metabolism becomes more activated during postnatal development. Understanding the developmental redesign process within skeletal muscle cells may help pinpoint specific areas of deficit in muscles with developmental disorders.

Current approach in the follow-up treatment of joint-preserving operations on the knee joint in German-speaking countries

Postoperative follow-up after joint-preserving knee surgery involves conventional physiotherapy as well as other approaches and devices such as CPM and CAM splints, TENS devices, BFR exercise, prehabilitation, and digital health applications. The aim of this survey was to investigate current standards, trends and control methods in postoperative care to identify fields of concern and to compare them with the current literature. We conducted a structured anonymous online survey of specialists in orthopaedics and trauma surgery listed by the German-speaking Society for Arthroscopy and Joint Surgery (AGA). The questionnaire included 36 closed-ended questions on the follow-up of joint-preserving surgery of the knee joint. Questionnaires from 528 participants with long-term professional experience (86.6% with more than 10 years) were analysed. Standardised post-treatment schemes are used by 97.2% and their evidence is estimated to be high (59.1%) / very high (14.8%). Problems of rehabilitation are seen in 10-20% of cases by 87.3% (persistent muscular atrophy 30.9%). After reconstructive surgery, CPM splints (70.1%), CAM splints (42.1%), orthoses (85.0%) and TENS devices (40.0%) are prescribed. More potent approaches for the treatment of postoperative muscle deficits are desired by 89.4%. BFR exercise is known by 41.7% and is used regularly by 8%. Communication with treating physiotherapists is infrequent (written: 27.5%). Digital rehabilitation management would be supported by 83.3%; 22.7% are not aware of digital health applications. 87.9% of participants believe that prehabilitation can affect postoperative outcomes. Follow-up of knee joint-preserving surgeries is usually standardised and regularly reviewed for up-to-date evidence. The evidence for recommendations made is considered high. Orthoses are usually used after reconstructive surgery, persistent muscle atrophy is a major problem, BFR training is only known to a limited extent, and there is currently a lack of standardised training protocols. Communication with physiotherapists needs to be improved. Digital rehabilitation management is rarely used but would be supported by the majority of surgeons.

The Relative Efficacy of Available Proteasome Inhibitors in Preventing Muscle Contractures Following Neonatal Brachial Plexus Injury.

Contractures following neonatal brachial plexus injury (NBPI) are associated with growth deficits in denervated muscles. This impairment is mediated by an increase in muscle protein degradation, as contractures can be prevented in an NBPI mouse model with bortezomib (BTZ), a proteasome inhibitor (PI). However, BTZ treatment causes substantial toxicity (0% to 80% mortality). The current study tested the hypothesis that newer-generation PIs can prevent contractures with less severe toxicity than BTZ. Unilateral brachial plexus injuries were surgically created in postnatal (5-day-old) mice. Following NBPI, mice were treated with either saline solution or various doses of 1 of 3 different PIs: ixazomib (IXZ), carfilzomib (CFZ), or marizomib (MRZ). Four weeks post-NBPI, mice were assessed for bilateral passive range of motion at the shoulder and elbow joints, with blinding to the treatment group, through an established digital photography technique to determine contracture severity. Drug toxicity was assessed with survival curves. All PIs prevented contractures at both the elbow and shoulder (p < 0.05 versus saline solution controls), with the exception of IXZ, which did not prevent shoulder contractures. However, their efficacies and toxicity profiles differed. At lower doses, CFZ was limited by toxicity (30% to 40% mortality), whereas MRZ was limited by efficacy. At higher doses, CFZ was limited by loss of efficacy, MRZ was limited by toxicity (50% to 60% mortality), and IXZ was limited by toxicity (80% to 100% mortality) and loss of efficacy. Comparisons of the data on these drugs as well as data on BTZ generated in prior studies revealed BTZ to be optimal for preventing contractures, although it, too, was limited by toxicity. All of the tested second-generation PIs were able to reduce NBPI-induced contractures, offering further proof of concept for a regulatory role of the proteasome in contracture formation. However, the narrow dose ranges of efficacy for all PIs highlight the necessity of precise proteasome regulation for preventing contractures. Finally, the substantial toxicity stemming from proteasome inhibition underscores the importance of identifying muscle-targeted strategies to suppress protein degradation and prevent contractures safely. Although PIs offer unique opportunities to establish critical mechanistic insights into contracture pathophysiology, their clinical use is contraindicated in patients with NPBI at this time.

Insight into the Role of Gut Microbiota in Duchenne Muscular Dystrophy: An Age-Related Study in Mdx Mice

Dystrophindeficiency alters the sarcolemma structure, leading to muscle dystrophy, muscle disuse, and ultimately death. Beyond limb muscle deficits, patients with Duchenne muscular dystrophy have numerous transit disorders. Many studies have highlighted the strong relationship between gut microbiota and skeletal muscle. The aims of this study were: i) to characterize the gut microbiota composition over time up to 1 year in dystrophin-deficientmdxmice, and ii) to analyze the intestine structure and function and expression of genes linked to bacterial-derived metabolites in ileum, blood, and skeletal muscles to study interorgan interactions.Mdxmice displayed a significant reduction in the overall number of different operational taxonomic units and their abundance (α-diversity).Mdxgenotype predicted 20% ofβ-diversity divergence, with a large taxonomic modification of Actinobacteria, Proteobacteria, Tenericutes, and Deferribacteres phyla and the included genera. Interestingly, mdx intestinal motility and gene expressions of tight junction andFfar2receptor were down-regulated in the ileum. Concomitantly, circulating inflammatory markers relatedto gut microbiota (tumor necrosis factor, IL-6, monocyte chemoattractant protein-1) and muscle inflammationTlr4/Myd88pathway (Toll-like receptor 4, which recognizes pathogen-associated molecular patterns) were up-regulated. Finally, inmdxmice, adiponectin was reduced in blood and its receptor modulated in muscles. This study highlights a specific gut microbiota composition and highlights interorgan interactions inmdxphysiopathology with gut microbiota as the potential central metabolic organ.