Muscle Atrophy Research Articles

Mitigating disuse-induced skeletal muscle atrophy in ageing: Resistance exercise as a critical countermeasure.

The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due to the presence of 'anabolic resistance', resulting in muscle loss. Sarcopenia can be transiently but markedly accelerated through periods of muscle disuse-induced (i.e., unloading) atrophy due to reduced physical activity, sickness, immobilisation or hospitalisation. Periods of disuse are detrimental to older adults' overall quality of life and substantially increase their risk of falls, physical and social dependence, and early mortality. Disuse events induce skeletal muscle atrophy through various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis and mitochondrial dysfunction, all of which tip the scales in favour of a negative net protein balance and subsequent muscle loss. Concerningly, recovery from disuse atrophy is more difficult for older adults than their younger counterparts. Resistance training (RT) is a potent anabolic stimulus that can robustly stimulate muscle protein synthesis and mitigate muscle losses in older adults when implemented before, during and following unloading. RT may take the form of traditional weightlifting-focused RT, bodyweight training and lower- and higher-load RT. When combined with sufficient dietary protein, RT can accelerate older adults' recovery from a disuse event, mitigate frailty and improve mobility; however, few older adults regularly participate in RT. A feasible and practical approach to improving the accessibility and acceptability of RT is through the use of resistance bands. Moving forward, RT must be prescribed to older adults to mitigate the negative consequences of disuse atrophy.

A Cross-Sectional Validation of Horos and CoreSlicer Software Programs for Body Composition Analysis in Abdominal Computed Tomography Scans in Colorectal Cancer Patients.

Body composition assessment using computed tomography (CT) scans may be hampered by software costs. To facilitate its implementation in resource-limited settings, two open-source segmentation programs (Horos and CoreSlicer) were transversally validated in colorectal cancer patients. Contrast-enhanced abdominal CT scans were analyzed following the Alberta protocol. The Cross-Sectional Area (CSA) and intensities of skeletal muscle tissue (MT), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intramuscular adipose tissue (IMAT) were measured. The Skeletal Muscle Index (SMI) was calculated. Cutoff points were applied to the SMI, MT intensity, and VAT CSA to define muscle atrophy, myosteatosis, and abdominal obesity. The inter-software agreement was evaluated using different statistical tools. A total of 68 participants were measured. The MT CSA and SMI displayed no differences. The MT CSA agreement was excellent, and both programs provided equal muscle atrophy prevalences. CoreSlicer underestimated the MT intensity, with a non-significant myosteatosis prevalence increase (+5.88% and +8.82%) using two different operative definitions. CoreSlicer overestimated the CSA and intensity in both VAT and SAT, with a non-significant increase (+2.94%) in the abdominal obesity prevalence. Both software programs were feasible tools in the study group. The MT CSA showed great inter-software agreement and no muscle atrophy misdiagnosis. Segmentation differences in the MT intensity and VAT CSA caused limited diagnostic misclassification in the study sample.

Hybrid Training System Consisting of Synchronized Neuromuscular Electrical Stimulation for Voluntary Exercise Using an Articular Motion Sensor.

Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength, preventing muscle atrophy, and decreasing pain. Recently, NMES has become a substitute for exercise therapy for metabolism improvement and functional capacity improvement. However, NMES has several disadvantages. First, slow-twitch muscle contractions are insufficient because the recruitment pattern of NMES does not obey Henneman's size principle. Second, when using surface electrodes, it is difficult to contract deep skeletal muscles at the application site. Third, electrical stimulation causes discomfort. Therefore, we devised a simultaneous combination of NMES and voluntary muscle contractions to overcome the weak points of NMES. A hybrid training system (HTS) that resists the motion of a volitionally contracting agonist muscle with force generated by its electrically stimulated antagonist was developed as a technique to combine the application of NMES and volitional contractions. This motion sensor makes it possible to simultaneously combine voluntary movements with NMES. Our HTS synchronizes with voluntary movements, enhancing safety and reducing discomfort. This HTS enhances the exercise effect of even simple exercise. So far, our HTS has been reported to be effective for muscle strength enhancement, prevention of muscle atrophy, improvement of physical function, pain relief, enhancement of physical fitness, and improvement of metabolic function. HTS are expected to be useful methods in environments where sufficient exercise load is not available or for individuals with low exercise tolerance.

Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model.

Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low-frequency EMS (L-EMS, 10 Hz frequency), medium-frequency EMS (M-EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M-EMS group cell size was significantly larger than that of L-EMS and control group in both the immobilized and intact shoulders (all p < 0.05), without significant differences between the L-EMS and control groups. The M-EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all p < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M-EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M-EMS improved DMA with changes in the expression of relevant genes. M-EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery.

Comparative Analysis of Muscle Activity and Circulatory Dynamics: A Crossover Study Using Leg Exercise Apparatus and Ergometer.

Background and Objectives: Bedridden patients are at a high risk of venous thromboembolism (VTE). Passive devices such as elastic compression stockings and intermittent pneumatic compression are common. Leg exercise apparatus (LEX) is an active device designed to prevent VTE by effectively contracting the soleus muscle and is therefore expected to be effective in preventing disuse of the lower limbs. However, few studies have been conducted on the kinematic properties of LEX. Therefore, this study aimed to compare the exercise characteristics of LEX with those of an ergometer, which is commonly used as a lower-limb exercise device, and examine its effect on the two domains of muscle activity and circulatory dynamics. Materials and Methods: This study used a crossover design in which each participant performed both exercises to evaluate the exercise characteristics of each device. Fifteen healthy adults performed exercises with LEX and an ergometer (Terasu Erugo, SDG Co., Ltd., Tokyo, Japan) for 5 min each and rested for 10 min after each exercise. Muscle activity was measured using surface electromyography (Clinical DTS, Noraxon, Scottsdale, AZ, USA), and circulatory dynamics were recorded using a non-invasive impedance cardiac output meter (Physioflow Enduro, Manatec Biomedical, Paris, France). The primary outcome was the mean percentage of maximum voluntary contraction (%MVC) of the soleus muscle during exercise. Results: The mean %MVC of the soleus muscle was significantly higher in the LEX group, whereas no significant differences were observed across the periods and sequences. Heart rate, stroke volume, and cardiac output increased during exercise and decreased thereafter; however, the differences between the devices were not significant. Conclusions: LEX may not only have a higher thromboprophylaxis effect, but also a higher effect on preventing muscle atrophy as a lower-extremity exercise device. Additionally, LEX could potentially be used safely in patients who need to be monitored for changes in circulatory dynamics.

Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen.

Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.

Ultrasound-Compatible Electrode for Functional Electrical Stimulation.

Functional electrical stimulation (FES) is a vital method in neurorehabilitation used to reanimate paralyzed muscles, enhance the size and strength of atrophied muscles, and reduce spasticity. FES often leads to increased muscle fatigue, necessitating careful monitoring of the patient's response. Ultrasound (US) imaging has been utilized to provide valuable insights into FES-induced fatigue by assessing changes in muscle thickness, stiffness, and strain. Current commercial FES electrodes lack sufficient US transparency, hindering the observation of muscle activity beneath the skin where the electrodes are placed. US-compatible electrodes are essential for accurate imaging and optimal FES performance, especially given the spatial constraints of conventional US probes and the need to monitor muscle areas directly beneath the electrodes. This study introduces specially designed body-conforming US-compatible FES (US-FES) electrodes constructed with a silver nanowire/polydimethylsiloxane (AgNW/PDMS) composite. We compared the performance of our body-conforming US-FES electrode with a commercial hydrogel electrode. The findings revealed that our US-FES electrode exhibited comparable conductivity and performance to the commercial one. Furthermore, US compatibility was investigated through phantom and in vivo tests, showing significant compatibility even during FES, unlike the commercial electrode. The results indicated that US-FES electrodes hold significant promise for the real-time monitoring of muscle activity during FES in clinical rehabilitative applications.

Effects of Ulmus macrocarpa Extract and Catechin 7-O-β-D-apiofuranoside on Muscle Loss and Muscle Atrophy in C2C12 Murine Skeletal Muscle Cells.

