Muscle Deficits Research Articles

"The Benefits of Physical Therapy in the Rehabilitation of Flat Feet in Autism Students between the ages of 10 and 14"

"Introduction: Autism is a syndrome, the causes of which are still being studied. All children are born with flexible flat feet and decrease in flatness with age, but it is not known how flat they should be with each increase in age. Methods: The research was carried out on 10 subjects, aged between 10-14 years, with autism and flat feet. In the rehabilitation program we used: massage of the lower limb, walking exercises, resistance exercises from the positions: supine, prone, sitting and standing, isometric contractions, varied walking and light running, exercises of relaxation combined with breathing exercises, cycling and athletic elements. Results: The results of the averages obtained at the two initial and final tests, an increase in the values at the final test can be observed, both in the left leg and in the right leg. The manual testing of the muscle strength registered averages between 86% - 94% at the initial testing and improved values at the final testing between 94% - 99%. Feiss line testing results show close means for both the left and right legs, and the standard deviation shows a spread of 0.66 at initial testing and 0.67 at final testing for the left leg and 0.55 and respectively 0.56 on the right leg. Discussion: Considering that studies show the connection between flat feet and overweight, the results of our study indicate that autistic students, despite having flat feet, are in the normal weight category. This aspect can be considered favorable in the approach of applied kinetic treatment. The problem of flat feet in subjects with intellectual deficiency is insufficiently studied; therefore our study could constitute an important landmark in this scientific approach. Conclusions: Analyzing the comparative results, it can be concluded that through physical therapy and the associated means, the muscle deficit can be recovered; the joint balance can be improved, reaching a correct posture while walking in autism flatfeet students"

PS-B10-11: PATHOPHYSIOLOGICAL STUDY OF COGNITIVE FRAILTY USING A MOUSE MODEL OF ALZHEIMER'S DISEASE

Objective: Hypertension is known to increase the risk of developing dementia including Alzheimer's disease (AD). The concept of cognitive frailty or motoric cognitive risk syndrome, representing a coexistence of physical and cognitive decline, has been attracting attention in the global aging society. However, the molecular mechanisms underlying the pathological interplay between these conditions remain largely unknown. Methods: We investigated the effects of AD pathogenesis on skeletal muscle by using APP23 mice, a mouse model of AD. Three-month-old male APP23 mice and wild-type mice from the same litter were evaluated for skeletal muscle function by grip strength, for cognitive function by passive avoidance and open field tests, and for glucose tolerance and 24-hour voluntary locomotion using a running wheel as factors related to both skeletal muscle function and cognitive function. After dissection, various organs, mainly skeletal muscle, were harvested and wet weight was evaluated. Results: Grip strength and some skeletal muscle weights of APP23 mice were lower than those of wild-type mice. The ipGTT was used to assess glucose tolerance, and the passive avoidance test and open field test were used to assess cognitive function, but there were no significant differences between genotypes. In the running wheel test, which measures voluntary locomotion, APP23 mice were significantly more active than wild-type mice suggesting that the muscle weakness in APP23 mice was not due to disuse. Conclusions: This study demonstrates that APP23 mice exhibit skeletal muscle deficits, including muscle weakness, along with cognitive dysfunction. In addition, APP23 mice showed behavioral abnormalities such as increased voluntary locomotion, which should contribute to increased skeletal muscle function, but skeletal muscle function was conversely decreased, suggesting that the effect of AD on skeletal muscle function is mediated by factors other than behavioral abnormalities due to cognitive dysfunction.

Peak Work Rate Increases With Lower Extremity-Focused Exercise Training in Adolescents With Fontan Circulation.

