Control Of Muscle Research Articles

Assessing safety, efficacy and residue depletion in golden mahseer, Tor putitora (Hamilton, 1822): biochemical and physiological responses to graded concentrations of oxytetracycline dietary supplementation.

The safety and effectiveness of oxytetracycline can potentially manage bacterial infections in fish. This, in turn, might reduce the concerns related to its use in aquaculture and human consumption, such as toxicity, antimicrobial resistance, and other associated risks. The primary objective of this study was to assess how adding oxytetracycline dihydrate to the diet affects its effectiveness, safety, and the presence of residues in T. putitora. T. putitora fingerlings, subjected to experimental infection with Aeromonas hydrophila at a concentration of 108 CFU mL- 1, received an oral administration of oxytetracycline dihydrate. The oxytetracycline dihydrate was added to the feed (corresponding to 2% of the fish body weight) at concentrations of 44.1, 88.2, 132.3 and 176.4mg Kg- 1 fish body weight per day. This treatment was carried out for 10 consecutive days. The biochemical and physiological responses of T. putitora and efficacy of oxytetracycline dihydrate were determined through estimation of microbial load (CFU mL- 1), haematogram, serum biomarkers, behavioral characteristics, non-specific immunity and residue depletion. Experimentally infected fish showed disease progression and induced histopathological conditions with highest microbial load (CFU mL- 1) in the muscle of both control and treated fish. The fish haematogram showed increased leucocyte and haemoglobin content, influenced by dietary oxytetracycline dihydrate. The fish demonstrated adaptive physiological response to oxytetracycline dihydrate at 44.1 to 88.2mg and resulted in increased albumin and globulin content. The serum-enzyme assay showed significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and plasma alkaline phosphatase (ALP) activities in the test fish (< 0.05). Oxytetracycline dihydrate at 88.2 to 132.3mg Kg- 1 fish body weight per day recorded higher feed intake (75%), significant survivability (66-68%) and histopathological recovery. The suppressed immune response was manifested with decreased respiratory burst and lysozyme activity. The palatability, treatment of bacterial infection, histopathological changes and survivability by fingerlings of golden mahseer determined the safety and optimized the therapeutic potential of the oxytetracycline dihydrate at 88.2mg Kg- 1 fish body weight per day for 10 days to contain the infection by A. hydrophila. A withdrawal period of 8-d was recommended as oxytetracycline dihydrate concentration depleted below the legal maximum residue limit (MRL 2.0 mg g- 1) in the edible muscle of the golden mahseer reared at an average water temperature of 20°C. This is considered safe for human consumption.

Mechanical interaction of myosin and native thin filament in the disused rat soleus muscle

The disuse of skeletal limb muscles occurs in a variety of conditions, yet our comprehension of the molecular mechanisms involved in adaptation to disuse remains incomplete. We studied the mechanical characteristics of actin-myosin interaction using an in vitro motility assay and isoform composition of myosin heavy and light chains by dint of SDS-PAGE in soleus muscle of both control and hindlimb-unloaded rats. 14 days of hindlimb unloading led to the increased maximum sliding velocity of actin, reconstituted, and native thin filaments over rat soleus muscle myosin by 24 %, 19 %, and 20 %, respectively. The calcium sensitivity of the “pCa-velocity” relationship decreased. There was a 26 % increase in fast myosin heavy chain IIa (MHC IIa), a 22 % increase in fast myosin light chain 2 (MLC 2f), and a 13 % increase in fast MLC 1f content. The content of MLC 1s/v, typical for slow skeletal muscles and cardiac ventricles did not change. At the same time, MLC 1s, typical only for slow skeletal muscles, disappeared. The maximum velocity of soleus muscle native thin filaments was 24 % higher compared to control ones sliding over the same rabbit myosin. Therefore, both myosin and native thin filament kinetics could influence the mechanical characteristics of the soleus muscle. Additionally, the MLC 1s and MLC 1s/v ratio may contribute to the mechanical characteristics of slow skeletal muscle, along with MHC, MLC 2, and MLC 1 slow/fast isoforms ratio.