Muscle atrophy is known to be one of the symptoms leading to sarcopenia, which significantly impacts the quality of life, mortality, and morbidity. Therefore, the development of therapeutics for muscle atrophy is essential. This study focuses on addressing muscle loss and atrophy using Ulmus macrocarpa extract and its marker compound, catechin 7-O-β-D-apiofuranoside, by investigating their effects on biomarkers associated with muscle cell apoptosis. Additionally, protein and gene expression in a muscle atrophy model were examined using Western blotting and RT-PCR. Ulmus macrocarpa has been used as food or medicine due to its safety, including its roots, barks, and fruit. Catechin 7-O-β-D apiofuranoside is an indicator substance of plants of the Ulmus genus and has been reported to have various effects such as antioxidant and anti-inflammatory effects. The experimental results demonstrated that catechin glycoside and Ulmus macrocarpa extract decreased the expression of the muscle-degradation-related proteins Atrogin-1 and Muscle RING-Finger protein-1 (MuRF1) while increasing the expression of the muscle-synthesis-related proteins Myoblast determination (MyoD) and Myogenin. Gene expression confirmation experiments validated a decrease in the expression of Atrogin and MuRF1 mRNA and an increase in the expression of MyoD and Myogenin mRNA. Furthermore, an examination of muscle protein expression associated with the protein kinase B (Akt)/forkhead box O (FoxO) signaling pathway confirmed a decrease in the expression of FoxO, a regulator of muscle protein degradation. These results confirm the potential of Ulmus macrocarpa extract to inhibit muscle apoptosis, prevent muscle decomposition, and promote the development of functional materials for muscle synthesis, health-functional foods, and natural-product-derived medicines.

RBP4 promotes denervation-induced muscle atrophy through STRA6-dependent pathway.

Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Denervation-induced muscle atrophy model was constructed in wild-type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) or oral gavage of RBP4 inhibitor A1120. Holo-RBP4-stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross-sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. The expression levels of RBP4 in skeletal muscles were significantly up-regulated more than 2-fold from 7days and sustained for 28days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation-induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin-1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol-bound holo-RBP4 aggregated denervation-induced ectopic fat accumulation and muscle atrophy. Consistently, holo-RBP4 stimulation also had a dose-dependent effect on the reduction of C2C12 myotube diameter and myofibre cross-sectional area, as well as on the increase of Atrogin-1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo-RBP4 treatment increased the expression of its membrane receptor STRA6 (>3-fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin-1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3-fold) in holo-RBP4-treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation-induced muscle atrophy (30% increased myofibre cross-sectional area) in mice. In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6-dependent and JAK2/STAT3 pathway-mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

Contrastive Disentanglement for Quantitative Ultrasound Muscle Atrophy Evaluation.

Muscleatrophy reduces the quality of life and increases morbidity and mortality from other diseases. The development of non-invasive muscle atrophy evaluation method is of great practical value. The lack of gold standard for pathological grading usually allows only the duration of weightlessness as a criterion for the degree of atrophy. However, the adaptive reductive remodeling of muscle physiology and structure shows a trend of nonlinear changes in time. Consequently, using weightlessness time as a benchmark for the degree of atrophy is inaccurate. This paper proposes a new ultrasound imaging-based method for quantifying muscle atrophy that utilizes weakly supervised information between multiple data partitions with controlled variance components, overcoming the limitations of using the weightlessness time as a criterion. We introduce a group-supervised contrastive disentanglement network (GCDNet) to disentangle the individual variances, muscle growth and atrophy components of ultrasound images, and quantify the degree of atrophy using the disentangled atrophy component. The feasibility of GCDNet is validated by the separability, independence, and representativeness of the disentangled components. To simplify the application of GCDNet, a muscle atrophy scoring network requiring no reference images is developed by distilling the GCDNet's knowledge of muscle atrophy quantization. The strength of the proposed methodology allows us, for the first time to our knowledge, to study the muscle growth attribute during hind-limb unloading and the spatial distribution of muscle atrophy.

Hounsfield units of vertebrae as a predictor of cervical deep paraspinal muscles atrophy and neck pain in degenerative cervical myelopathy.