Background Skeletal muscle deficits are associated with worse exercise performance in the Fontan circulation and may be improved by exercise training. We aimed to assess the change in leg lean mass (a marker of skeletal muscle), exercise performance, and functional health status after a lower extremity-focused exercise intervention in adolescents with Fontan circulation. Methods and Results Densitometry for measurement of leg lean mass, cardiopulmonary exercise test, exercise cardiac magnetic resonance, peripheral vascular testing, physical activity questionnaire, and quality of life assessment were performed at baseline and after a 24-week, hybrid center- and home-based training program. Leg lean mass Z-scores were generated, and exercise parameters were expressed as percentage expected based on reference data. The effect of training was assessed by paired t-tests and simple linear regression. Twenty participants (15.6±1.7 years, 50% male) demonstrated low baseline leg lean mass Z-scores with no significant improvement with training (-1.38±1.02 pre versus -1.31±1.06 post, P=0.33). Maximum and percent predicted work increased from 121.9±29.8 (0.66±0.12) to 131.3±35.1 (0.70±0.15) watts (P=0.02). Peak respiratory exchange ratio increased (1.19±0.02 versus 1.25±0.01, P=0.02) but percent predicted oxygen consumption was unchanged, suggesting higher anaerobic activity after training. Physical activity questionnaire score positively associated with peak work at baseline (ß=18.13 [95% CI, 0.83-35.44], R2=0.21; P=0.04) but physical activity questionnaire, quality of life scores, exercise cardiac magnetic resonance performance, and peripheral vascular function were unchanged with training. Conclusions Peak work rate and anaerobic activity increased with lower extremity-focused training in adolescents with Fontan circulation. Larger studies should test the impact of these changes on functional status and quality of life.

Skeletal muscle deficits are associated with worse exercise performance in pediatric pulmonary hypertension.

BackgroundSkeletal muscle deficits are associated with worse exercise performance in adults with pulmonary hypertension (PH) but the impact is poorly understood in pediatric PH.ObjectiveTo study muscle deficits, physical inactivity, and performance on cardiopulmonary exercise test (CPET) and exercise cardiac magnetic resonance (eCMR) in pediatric PH.MethodsYouth 8–18 years participated in a prospective, cross-sectional study including densitometry (DXA) for measurement of leg lean mass Z-score (LLMZ), handheld dynamometer with generation of dominant and non-dominant handgrip Z-scores, Physical Activity Questionnaire (PAQ), CPET, and optional eCMR. CPET parameters were expressed relative to published reference values. CMR protocol included ventricular volumes and indexed systemic flow at rest and just after supine ergometer exercise. Relationships between LLMZ, PAQ score, and exercise performance were assessed by Pearson correlation and multiple linear regression.ResultsThere were 25 participants (13.7 ± 2.8 years, 56% female, 64% PH Group 1, 60% functional class I); 12 (48%) performed both CPET and eCMR. Mean LLMZ (–0.96 ± 1.14) was associated with PAQ score (r = 50, p = 0.01) and with peak oxygen consumption (VO2) (r = 0.74, p = < 0.001), VO2 at anaerobic threshold (r = 0.65, p < 0.001), and peak work rate (r = 0.64, p < 0.01). Higher handgrip Z-scores were associated with better CPET and eCMR performance. On regression analysis, LLMZ and PAQ score were positively associated with peak VO2, while handgrip Z-score and PAQ score were positively associated with peak work rate.ConclusionMuscle mass and strength are positively associated with exercise performance in pediatric PH. Future studies should determine the effect of rehabilitation programs on muscle properties and exercise performance.

Altered movement strategy during functional movement after an ACL injury, despite ACL reconstruction.

Knee joint functional deficits are common after anterior cruciate ligament (ACL) injury, but different assessment methods of joint function seem to provide contradicting information complicating recovery monitoring. We previously reported improved perceived knee function and functional performance (forward lunge ground contact time) in patients with an ACL injury from pre to 10 months post ACL reconstruction without improvement in knee-specific biomechanics. To further investigate this discrepancy, we additionally analyzed knee extensor and flexor muscle strength, and movement quality in the forward lunge (subjective and objective evaluations) and performed a full lower limb biomechanical analysis of the forward lunge movement. We included 12 patients with an ACL injury (tested before and after ACL reconstructive surgery) and 15 healthy controls from the previous study to the current investigation. Outcome measures were obtained pre and ~11 months post ACL reconstruction for the patients and at a single time point for the controls. Objective movement quality in the patients with an ACL injury showed an improvement from their pre reconstruction surgery visit to the post reconstruction visit but this was not observable in the subjective evaluation. Knee extensor muscle strength declined after the ACL reconstruction by 29% (p = 0.002) and both knee extensors (p < 0.001) and flexors (p = 0.027) were weaker in the patients post ACL reconstruction compared to healthy controls. ACL injured patients had an altered movement strategy in the forward lunge with reduced knee extensors contribution and increased hip extensor contribution compared to the controls both before and after the reconstruction. The altered movement strategy was associated with knee extensor muscle strength. This explorative study with a limited sample size found that clinicians should be aware that significant functional deficits in the knee extensor muscles, both in isolated muscle strength testing and during a functional movement, may be present although patients perceive an improvement in their knee function and present good functional performance without obvious movement quality issues.