Running improves muscle mass by activating autophagic flux and inhibiting ubiquitination degradation in mdx mice

BackgroundExercise therapy can improve muscle mass, strengthen muscle and cardiorespiratory function, and may be an excellent adjunctive treatment option for Duchenne muscular dystrophy. MethodsThis article investigates the effects of 10 weeks of treadmill training on skeletal muscle in control and mdx mice. Hematoxylin and eosin (H&E) staining was used to detect the morphometry of skeletal muscle; the grip strength test, suspension test, and rotarod test were used to detect limb muscle strength of mice, and Aurora Scientific Instruments were used to detect in vivo Muscle Stimulation Measuring Maximum Force of pre-fatigue and post-fatigue. The expression levels of myogenic proteins, ubiquitination markers, autophagy pathway proteins, and the proportion of different muscle fiber types were detected. ResultsThe experimental results show that running exercise can significantly improve the muscle mass of mdx mice, promote muscle strength, endurance, and anti-fatigue ability, reverse the pathological state of skeletal muscle destruction in mdx mice, and promote muscle regeneration. WB experiments showed that running inhibited the ubiquitination and degradation of muscle protein in mdx mice, inhibited AKT activation, decreased phosphorylated FoxO1 and FoxO3a, and restored the suppressed autophagic flux. Running enhances muscle strength and endurance by comprehensively promoting the expression of Myh1/2/4/7 fast and slow muscle fibers in mdx mice. ConclusionsRunning can inhibit the degradation of muscle protein in mdx mice, and promote the reuse and accumulation of proteins, thereby slowing down muscle loss. Running improves skeletal muscle mass by activating autophagic flux and inhibiting ubiquitination degradation in mdx mice.

Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins.

Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. Here, we examine the properties of OLPVR1 (Organic Lake Phycodnavirus Rhodopsin) and two other type 1 viral channelrhodopsins (VCR1s), and demonstrate that VCR1s accumulate exclusively intracellularly, and, upon illumination, induce calcium release from intracellular IP3-dependent stores. In vivo, this light-induced calcium release is sufficient to remote control muscle contraction in VCR1-expressing tadpoles. VCR1s natively confer light-induced Ca2+ release, suggesting a distinct mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as potential precursors for optogenetics tools, with potential applications in basic research and medicine.

Association between quadriceps tendon elasticity and neuromuscular control in individuals with knee osteoarthritis

BackgroundKnee osteoarthritis is a complex condition with established risk factors such as female sex, increasing age and body mass index, reduced quadriceps muscle strength and knee injury. Despite known associated risks, the role and behaviour of knee tendons in knee osteoarthritis remains unclear. This study explores the association between quadriceps tendon elasticity, muscle strength, neuromuscular control, proprioception and patient reported outcome measures in individuals with knee osteoarthritis. MethodsAdults with doctor-diagnosed knee osteoarthritis were recruited from rheumatology clinics and general practitioner practices. Quadriceps tendon elasticity was estimated using sonoelastography. Neuromuscular control data including electromyography, electromechanical delay and proprioception measures were included. Participants completed the Knee Injury and Osteoarthritis Outcome Score. Associations between elasticity values, physical and neuromuscular data and patient reported outcomes scores were evaluated using Spearman's correlations. FindingsThirty-nine adults with knee osteoarthritis were eligible for inclusion. Increased tendon stiffness was negatively associated with rate of force development, time to half peak force and passive positioning sense in individuals with knee osteoarthritis. Similarly, patient reported symptoms were found to be associated with sonoelastography findings with moderate-strong associations observed between activities of daily living sport and recreation, pain and symptoms and between neuromuscular control measures and muscle strength. InterpretationStiffer tendon identified within the knee osteoarthritis group was associated with reduced neuromuscular control and knee joint proprioception. Stiffer quadriceps tendon may contribute to the poorer reported symptoms by knee osteoarthritis individuals. These findings may impact disease symptoms and progression which could lead to further joint impairment.

Nuclear pore pathology underlying multisystem proteinopathy type 3-related inclusion body myopathy.