This study investigated the correlation between Hounsfield units (HU) of the cervical vertebrae and atrophy of the cervical deep paraspinal muscles, namely the multifidus and semispinalis cervicis (SCer), in patients diagnosed with degenerative cervical myelopathy (DCM). The authors retrospectively analyzed data from 136 patients aged 50-79 years (81 males and 55 females) who underwent surgical intervention for DCM. HU measurements of the cancellous bone in the C4 vertebra were acquired through standardized techniques. The authors evaluated fatty infiltration (FI); analyzed functional and vertebral cross-sectional area (CSA) of the multifidus and SCer at the C4-5, C5-6, and C6-7 levels; and analyzed the presence of Modic changes (MCs) and the incidence of axial neck pain. Patients were categorized into group A (n = 56) with mean ± SD HU of 293.3 ± 15.6 and group B (n = 80) with mean ± SD HU of 389.5 ± 10.6. Both groups demonstrated significant improvements in postoperative clinical outcomes (p < 0.05); however, no statistically significant difference was observed (p > 0.05). Significant disparities in HU measurements and visual analog scale (VAS) scores for neck pain were observed between the groups (p < 0.05). The highest VAS score correlated with MCs-1 type (i.e., low signal on T1-weighted images and high signal on T2-weighted images). The functional CSA to vertebral CSA ratios of the multifidus and SCer in group A were markedly reduced compared to those of group B (p < 0.05). No significant difference was noted in functional CSA asymmetry between the groups for both muscles (p > 0.05). Lower HU measurements directly correlated with increased FI in the multifidus (p = 0.002) and SCer (p = 0.035). Furthermore, a strong positive association was found between the functional CSA to vertebral CSA ratio of the multifidus and HU values (p = 0.003), whereas HU measurements and VAS scores exhibited a negative correlation (p = 0.020). Among those patients older than 50 years with DCM, those with decreased HU values demonstrated elevated FI levels in the multifidus and SCer muscles. Moreover, these patients presented with pronounced muscle atrophy, which correlated with axial neck pain. A significant relationship was also identified between MCs and diminished HU values.

Qualitative analysis of the Supraspinatus muscle fatty infiltration on MRI - Correlation of the Tangent sign with Goutallier grade at the Y view and Medial Scapular border in large retracted rotator cuff tears

BackgroundSurgically repairing rotator cuff tears with a higher extent of fatty infiltration is controversial. Current evidence supports performing rotator cuff repair in patients exhibiting Goutallier stage 3-4 fatty infiltration. However, the presence of retraction complicates accurate assessment using the Goutallier Classification, particularly on the lateral Y-view. A shift towards classifying fatty infiltration in more medial regions may enhance the precision of tissue quality quantification. The objective of this study was to analyze the uniformity of fatty infiltration within the entire supraspinatus muscle using the Goutallier Classification across three scapular Y-view sections and to examine the association between Goutallier grade, tangent sign, and modified Patte stage. MethodsA retrospective evaluation was conducted on preoperative magnetic resonance imaging (MRI) scans from a consecutive series of 97 patients who had previously undergone arthroscopic rotator cuff repairs. Three supraspinatus sections on the MRI sagittal plane were identified: the lateral Y-view (section one), a medial section at the suprascapular notch anatomical landmark (section two), and a section 3 cm medial from the suprascapular notch Medial Scapular Body (section three). Goutallier grade, tangent sign, and modified Patte stage were used to evaluate fatty infiltration, muscle atrophy, and tendon retraction, respectively. ResultsSection one had the highest Goutallier grade, while section three had the lowest. Intra-observer rest retest reliability analysis showed excellent consistency in all sections with section one (ICC=0.920, 95% CI), section two (ICC=0.917, 95% CI), and section three (ICC=0.923, 95% CI) for Goutallier grade. Inter-observer reliability analysis also revealed excellent consistency in sections one (ICC=0.951, 95% CI), section two (ICC=0.949, 95% CI), and section three (ICC=0.922, 95% CI) for Goutallier grade. A strong correlation was observed between Goutallier grade and modified Patte stage (τb=0.43-0.56, p=0.001), and between Goutallier grade and tangent sign (τb=0.43-0.54, p=0.001) across all sections. ConclusionThe severity of fatty infiltration within the supraspinatus muscle belly is inconsistent, with the lateral portion being the most severe and the medial portion the least severe. Goutallier grade demonstrates a strong correlation with tangent sign and modified Patte stage. This suggests that tendon retraction results in a potential overestimation in the amount of fatty infiltration defining some tears unjustly irreparable when measuring at the traditionally described lateral Y-view position compared with 3cm medial.