Evaluation of symptomatic peripheral artery disease with media sclerosis using shear wave elastography of the lower limb muscle

Abstract Background Symptomatic peripheral artery disease (PAD) is challenging to diagnose in the presence of media sclerosis with incompressible arteries since standard ankle-brachial index (ABI) cannot be applied. Shear wave elastography (SWE) provides a novel ultrasound technique to measure muscle stiffness and to visualize muscle deficits at rest and during contraction. Furthermore, reduced muscle stiffness correlates with a possible hypoperfusion in the affected area. It is fast, non-invasive and associated with peripheral muscle weakness in chronic heart failure patients. Purpose SWE presents an important diagnostic tool for patients with PAD and concomitant media sclerosis. In this prospective observation study we evaluated the alterations of muscle stiffness (measured in kPa) at rest and during controlled activity. Methods Fifteen patients with peripheral artery disease and media sclerosis were included in this pilot study. Thirteen patients were symptomatic in different stages of PAD as a result of significant arterial stenosis/occlusions of the lower legs as assessed by oscillography and duplex sonography. ABI was invalid due to media sclerosis in all 15 patients. The examination was performed at rest and during contraction depicted by active dorsal flexion of the foot on both sides. The medial gastrocnemius muscle was used as a region of interest. Results Mean SWE measurements of medial gastrocnemius muscles showed significant muscle weakness at maximum exercise (103.4±25.9 kPa on the asymptomatic vs. 62.5±21.9 kPa in the symptomatic lower leg (p&amp;lt;0.001). Oscillography confirmed the SWE results by a decreased signal on the clinically symptomatic side. Conclusion SWE is suitable to detect muscle weakness during exercise in the symptomatic leg of mediasclerotic PAD patients. Since ABI measurements are usually invalid these patients with media sclerosis, shear wave elastography of lower limb muscles may contribute for a non-invasive diagnosis of symptomatic PAD. Larger randomized clinical trials are necessary to confirm our results. Funding Acknowledgement Type of funding sources: None.

Possible association of high-density lipoprotein cholesterol levels with trunk muscle deficits and decrease in energy expenditure in patients with or at risk for COPD: A pilot study.

Chronic obstructive pulmonary disease (COPD) is associated with low muscle mass and function caused by malnutrition and physical inactivity. We aimed to investigate possible associations between serum biomarkers and clinical traits including computed tomography-derived muscle measurements and energy expenditure indices in COPD. Total energy expenditure (TEE) was measured by the doubly labeled water method, while physical activity level (PAL) was calculated as TEE/basal metabolic rate. Cross-sections and densities of pectoralis, rectus abdominis, and erector spinae muscles were measured. Serum biomarkers included adiponectin, insulin-like growth factor-1, and high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol (C). HDL-C levels were significantly correlated with all muscle areas, densities, and TEE. Only LDL-C levels were correlated with PAL. HDL-C level was a potential biomarker for trunk muscle volumes and functions, as well as total energy expenditure in COPD.

Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.

Nemaline myopathy (NM) is characterized by skeletal muscle weakness and atrophy. No curative treatments exist for this debilitating disease. NM is caused by mutations in proteins involved in thin-filament function, turnover, and maintenance. Mutations in nebulin, encoded by NEB, are the most common cause. Skeletal muscle atrophy is tightly linked to upregulation of MuRF1, an E3 ligase, that targets proteins for proteasome degradation. Here, we report a large increase in MuRF1 protein levels in both patients with nebulin-based NM, also named NEM2, and in mouse models of the disease. We hypothesized that knocking out MuRF1 in animal models of NM with muscle atrophy would ameliorate the muscle deficits. To test this, we crossed MuRF1 KO mice with two NEM2 mouse models, one with the typical form and the other with the severe form. The crosses were viable, and muscles were studied in mice at 3 months of life. Ultrastructural examination of gastrocnemius muscle lacking MuRF1 and with severe NM revealed a small increase in vacuoles, but no significant change in the myofibrillar fractional area. MuRF1 deficiency led to increased weights of various muscle types in the NM models. However, this increase in muscle size was not associated with increased in vivo or in vitro force production. We conclude that knocking out MuRF1 in NEM2 mice increases muscle size, but does not improve muscle function.