Multisystem proteinopathy type 3 (MSP3) is an inherited, pleiotropic degenerative disorder caused by a mutation in heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which can affect the muscle, bone, and/or nervous system. This study aimed to determine detailed histopathological features and transcriptomic profile of HNRNPA1-mutated skeletal muscles to reveal the core pathomechanism of hereditary inclusion body myopathy (hIBM), a predominant phenotype of MSP3. Histopathological analyses and RNA sequencing of HNRNPA1-mutated skeletal muscles harboring a c.940G > A (p.D314N) mutation (NM_031157) were performed, and the results were compared with those of HNRNPA1-unlinked hIBM and control muscle tissues. RNA sequencing revealed aberrant alternative splicing events that predominantly occurred in myofibril components and mitochondrial respiratory complex. Enrichment analyses identified the nuclear pore complex (NPC) and nucleocytoplasmic transport as suppressed pathways. These two pathways were linked by the hub genes NUP50, NUP98, NUP153, NUP205, and RanBP2. In immunohistochemistry, these nucleoporin proteins (NUPs) were mislocalized to the cytoplasm and aggregated mostly with TAR DNA-binding protein 43 kDa and, to a lesser extent, with hnRNPA1. Based on ultrastructural observation, irregularly shaped myonuclei with deep invaginations were frequently observed in atrophic fibers, consistent with the disorganization of NPCs. Additionally, regarding the expression profiles of overall NUPs, reduced expression of NUP98, NUP153, and RanBP2 was shared with HNRNPA1-unlinked hIBMs. The shared subset of altered NUPs in amyotrophic lateral sclerosis (ALS), as demonstrated in prior research, HNRNPA1-mutated, and HNRNPA1-unlinked hIBM muscle tissues may provide evidence regarding the underlying common nuclear pore pathology of hIBM, ALS, and MSP.

Comparing the Impact of Upper Body Control and Core Muscle Stabilization Training on Landing Biomechanics in Individuals with Functional Ankle Instability: A Randomized Controlled Trial.

Functional ankle instability (FAI), which is characterized by recurrent ankle sprains and perceived joint instability, arises from various factors contributing to compromised biomechanical control during activities, particularly those involving landing tasks. While current research predominantly addresses lower-extremity and core stabilization interventions for FAI, the contribution of upper body control to landing biomechanics in this population remains insufficiently explored. In this study, 42 participants (19 males, 23 females) with FAI were randomly assigned to either the upper-body control training group (UBCTG) or the core muscle stabilization training group (CMSTG). The groups underwent six-week interventions, with the UBCTG receiving a dynamic core exercise program including upper body control and the CMSTG receiving static core muscle training. Pre- and post-intervention assessments encompassed electromyography of the gastrocnemius, tibialis anterior, and peroneus longus, motion analysis of the lower extremities, and ground reaction force (GRF) readings during a single-leg-jump task. Additionally, dynamic balance was assessed using the Y balance test and self-reported measurements of ankle instability were performed. The results showed similar increases in muscle activation, joint movement, and self-reported ankle instability scores within both groups. However, significant between-group differences were observed in terms of knee flexion angle, dynamic balance, and ankle instability scores, favoring the UBCTG. Although the peak vertical GRF significantly decreased and the time to peak vertical GRF increased in both groups, more changes were noted in the UBCTG. Our results demonstrated that dynamic core exercises with additional upper body control training enhance landing biomechanics, dynamic balance, and stability in individuals with FAI. Consequently, we recommend incorporating shoulder girdle exercises, proprioceptive drills, and balance exercises into dynamic core training.

Prefrontal cortex hemodynamic activity during a test of lower extremity functional muscle strength in children with cerebral palsy: A functional near-infrared spectroscopy study.

Children with cerebral palsy (CP) exhibit impaired motor control and significant muscle weakness due to a brain lesion. However, studies that assess the relationship between brain activity and performance on dynamic functional muscle strength assessments in CP are needed. The aim of this study was to determine the effect of a progressive lateral step-up test on prefrontal cortex (PFC) hemodynamic activity in children with CP. Fourteen ambulatory children with spastic CP (Gross Motor Function Classification System level I; 5-11 y) and 14 age- and sex-matched typically developing control children completed a progressive lateral step-up test at incremental step heights (0, 10, 15 and 20 cm) using their non-dominant lower limb. Hemodynamic activity in the PFC was assessed using non-invasive, portable functional neuroimaging (functional near-infrared spectroscopy). Children with CP completed fewer repetitions at each step height and exhibited lower PFC hemodynamic activity across step heights compared to controls. Lower PFC activation in CP was maintained after statistically controlling for the number of repetitions completed at each step height. PFC hemodynamic activity was not associated with LSUT task performance in children with CP, but a positive relationship was observed in controls at the most challenging 20 cm step height. The results suggest there is an altered PFC recruitment pattern in children with CP during a highly dynamic test of functional strength. Further studies are needed to explore the mechanisms underlying the suppressed PFC activation observed in children with CP compared to typically developing children.