Murf1 alters myosin replacement rates in cultured myotubes in a myosin isoform-dependent manner.

Skeletal muscle tissue increases or decreases its volume by synthesizing or degrading myofibrillar proteins. The ubiquitin-proteasome system plays a pivotal role during muscle atrophy, where muscle ring finger proteins (Murf) function as E3 ubiquitin ligases responsible for identifying and targeting substrates for degradation. Our previous study demonstrated that overexpression of Ozz, an E3 specific to embryonic myosin heavy chain (Myh3), precisely reduced the Myh3 replacement rate in the thick filaments of myotubes (E. Ichimura et al., Physiol Rep. 9:e15003, 2021). These findings strongly suggest that E3 plays a critical role in regulating myosin replacement. Here, we hypothesized that the Murf isoforms, which recognize Myhs as substrates, reduced the myosin replacement rates through the enhanced Myh degradation by Murfs. First, fluorescence recovery after a photobleaching experiment was conducted to assess whether Murf isoforms affected the GFP-Myh3 replacement. In contrast to Murf2 or Murf3 overexpression, Murf1 overexpression selectively facilitated the GFP-Myh3 myosin replacement. Next, to examine the effects of Murf1 overexpression on the replacement of myosin isoforms, Cherry-Murf1 was coexpressed with GFP-Myh1, GFP-Myh4, or GFP-Myh7 in myotubes. Intriguingly, Murf1 overexpression enhanced the myosin replacement of GFP-Myh4 but did not affect those of GFP-Myh1 or GFP-Myh7. Surprisingly, overexpression of Murf1 did not enhance the ubiquitination of proteins. These results indicate that Murf1 selectively regulated myosin replacement in a Myh isoform-dependent fashion, independent of enhanced ubiquitination. This suggests that Murf1 may have a role beyond functioning as a ubiquitin ligase E3 in thick filament myosin replacement.

The Impact of Nusinersen and Risdiplam on Motor Function for Spinal Muscular Atrophy Type 2 and 3: A Meta-Analysis.

Spinal muscular atrophy (SMA) is a prevalent paediatric neuromuscular disorder characterised by muscle weakness and atrophy resulting from degeneration of spinal cord anterior horn α motor neurons. Gene therapy formulations exhibit varying benefits and limitations, driving the need for patient-friendly treatment options tailored to specific populations. The objective of this meta-analysis was to assess the effectiveness of gene therapy for motor function in children with SMA. The analysis encompassed a total of 719 participants from six randomised controlled trials (RCTs) conducted between 2017 and 2023. Among the studies, one demonstrated a significant and large standardised effect size (Cohen's d) favouring nusinersen in terms of Hammersmith Functional Motor Scale - Expanded (HFMSE) (d = 0.97) and revised upper limb module (RULM) (d = 0.96). Additionally, another study showed a moderate standardised effect size (Cohen's d) in favour of nusinersen concerning Hammersmith Infant Neurological Examination-Section 2 (HINE-2) (d = 0.48). However, it is important to note that further research with a longer duration of observation is required to strengthen the evidence. Key Words: Spinal muscular atrophy, Nusinersen, Risdiplam, Motor function, Cohen's d.

A novel variant in the GNE gene in a Malian patient presenting with distal myopathy.

GNE-myopathy (GNE-M) is a rare autosomal recessive disorder caused by variants in the GNE gene. We report a novel variant in GNE causing GNE-M in a Malian family. A 19-year-old male patient from consanguineous marriage was seen for progressive walking difficulty. Neurological examination found predominant distal muscle weakness and atrophy, decreased tendon reflexes, predominating in lower limbs. Electroneuromyography showed an axonal neuropathy pattern. However, whole exome sequencing (WES) revealed a novel biallelic variant in GNE c.1838G > A:p.Gly613Glu, segregating with the phenotype within the family. This study highlights its diagnosis challenges in sub-Saharan Africa and broadens the genetic spectrum of this rare disease.