Intra-articular botulinum toxin A injection for painful base-of-thumb osteoarthritis: a double-blind, randomised, controlled, phase 3 trial (RHIBOT).

Intra-articular botulinum toxin A injection might have analgesic effects in patients with joint diseases. We aimed to compare the effects of intra-articular botulinum toxin A injection with those of intra-articular saline injection for patients with painful base-of-thumb osteoarthritis. RHIBOT was a double-blind, randomised, controlled, phase 3 trial conducted at Cochin Hospital, Paris, France. We recruited adult patients with x-ray evidence of trapeziometacarpal osteoarthritis who fulfilled the 1990 American College of Rheumatology criteria for hand osteoarthritis and reported a pain intensity score of at least 30 on an 11-point numeric rating scale (0: no pain to 100: maximal pain). Participants were randomly assigned (1:1), using a computer-generated randomisation list with permuted blocks of variable size (4 or 6), to receive an ultrasound-guided injection of either botulinum toxin A (50 Allergan units) in 1 mL of saline (experimental group) or 1 mL of saline alone (control group) in the trapeziometacarpal joint, in addition to custom-made rigid splinting. The primary outcome was the mean change from baseline in base-of-thumb pain in the previous 48 h on a numeric rating scale at 3 months after injection, analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT03187626. Between Nov 2, 2018, and Nov 3, 2020, we assessed 370 individuals for eligibility and recruited 60 (16%) participants (mean age 64·9 years [SD 9·4], 47 [78%] women and 13 [22%] men), of whom 30 (50%) participants were randomly assigned to the experimental group and 30 (50%) to the control group. At baseline, base-of-thumb pain score was 60·0 of 100·0 (SD 15·9). At 3 months, the mean reduction in base-of-thumb pain was -25·7 (95% CI -35·5 to -15·8) in the experimental group and -9·7 (-17·1 to -2·2) in the control group (absolute difference -16·0 [-28·1 to -3·9]; p=0·043). Overall, 51 adverse events were reported in both groups: 27 (53%) in the experimental group and 24 (47%) in the control group. During follow-up, 14 (47%) participants in the experimental group and two (7%) participants in the control group reported mild transient motor deficit of the thenar muscle. No serious adverse events were reported. Botulinum toxin A could be considered as a fast-acting, intra-articular therapy targeting chronic pain in individuals with base-of-thumb osteoarthritis. Future studies are needed to investigate the potential mechanism of the effects observed in this trial, to replicate our findings, and to assess the effects of repeated injections over time and their clinical effectiveness, including an analysis of cost-effectiveness. Assistance Publique-Hôpitaux de Paris.

Test-Retest Reliability of Repetitive Ocular Vestibular Evoked Myogenic Potentials in Myasthenia Gravis Patients and Healthy Control Subjects.

Repetitive ocular vestibular evoked myogenic potentials (ROVEMP) are a novel diagnostic test to quantify neuromuscular transmission deficits in extraocular muscles in myasthenia gravis. We aimed to investigate the test-retest reliability of the ROVEMP and the effect of amplitude and age. We performed the ROVEMP test twice in 19 patients with myasthenia gravis (52.7 ± 19.8 years) and in 15 healthy control subjects (46.5 ± 16 years). The Bland-Altman level of agreement was determined. The relationship between test-retest reliability and signal quality, participant age and signal amplitude was studied. Limits of agreement were from -179.9 to 139.3 in myasthenia gravis patients and from -56.9 to 89.5 in healthy control subjects. Difference between measurements correlated with signal amplitude ( r = -0.50, P < 0.001). Combining the primary cohort with previously published data from 114 subjects, we found a significant negative correlation between age and reference amplitude ( r = -0.163, P = 0.045). This study shows that in our hands, the test-retest reliability of the ROVEMP is not optimal. Measurements with higher reference amplitude had a better quality, higher reproducibility, and increased diagnostic yield. We caution against the use of ROVEMP measurements of lower amplitude in clinical practice. In addition, given the correlation between age and amplitude, age matching of healthy control subjects and patients is essential in future studies.