EFFECT OF ACUTE FOAM ROLLER AND PERCUSSION THERAPY ON MUSCLE ARCHITECTURE AND MUSCLE STIFFNESS

The aim of the study is to investigate the effect of the acute application of foam roller and massage gun, which are self-myofascial techniques, on muscle architecture and muscle stiffness. 27 male athletes participated in the study. Within the scope of the study, the athletes were randomly divided into 3 groups as 1st group foam roller (FR), 2nd group massage gun (MG), 3rd group as control group (CG) and muscle architecture and muscle stiffness (MS) were evaluated as a result of acute exercise. Muscle stiffness (MS) muscle thickness (MT), cross-sectional area (CSA), and pennate angles (PA) of the subjects were measured by ultrasound. The measurement results were tested with repeated measures two-way Anova test analysis of variance in the SPSS program, and significance was accepted as p&amp;lt;0.05. When the measurement results of MS, PA, and MT were examined, no significant difference was observed in the FR, MG, and CG pre-test and post-test (p= 0.94). In the pretest and posttest results of the CSA of the muscle, a decrease was observed in the FR group and an increase in the MG group (p=0.03). In conclusion; shows that muscle thickness,pennation angle, and muscle stiffness do not change after acute self-myofascial relaxations and that foam roller and massage gun do not have superiority over each other. The cross-sectional area decreased after the foam roller application and increased after the massage gun.

Fenpropathrin Induces Oxidative Stress, Inhibits Cholinesterase, and Causes Genotoxicity in &lt;i&gt;Pethia conchonius&lt;/i&gt; (Hamilton, 1822)

Pesticide contamination in water bodies is a serious threat to aquatic organisms. Among the new generation pesticides, synthetic pyrethroids enter the aquatic environment from agricultural runoff and are more persistent in aquatic environment. In this study, we investigated the effect of fenpropathrin, a type II pyrethroid, on Pethia conchonius. The median lethal concentration for commercial formulation of fenpropathrin (Danitol®) was determined to be 2.43 μg/L. Based on the median lethal concentration, the fish were exposed to 1/5th (0.486 μg/L) and 1/10th (0.243 μg/L) of median lethal concentrations for 30 days. After the exposure period, antioxidant enzymes status (superoxide dismutase and catalase), oxidative stress parameters (lipid peroxidation and reduced glutathione) in brain, liver, and kidney, cholinesterase enzyme activity in brain and muscles, and incidences of micronucleus were evaluated. In the treatment groups, alteration in antioxidant enzyme levels were observed in brain, liver, and kidney. Lipid peroxidation, which is indicative of oxidative stress, was observed but did not show much variation. Reduced glutathione was also altered. Cholinesterase activity was significantly different in the brain tissues between control and treatment groups; however, no significant difference was observed between the cholinesterase activities of muscles in control and treatment groups. Micronucleus incidence in treatment groups was higher than that in the control. Our study indicates that fenpropathrin altered the antioxidative enzyme status, inhibited cholinesterase activity in brain, and exhibited potential genotoxic effects in the fish Pethia conchonius.

High-frequency Quantitative Ultrasound Imaging of Human Rotator Cuff Muscles: Assessment of Repeatability and Reproducibility.

This study evaluated the repeatability and reproducibility of using high-frequency quantitative ultrasound (QUS) measurement of backscatter coefficient (BSC), grayscale analysis, and gray-level co-occurrence matrix (GLCM) textural analysis, to characterize human rotator cuff muscles. The effects of varying scanner settings across two different operators and two US systems were investigated in a healthy volunteer with normal rotator cuff muscles and a patient with chronic massive rotator cuff injury and substantial muscle degeneration. The results suggest that BSC is a promising method for assessing rotator cuff muscles in both control and pathological subjects, even when operators were free to adjust system settings (depth, level of focus, and time-gain compensation). Measurements were repeatable and reproducible across the different operators and ultrasound imaging platforms. In contrast, grayscale and GLCM analyses were found to be less reliable in this setting, with significant measurement variability. Overall, the repeatability and reproducibility measurements of BSC indicate its potential as a diagnostic tool for rotator cuff muscle evaluation.