Repeated birth injuries lead to long-term pelvic floor muscle dysfunction in the preclinical rat model

ObjectivesVaginal childbirth is a key risk factor for pelvic floor muscle injury and dysfunction, and subsequent pelvic floor disorders. Multiparity further exacerbates these risks. Using the rat model, validated for the studies of the human pelvic floor muscles, we have previously identified that a single simulated birth injury results in pelvic floor muscle atrophy and fibrosis. We hypothesized that multiple birth injuries would further overwhelm the muscle regenerative capacity, leading to functionally relevant pathological alterations long-term. Study DesignSprague-Dawley rats underwent simulated birth injury and were allowed to recover for 8 weeks before undergoing additional birth injury. Animals were sacrificed at acute (3- and 7-days post injury), subacute (21-, 28-, and 35-days post-injury), and long-term (8- and 12-weeks post-injury) time points post-second injury (N=3-8/time point), and the pubocaudalis portion of the rat levator ani complex was harvested to assess the impact of repeated birth injuries on muscle mechanical and histomorphological properties. The accompanying transcriptional changes were assessed by a customized NanoString panel. Uninjured animals were used as controls. Data with a parametric distribution were analyzed by a two-way analysis of variance followed by post hoc pairwise comparisons using Tukey’s or Sidak’s tests; non-parametrically distributed data were compared with Kruskal-Wallis test followed by pairwise comparisons with Dunn’s test. Data, analyzed using GraphPad Prism v8.0, San Diego, CA, are presented as mean ± SEM or median (range). ResultsFollowing the 1st simulated birth injury, active muscle force decreased acutely relative to uninjured controls (12.9±0.9 vs 25.98±2.1 g/mm2, P<0.01). At 4 weeks, muscle active force production recovered to baseline and remained unchanged at 8 weeks after birth injury (P>0.99). Similarly, precipitous decrease in active force was observed immediately after repeated birth injury (18.07±1.2 vs 25.98±2.1 g/mm2, P<0.05). In contrast to the functional recovery after a single birth injury, a long-term decrease in muscle contractile function was observed up to 12 weeks after repeated birth injuries (18.3±1.6 vs 25.98±2.1 g/mm2, P<0.05). Fiber size was smaller at the long-term time points after 2nd injury compared to the uninjured group (12 weeks vs uninjured control: 1485 (60.7-5000) vs 1989 (65.6-4702) μm2, P<0.0001). The proportion of fibers with centralized nuclei, indicating active myofiber regeneration, returned to baseline at 8 weeks post-1st birth injury, (P=0.95), but remained elevated as far as 12 weeks post-2nd injury (12 weeks vs uninjured control: 7.1±1.5 vs 0.84±0.13%, P<0.0001). In contrast to the plateauing intramuscular collagen content after 4 weeks post-1st injury, fibrotic degeneration increased progressively over 12 weeks after repeated injury (12 weeks vs uninjured control: 6. 7±1.1 vs 2.03±0.2%, P<0.001). Prolonged expression of pro-inflammatory genes accompanied by a greater immune infiltrate was observed after repeated compared to a single birth injury. ConclusionsOverall, repeated birth injuries led to a greater magnitude of pathological alterations compared to a single injury, resulting in more pronounced pelvic floor muscle degeneration and muscle dysfunction in the rat model. The above provides a putative mechanistic link between multiparity and the increased risk of pelvic floor dysfunction in women.

Relationship between Lumbar Foraminal Stenosis and Multifidus Muscle Atrophy - A Retrospective Cross-Sectional Study.