How Well Do Low Population-Specific Values for Muscle Parameters Associate with Indices of Poor Physical Health? Cross-Sectional Data from the Geelong Osteoporosis Study.

We aimed to examine associations between skeletal muscle deficits and indices of poor health. Cut-points for skeletal muscle deficits were derived using data from the Geelong Osteoporosis Study and definitions from the revised European Consensus on Definition and Diagnosis and the Foundation for the National Institutes of Health. Participants (n = 665; 323 women) aged 60–96 year had handgrip strength measured by dynamometry and appendicular lean mass by whole-body dual-energy X-ray absorptiometry. Physical performance was assessed using the Timed Up and Go test. Sex-specific cut-points were equivalent to two standard deviations below the mean young reference range from the Geelong Osteoporosis Study. Indices of poor health included fractures, falls, and hospitalisations. Low trauma fractures since age 50 year (excluding skull, face, digits) were self-reported and confirmed using radiological reports. Falls (≥1 in the past 12 months) and hospitalisations (past month) were self-reported. Logistic regression models (age- and sex-adjusted) were used to examine associations. Receiver Operating Characteristic curves were applied to determine optimal cut-points for handgrip strength, Timed Up and Go, appendicular lean mass/height2, and appendicular lean mass/body mass index that discriminated poor health outcomes. There were 48 participants (6.9%) with hospitalisations, 94 (13.4%) with fractures, and 177 (25.3%) with at least one fall (≥1). For all cut-points, low handgrip strength was consistently associated with falls. There was little evidence to support an association between low appendicular lean mass, using any cut-point, and indices of poor health. Optimal cut-offs for predicting falls (≥1) were: handgrip strength 17.5 kg for women and 33.5 kg for men; Timed Up and Go 8.6 s for women and 9.9 s for men; appendicular lean mass/height2 6.2 kg/m2 for women and 7.46 kg/m2 for men; and appendicular lean mass/body mass index 0.6 m2 for women and 0.9 m2 for men. In conclusion, muscle strength and function performed better than lean mass to indicate poor health. These findings add to the growing evidence base to inform decisions regarding the selection of skeletal muscle parameters and their optimal cut-points for identifying sarcopenia.

Implications of lower extremity muscle power and force for walking and fatigability in multiple sclerosis – An exploratory pilot-study

BackgroundLimitations in physical function are common in Multiple Sclerosis (MS), yet it is neither clear how muscle power implicates physical function and walking-fatigability. This pilot-study aims to investigate (1) deficits in muscle power/force alongside walking in persons with MS; (2) associations between muscle power/force and physical functions and (3) the impact of prolonged walking in muscle power/force. Methods30 relapse-remitting persons with MS and 28 healthy controls performed chair rise and plantar flexion on a force platform before and after 12-minutes of intermittent walking to measure lower extremity muscle power/force. GaitRite measured walking speed. The percentage change in distance walked was also calculated. Persons with MS were classified into subgroups according to walking-fatigability and mobility disability status (Patient Determined Disease Steps). FindingsHigher deficits in muscle power compared to force were observed in persons with MS vs. healthy controls particularly in persons with MS having higher disability. Muscle power and force were associated with walking capacity, mobility disability and subjective fatigue, but not with percentage change in distance walked. Persons with MS slowed down over the course of the 12-min intermittent walking, whereas decrements in walking speed and muscle power/force (derived from chair rise) were observed in persons with MS presenting walking-fatigability only. InterpretationMuscle power and force are impaired in persons with MS and appear to be critical for physical function in MS. This exploratory pilot study further suggests that muscle power/force from chair rise could contributes to walking-fatigability which therefore offer future treatment targets.