LOCAL AND SYSTEMIC MEDIATORS OF SKELETAL MUSCLE WASTING IN HUMANS FOLLOWING ACUTE TRAUMA

AbstractIntroductionSkeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited.ObjectivesTo characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma.MethodsExperiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P&lt;0.05.ResultsThere was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P&lt;0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in muscle of trauma patients vs controls (0.5 and 0.39-fold respectively; P&lt;0.05). In serum, trauma patients showed increased concentrations of circulating pro-inflammatory cytokines IL-6 (14.5 vs. 0.3 pg/ml; P&lt;0.05) and IL-16 (182.7 vs. 85.2 pg/ml; P&lt;0.05) compared to controls. Primary myotube experiments revealed serum from trauma patients induced atrophy (32% decrease in diameter) compared to control serum-treated cells (P&lt;0.001).ConclusionSkeletal muscle from patients following acute trauma injury showed greater expression of atrophy and inflammatory markers. Trauma patient serum exhibited higher circulating pro-inflammatory cytokine concentrations. Primary human myotubes treated with serum from trauma patients showed significant atrophy compared to healthy serum-treated controls. We speculate a mechanism(s) acting via circulating factors may contribute to skeletal muscle pathology following acute trauma.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Activity of deep trunk muscles for postural control to predictable and unpredictable sagittal plane perturbations: Electromyographic analysis.

The activity of deep trunk muscles (psoas major; PM, quadratus lumborum; QL, transverse abdominis; TrA, and lumbar multifidus; MF) in response to external perturbation is not clearly known. This study aimed to record the onset and amount of activity of the deep trunk muscles during sagittal plane perturbations. Fourteen healthy males participated in this study. The activity of the right deep trunk muscles was recorded using wire electrodes. In standing, the participants performed three tasks: a pendulum impacted from anterior with predictable and unpredictable and posterior with unpredictable. In predictable anterior perturbation, the TrA and PM demonstrated feedforward activation, while all deep trunk muscles demonstrated feedback activation in unpredictable anterior and posterior perturbations. In the anticipatory postural adjustment phase, the activity of the TrA was large in predictable anterior perturbation, while that of all deep trunk muscles was slight in other perturbations. In the compensatory postural adjustment phase, the activity of the PM, QL, and TrA in unpredictable anterior perturbation and those of the PM, QL, and MF in unpredictable posterior perturbation were large. These results showed that the onset and magnitude of deep trunk muscle activity changed depending on both predictable or unpredictable perturbation and the direction of perturbation.

Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease. This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation. Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibres sampled from muscle biopsies. Using control's skeletal muscle fibers population, we classified each patient's fibers as having normal, low or high levels of CI and CIV and compared the proportions of fibers before and after exercise training. The significance of changes observed between pre- and post-exercise within patients was estimated using a permutation test. At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After resistance exercise training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Moreover, improvements in mitochondrial mass were correlated with the one-repetition maximum strength evaluation. Remarkably, 12-week resistance exercise training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting that the response to exercise is in part be due to changes in mitochondria.

A comparison between therapeutic effects of Salvia Officinalis. Extract, meloxicam and dexamethasone following acute sciatic nerve injury due to analgesic drug injection in rats