Retrospective cross-sectional study. To evaluate the relationship between lumbar foraminal stenosis (LFS) and multifidus muscle atrophy. The multifidus muscle is an important stabilizer of the lumbar spine. In LFS, the compression of the segmental nerve can give rise to radicular symptoms and back pain. LFS can impede function and induce atrophy of the segmentally innervated multifidus muscle. Patients with degenerative lumbar spinal conditions who underwent posterior spinal fusion for degenerative lumbar disease from December 2014 to February 2024 were analyzed. Multifidus fatty infiltration (FI) and functional cross-sectional area (fCSA) were determined at the L4 upper endplate axial level on T2- weighted MRI scans using dedicated software. Severity of LFS was assessed at all lumbar levels and sides using the Lee classification (Grade: 0 - 3). For each level, Pfirrmann and Weishaupt gradings were used to assess intervertebral disc disease (IVDD) and facet joint osteoarthritis (FJOA), respectively. Multivariable linear mixed models were run for the LFS grade of each level and side separately as the independent predictor of multifidus FI and fCSA. Each analysis was adjusted for age, sex, BMI, as well as FJOA and IVDD of the level corresponding to the LFS. A total of 216 patients (50.5% female) with a median age of 61.6 years (IQR=52.0 - 69.0) and a median BMI of 28.1kg/m2 (IQR=24.8 - 33.0) were included. Linear mixed model analysis revealed that higher multifidus FI (Estimate [Confidence interval]=1.7% [0.1 - 3.3], P=0.043) and lower fCSA (-18.6mm2 [-34.3 - -2.6], P=0.022) were both significantly predicted by L2-L3 level LFS severity. The observed positive correlation between upper segment LFS and multifidus muscle atrophy points towards compromised innervation. This necessitates further research to establish the causal relationship and guide prevention efforts.

Consensus Recommendations for Neurogenic Thoracic Outlet Syndrome from the INTOS Workgroup.

There is significant variation in methods used for diagnosis and treatment of neurogenic thoracic outlet syndrome (NTOS). The lack of definitions and criteria for diagnosis as well as controversy in treatment options hampers standardized reporting of outcomes. In the orthopedic and plastic hand surgery literature, there are not standardized guidelines to direct evidence-based practice for hand surgeons relating to NTOS. Hence, expert consensus may provide guidance for clinical practice. An international workgroup of 21 expert hand surgeons with cumulative experience of 5519 NTOS procedures was assembled. The Delphi method was used to arrive at consensus recommendations to guide diagnosis, treatment, surgery, and postoperative management of patients with NTOS. The workgroup achieved majority (greater than 75%) consensus with 17 statements. A modified version of the Society for Vascular Surgery clinical diagnostic criteria is recommended for diagnosis of NTOS. The elevated arm stress test and Tinel sign are recommended as provocative maneuvers. A cervical spine or chest radiograph should be routinely obtained preoperatively. Conservative management should be first line for NTOS, except in patients with significant muscle atrophy or weakness. An anterior supraclavicular approach is recommended for exposure of the supraclavicular brachial plexus, with the necessity for an additional infraclavicular approach or adjunctive surgeries indicated for specific patients. Standardized consensus guidelines help guide management of NTOS by specialized hand surgeons, with an aim toward standardizing criteria for diagnosis and treatment of patients as well as measures and tools used for research and reporting of outcomes.

Cardiovascular effects of long-duration space flight.

Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

SCOPING: A Pilot Study Exploring the Role of A Series of Clinical Observational Parameters as Indicators of Nerve Regeneration.

Following the repair of a mixed peripheral nerve, functional recovery requires successful nerve regeneration across the repair site and, eventually, reinnervation of distal targets. Reliably determining a failing nerve repair so that revision may be performed before irreversible muscle atrophy remains a challenge in peripheral nerve surgery. This study aimed to ascertain whether any commonly used clinical examination tests during surveillance after nerve repair can detect a failing repair and prompt earlier salvage intervention. A prospective observational cohort study was performed to evaluate commonly used clinical determinants of neuron regeneration that may provide early surrogate recovery measures. Sequential cutaneous thermography was used to identify temperature differences between denervated and normal skin in the hand operated on, with the contralateral hand as a control. Six out of nine patients completed between 6 and 18 months of follow-up. Tinel sign progression was observed in all subjects. Tinel progression rate was associated with motor and sensory Medical Research Council grade. The delta temperature was calculated to document the size and direction of any temperature differentials in the hand detected by thermography, but we did not have sufficient data to calculate any correlations with motor and sensory Medical Research Council grade. Specifically, the progression of Tinel sign is associated with recovery measured by progression of the British Medical Research Council motor and sensory grades. The use of thermographic imaging demonstrates that there is a difference in temperature between an injured and noninjured nerve. Future studies could investigate to what extent thermographic imaging predicts final nerve repair outcomes.