Strength, Flexibility and Postural Control of the Trunk and Lower Body in Participants with and without Patellofemoral Pain

Patellofemoral pain (PFP) is a frequent knee condition. The aim of this study was to investigate strength, flexibility and postural control in people with and without PFP. Fifty-five participants between 14 and 54 years of age (PFP = 18, control group = 37) were included. Strength and flexibility for all trunk, hip, knee and ankle muscle groups were measured along with postural control outcomes. Analyses were conducted based on the “affected” and “non-affected” leg within-group and between-groups. Between-groups analysis demonstrated a statistically lower strength of trunk muscles (range: 35.8–29.3%, p &lt; 0.001), knee extensors (20.8%, p = 0.005) and knee flexors (17.4%, p = 0.020) in PFP participants. Within-group analysis proved an 8.7% (p = 0.018) greater hip internal rotation strength and ankle extension flexibility (p = 0.032) of the “affected side” in PFP participants. This was, to our knowledge, the first study to investigate the strength of all trunk muscle groups. The results indicate that participants with PFP exhibit impaired strength of trunk muscle groups, along with knee muscle deficits, which may present a rehabilitation target. Clinicians should consider implementing trunk strengthening exercises into PFP programs along with knee-targeting exercise programs.

Hip Abductor Strength Asymmetry: Relationship to Upper Extremity Injury in Professional Baseball Players.

Hip strength is an important factor for control of the lumbo-pelvic-hip complex. Deficits in hip strength may affect throwing performance and contribute to upper extremity injuries. Deficits in hip abduction isometric strength would be greater in those who sustained an upper extremity injury and hip strength would predict injury incidence. Prospective cohort study. Level 3. Minor League baseball players (n = 188, age = 21.5 ± 2.2 years; n = 98 pitchers; n = 90 position players) volunteered. Hip abduction isometric strength was assessed bilaterally with a handheld dynamometer in side-lying position, expressed as torque using leg length (N·m). Hip abduction strength asymmetry was represented by [(trail leg/lead leg) × 100]. Overuse or nontraumatic throwing arm injuries were prospectively tracked. Poisson regression models were used to estimate relative risk ratios associated with hip asymmetry; confounders, including history of prior overuse injury in the past year, were included. Hip abduction asymmetry ranged from 0.05% to 57.5%. During the first 2 months of the season, 18 players (n = 12 pitchers) sustained an upper extremity injury. In pitchers, for every 5% increase in hip abduction asymmetry, there was a 1.24 increased risk of sustaining a shoulder or elbow injury. No relationship between hip abduction strength and injury was observed for position players. Hip abduction asymmetry in pitchers was related to subsequent upper extremity injuries. The observed risk ratio indicates that hip abduction asymmetry may contribute a significant but small increased risk of injury. Hip abduction muscle deficits may affect pitching mechanics and increase arm stress. Addressing hip asymmetry deficits that exceed 5% may be beneficial in reducing upper extremity injury rates in pitchers.

Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations.

LGMDR1 is caused by mutations in the CAPN3 gene that encodes calpain 3 (CAPN3), a non-lysosomal cysteine protease necessary for proper muscle function. Our previous findings show that CAPN3 deficiency leads to reduced SERCA levels through increased protein degradation. This work investigates the potential contribution of the ubiquitin-proteasome pathway to increased SERCA degradation in LGMDR1. Consistent with our previous results, we observed that CAPN3-deficient human myotubes exhibit reduced SERCA protein levels and high cytosolic calcium concentration. Treatment with the proteasome inhibitor bortezomib (Velcade) increased SERCA2 protein levels and normalized intracellular calcium levels in CAPN3-deficient myotubes. Moreover, bortezomib was able to recover mutated CAPN3 protein in a patient carrying R289W and R546L missense mutations. We found that CAPN3 knockout mice (C3KO) presented SERCA deficits in skeletal muscle in the early stages of the disease, prior to the manifestation of muscle deficits. However, treatment with bortezomib (0.8 mg/kg every 72 h) for 3 weeks did not rescue SERCA levels. No change in muscle proteasome activity was observed in bortezomib-treated animals, suggesting that higher bortezomib doses are needed to rescue SERCA levels in this model. Overall, our results lay the foundation for exploring inhibition of the ubiquitin-proteasome as a new therapeutic target to treat LGMDR1 patients. Moreover, patients carrying missense mutations in CAPN3 and presumably other genes may benefit from proteasome inhibition by rescuing mutant protein levels. Further studies in suitable models will be necessary to demonstrate the therapeutic efficacy of proteasome inhibition for different missense mutations.

Development of a Rat Model of Fasciotomy Treatment for Compartment Syndrome.