BackgroundAn intramuscular (IM) injection into gluteal muscle can lead to iatrogenic trauma to sciatic nerve. The drugs can be injected directly into sciatic or into the tissue adjacent to the nerve. Besides the direct damage to nerve due to needle and drug entrance to nerve tissue, the chemical nature of each drug activates immune system near healthy peripheral nerves in order to remove damaged tissues and start healing process. This immune system response has a great role in creating pathological pain and it makes functional recovery as a major challenge. Material methodIn this study, 25 adults male Fischer- Wistar rats were used. An analgesic drug (diclofenac) was injected in the muscles near sciatic nerve (4 groups) and also in sciatic nerve (1 group, nerve control group). For clinical assessment of sciatic nerves integrity, sciatic functional index test (SFI test) was done before, 1 day and 7 days after surgery. Treatments with meloxicam, dexamethasone and extract of Salvia Officinalis were started for 3 muscle groups and 1 group remained as a control muscle group. After 1 week, all the animals were euthanized under deep anesthesia and the sciatic nerves with surrounding muscles were removed and sent to histopathological examination. Resultsall three treatment groups showed decreased inflammatory process and increased repair regeneration in compare to control group. Although, the amount recovery in the dexamethasone group was significantly higher in compared to the control and other treatment groups. ConclusionThis study showed That IM injection of analgesic drug (Diclofenac), without direct damage to sciatic nerve, causes activation of the immune system and iatrogenic sciatic neuropathy. This study also showed therapeutic effects of two common drugs (NSAID and corticosteroids) and an extract of Salvia Officinalis. Treatment with all three drugs, decreased inflammatory response at injury site and increased recovery but Long-term usage of corticosteroids and NSAIDs can be challenging. The Salvia extract also have showed acceptable improvement effects with minimal side effects.

Nerve Transfer Surgery in Acute Flaccid Myelitis: Prognostic Factors, Long-Term Outcomes, Comparison With Natural History

BackgroundNerve transfer surgery is sometimes offered to patients with acute flaccid myelitis (AFM). The objectives of this study were to evaluate surgical efficacy, assess which clinical and neurophysiological data are valuable for preoperative planning, and report long-term outcomes. MethodsThis is a single-center, retrospective case series of patients with AFM who received nerve transfer surgery. All patients had preoperative electromyography and nerve conduction studies (EMG/NCS). Matched control muscles that did not receive nerve transfer surgery were defined in the same cohort. ResultsTen patients meeting inclusion criteria received a total of 23 nerve transfers (19 upper extremity, four lower extremity). The mean age at symptom onset was 3.8 years, surgery was 0.5 to 1.25 years after diagnosis, and mean follow-up was 2.3 years (range 1.3 to 4.5 years). Among muscles with preoperative strength Medical Research Council (MRC) grade 0, muscles receiving nerve transfers performed significantly better than those that did not (MRC grade 2.17 ± 0.42 vs 0 ± 0, respectively, P = 0.0001). Preoperative EMG/NCS predicted worse outcomes in recipient muscles with more abundant acute denervation potentials (P = 0.0098). Donor nerves found to be partially denervated performed equally well as unaffected nerves. Limited data suggested functional improvement accompanying strength recovery. ConclusionsNerve transfer surgery is an effective strategy to restore strength for patients with AFM with persistent, severe motor deficits. Postoperative outcomes in patients with complete paralysis are better than the natural history of disease. This study demonstrates the utility of preoperative clinical and electrophysiological data in guiding patient selection for nerve transfer surgery.

Predictors of static and dynamic balance control in kidney transplant recipients.

We aimed to evaluate balance control and lower extremity muscle strength in kidney transplant recipients (KTRs) including acomparison to ahealthy control group and determine the predictors of static and dynamic balance control after kidney transplantation. In this study 40 KTRs and 40healthy controls were included. Balance control was assessed using the Biodex balance system. The static postural stability test (SPST) and clinical test of sensory integration and balance (CTSIB) were used to assess static balance control whereas the dynamic postural stability test (DPST) and limits of stability test (LOST) were used for dynamic balance control. Lower extremity muscle strength was measured with ahand-held dynamometer. Renal functions and laboratory findings of KTRs were recorded. All the stability index scores of SPST and sway index in CTSIB were significantly higher in KTRs compared to healthy controls. The right anteroposterior stability index score in DPST and the reaction time in LOST were significantly higher whereas overall score in LOST and lower extremity muscle strength were significantly lower in KTRs. The linear regression analysis revealed that hemoglobin was the predictor of static balance control accounting for 11% of the variance and body weight was the predictor of dynamic balance control accounting for 34% of the variance. Balance control, both static and dynamic, are impaired in KTRs as well as lower extremity muscle strength. Hemoglobin level is apredictor of static balance control whereas body weight is apredictor of dynamic balance control after kidney transplantation.

Decreased Pyruvate but Not Fatty Acid Driven Mitochondrial Respiration in Skeletal Muscle of Growth Restricted Fetal Sheep.