Skeletal muscle injuries are a major cause of disability for military and civilian populations. Compartment syndrome (CS) in skeletal muscle results from an edema-induced increase in intracompartmental pressure (ICP) after primary injury. Untreated ICP will occlude the tissue vasculature, tissue necrosis, and potential loss of limb. The current standard of care for CS is surgical fasciotomy, an incision through the muscle fascia to relieve ICP. Early fasciotomy will preserve the limb, but often leaves patients with long-term scarring and reduced muscle function. Our group previously developed and characterized a rat model of CS to explore the pathophysiology of CS and test new therapies. We present an expansion of this CS model, including the fasciotomy, to better simulate clinical treatment. CS was induced on the hind limb of adult male Lewis rats and fasciotomy was performed 24 h later. Less than 20% of the rats that underwent fasciotomy showed detectable force 4 days after injury, compared with the 75% of rats that underwent CS induction without fasciotomy. Muscles undergoing fasciotomy showed a significant increase in fibrosis and an increased number of macrophages, Pax7+ satellite cells, and α-smooth muscle actin+ myofibroblasts at 7 days postinjury. These data indicate that the use of fasciotomy in a rat model of CS resulted in injury sequelae that reflect the severity of human clinical disease presentation along with current standard of care. Impact Statement Current animal models of skeletal muscle injury struggle to accurately reflect the injury sequelae seen in humans, particularly in rats and mice. These animals also recover faster than humans do. More accurate recapitulation of the injury is needed to better study the injury progression, as well as screen for novel therapies. This research combines an existing model of compartment syndrome with its clinical standard of care (fasciotomy), creating a more accurate rat model of injury, and providing for a better treatment screening tool. These results show how our model leads to a sustained skeletal muscle deficit with increased inflammation.

Diet, Muscle Protein Synthesis and Autophagy Relationships in Cancer: An Attempt to Understand Where Are We Going, and Why

Protein-based structures are indispensable to maintain life, so identification and removal of worn out structures achieved through proteostasis, the sum of micro and macro-autophagy (autophagy) plus ubiquitin-proteasome system, must balance renewal by new synthesis. Many of the elements controlling dynamically equilibria between protein synthesis and protein degradation have been identified and modalities of activation actively studied, still we are quite far from mastering how this balance is ruled. Failure to maintain a positive balance between protein synthesis and protein degradation would result in sarcopenia, defined as the loss of skeletal muscle mass and function, a major clinical problem frequently accompanying chronic illnesses, but peculiarly spotted in cancer and in elderly patients. Also, how cancer is fed, and how nutrition in cancer patients may affect evolution and therapy effectiveness is another field of opinions and uncertainty. On the other hand, exercise and nutrition tailored to provide adequate amounts of amino acids are widely considered a necessary strategy for prevention and treatment of protein synthetic deficits in muscles. This paper will synthetically review how different nutritional strategies and energy production may interconnect efficiently synthesis and scavenging of aged and overused protein molecules by autophagy. Finally, since energy availability rules life and death of cells and organisms, an hypothesis predicting how energy may control the ratios among protein synthesis and autophagy is proposed: in normal conditions, protein syntheses have a key role in autophagy activation by consuming large amounts of energy when forming peptidic bonds, that is adenosine tri-phosphate (ATP) is consumed to mono-phospahate (AMP), thus decreasing ATP to AMP ratios. Conversely, both protein syntheses and autophagy may be scarcely activated when low availability of ATP would result also in lowest concentrations of AMP. In this peculiar setting, reduced rates of both protein syntheses and autophagy would be observed, resulting in worsening of protein balance and functions.

Isokinetic exercises in quadriceps strength and endurance recovery after anterior cruciate ligament reconstruction

Background/Aim: Muscle strength and endurance recovery of the quadriceps after anterior cruciate ligament reconstruction is necessary for normal knee function. In addition to the use of the isokinetic dynamometer for diagnostic purposes, its possible therapeutic effect is also important, ie targeted correction of the measured muscle deficit. This work was aimed to examine the level of quadriceps strength and endurance recovery 6 months after the anterior cruciate ligament reconstruction in patients who performed isokinetic training and to determine whether it is a superior therapeutic intervention compared to isodynamic training. Methods: A total of 70 patients of both sexes were monitored in a prospective clinical study. Three months postoperatively, all patients had quadriceps torque measured to body weight on an isokinetic dynamometer at angular speeds of 60 and 180 °/s. Patients were divided into two groups according to the type of applied rehabilitation protocol. Group A patients (n = 35) underwent a rehabilitation program 5 times a week using an individual kinesitherapy program (isometric and isotonic exercises for quadriceps and hamstrings) and neuromuscular electrostimulation of the quadriceps. In addition patients from group B (n = 35) were included in targeted isokinetic exercises for the quadriceps. Control isokinetic testing was performed 6 months after surgery. The comparison of the effect of the applied therapeutic procedures in groups A and B was performed with the Student t-test (p &lt; 0.05). Results: An average age of patients was 27.29 ± 5.94 years. In patients in group B, statistically significantly higher values of the peak torque to body weight were measured at angular velocities of 60 and 180 °/s for the quadriceps of the operated knee 6 months after reconstruction of the anterior cruciate ligament with hamstring tendons (p &lt; 0.05). Conclusion: Isokinetic training achieved significantly better quadriceps strength and endurance in patients 6 months after anterior cruciate ligament reconstruction with hamstring tendons compared to dynamic exercises.

Adolescent Athletes Demonstrate Inferior Objective Profiles at the Time of Return to Sport After ACLR Compared With Healthy Controls.

Background:Athletes display persistent muscle deficits and altered limb-loading mechanics at the time of return to sport (RTS) after anterior cruciate ligament reconstruction (ACLR).Purpose:To compare an objective profile of adolescent athletes at RTS after ACLR to matched healthy controls.Study Design:Cross-sectional study; Level of evidence, 3.Methods:Included were 124 participants; 62 patients who underwent ACLR (15.4 ± 1.7 years) and 62 healthy controls (15.3 ± 1.7 years). Motion capture and force plates were used to capture joint motions during jump landing (JL) and single-limb squat (SLS) tasks. Energy absorption contribution (EAC) was calculated, and repeated-measures analysis of variance was used to assess for EAC differences between groups. Participants completed an International Knee Documentation Committee (IKDC) Subjective Knee Form, and isokinetic quadriceps and hamstring strength testing was performed on each limb. Independent t tests were run to examine age, height, weight, and IKDC scores as well as compare differences between groups for quadriceps and hamstring strength.Results:A significant group × joint interaction was found for JL (P < .001) and SLS (P < .001). For JL, patients who underwent ACLR utilized significantly greater hip (P < .001) and significantly less knee (P < .001) EAC on the surgical limb compared with controls. During SLS, patients who underwent ACLR utilized significantly greater hip (P < .001) and significantly less knee (P < .001) EAC on the surgical limb compared with controls. The ACLR cohort demonstrated lower IKDC scores (P < .001) and significantly lower quadriceps strength on the surgical limb (P < .001) than controls. There were no differences in surgical limb hamstring strength between the ACLR cohort and healthy controls (P = .701).Conclusion:Compared with matched healthy controls, the participants who underwent ACLR in this study demonstrated an inferior objective profile at RTS, consisting of deficits in surgical limb loading, self-reported outcomes, and strength.

CLINICAL OUTCOMES OF TORQUE DEFICIT REDUCTION IN KNEE EXTENSORS AND FLEXORS AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION

In this prospective study, we presented the effect of isokinetic training on the clinical outcome of rehabilitation in relation to the reduction of the torque deficit in thigh muscles (DEF) after anterior cruciate ligament (LCA) reconstruction. The prospective study followed 144 subjects, 72 women and 72 men, with a mean age of 28.20 ± 4.52, four months after anterior cruciate ligament reconstruction with a hamstring graft. Subjects were divided into two groups according to the type of rehabilitation treatment they underwent. Subjects of the isokinetic group (72 subjects, 36 males and 36 females), underwent kinesitherapy according to the isokinetic exercise protocol which consisted of a one-day isokinetic training lasting for thirty minutes, five times a week for six weeks. Subjects of the classical group (72 subjects, 36 males and 36 females) underwent kinesitherapy based on standard isotonic exercises to increase muscle strength, i.e. exercises with weights and in the gym. The difference in the outcome of rehabilitation was objectified by a concentric-concentric isokinetic test at an angular velocity of 60 °/s before the start, after three weeks and after six weeks of rehabilitation. The monitoring parameters were: torque deficit of the injured leg knee extensor in relation to the uninjured leg (EXDEF) -% and torque deficit of the knee flexor of the injured leg in relation to the uninjured leg (FLDEF) -%.