Fetuses with intrauterine growth restriction (FGR) have impaired oxidative and energy metabolism, with persistent consequences on their postnatal development. In this study, we test the hypothesis that FGR skeletal muscle has lower mitochondrial respiration rate and alters the transcriptomic profiles associated with energy metabolism in an ovine model. At late gestation, mitochondrial oxygen consumption rates (OCRs) and transcriptome profiles were evaluated in the skeletal muscle collected from FGR and control fetuses. The ex vivo mitochondrial OCRs were reduced (p < 0.01) in permeabilized FGR soleus muscle compared to the control muscle but only with pyruvate as the metabolic substrate. Mitochondrial OCRs were similar between the FGR and control groups for palmitoyl-carnitine (fatty acid-driven) or pyruvate plus palmitoyl-carnitine metabolic substrates. A total of 2284 genes were differentially expressed in the semitendinosus muscle from growth restricted fetuses (false discovery rate (FDR) ≤ 0.05). A pathway analysis showed that the upregulated genes (FGR compared to control) were overrepresented for autophagy, HIF-1, AMPK, and FOXO signaling pathways (all with an FDR < 0.05). In addition, the expression of genes modulating pyruvate's entry into the TCA cycle was downregulated, whereas the genes encoding key fatty acid oxidation enzymes were upregulated in the FGR muscle. These findings show that FGR skeletal muscle had attenuated mitochondrial pyruvate oxidation, possibly associated with the inability of pyruvate to enter into the TCA cycle, and that fatty acid oxidation might compensate for the attenuated energy metabolism. The current study provided phenotypic and molecular evidence for adaptive deficiencies in FGR skeletal muscle.

Native lamin A/C proteomes and novel partners from heart and skeletal muscle in a mouse chronic inflammation model of human frailty.

Clinical frailty affects ∼10% of people over age 65 and is studied in a chronically inflamed (Interleukin-10 knockout; "IL10-KO") mouse model. Frailty phenotypes overlap the spectrum of diseases ("laminopathies") caused by mutations in LMNA. LMNA encodes nuclear intermediate filament proteins lamin A and lamin C ("lamin A/C"), important for tissue-specific signaling, metabolism and chromatin regulation. We hypothesized that wildtype lamin A/C associations with tissue-specific partners are perturbed by chronic inflammation, potentially contributing to dysfunction in frailty. To test this idea we immunoprecipitated native lamin A/C and associated proteins from skeletal muscle, hearts and brains of old (21-22months) IL10-KO versus control C57Bl/6 female mice, and labeled with Tandem Mass Tags for identification and quantitation by mass spectrometry. We identified 502 candidate lamin-binding proteins from skeletal muscle, and 340 from heart, including 62 proteins identified in both tissues. Candidates included frailty phenotype-relevant proteins Perm1 and Fam210a, and nuclear membrane protein Tmem38a, required for muscle-specific genome organization. These and most other candidates were unaffected by IL10-KO, but still important as potential lamin A/C-binding proteins in native heart or muscle. A subset of candidates (21 in skeletal muscle, 30 in heart) showed significantly different lamin A/C-association in an IL10-KO tissue (p < 0.05), including AldoA and Gins3 affected in heart, and Lmcd1 and Fabp4 affected in skeletal muscle. To screen for binding, eleven candidates plus prelamin A and emerin controls were arrayed as synthetic 20-mer peptides (7-residue stagger) and incubated with recombinant purified lamin A "tail" residues 385-646 under relatively stringent conditions. We detected strong lamin A binding to peptides solvent exposed in Lmcd1, AldoA, Perm1, and Tmem38a, and plausible binding to Csrp3 (muscle LIM protein). These results validated both proteomes as sources for native lamin A/C-binding proteins in heart and muscle, identified four candidate genes for Emery-Dreifuss muscular dystrophy (CSRP3, LMCD1, ALDOA, and PERM1), support a lamin A-interactive molecular role for Tmem38A, and supported the hypothesis that lamin A/C interactions with at least two partners (AldoA in heart, transcription factor Lmcd1 in muscle) are altered in the IL10-KO model of frailty.

Anesthesia Management via an Automated Control System for Propofol, Remifentanil, and Rocuronium Compared to Management by Anesthesiologists: An Investigator-Initiated Study.

We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.