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The intrinsic force production capability of human muscle can be expressed as "Specific Tension," or, the maximum force generated per cross-sectional area of muscle fibers. This value can be used to determine, for example, whether muscle quality changes during exercise, atrophy, disease, or hypertrophy. A value of 22.5 N/cm2 for mammalian muscle has generally become accepted based on detailed studies of small mammals. Determining the specific tension of human muscle is much more challenging since almost all determinations are indirect. Calculation of human muscle specific tension requires an understanding of that muscle's contribution to joint torque, its activation magnitude, tendon compliance, and joint moment arm. Determining any of these parameters is technically challenging in humans and thus, it is no surprise that human specific tension values reported vary from 2 to 73 N/cm2. In this systematic review, we screened 1,506 published papers and identified 29 studies published between 1983 and 2023 that used appropriate methods and which reported 95 human specific tension values. We have weighted each parameter based on whether it was directly measured, estimated, or calculated based on the literature, with decreasing weighting used for the more indirect methods. Based on this exhaustive review of the relevant human literature, we suggest that the most accurate value that should be used for human muscle specific tension is 26.8 N/cm2.

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Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating preclinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of nonspecific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, to investigate cachexia-related function at the basic science level. Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC)-derived cells. One hundred twenty-eight animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. We extended the survival of the KPC orthotopic model to 8-9 wk postimplantation using a relatively low 100-cell dose of DT10022 KPC cells (P < 0.001). In this low-dose orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 wk postimplantation compared with controls (P < 0.001). Gait speed in LO animals declined as early as 2 wk postimplantation, whereas grip strength change was a late event. Principal component and regression analyses revealed distinct cachectic and noncachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (P < 0.01), whereas grip strength decline was not (P = 0.19). Gait speed represents an accurate surrogate for cachexia-related physical function as opposed to grip strength.NEW & NOTEWORTHY Previous studies of cancer-induced cachexia have been confounded by the relatively rapid death of animal subjects. Using a lower dose of cancer cells in combination with a battery of behavioral, structural, histological, and biochemical techniques, we show that gait speed is actually the best indicator of functional decline due to cachexia. Future studies are required to define the underlying physiological basis of these findings.

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The circadian clock orchestrates vital physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day. This study identifies an intricate interplay between the circadian clock within muscle stem cells (SCs) and their capacity to modulate the immune microenvironment during muscle regeneration. We uncover that the SC clock provokes time of day-dependent induction of inflammatory response genes following injury, particularly those related to neutrophil activity and chemotaxis. These responses are driven by rhythms of cytosolic regeneration of the signaling metabolite NAD+. We demonstrate that genetically enhancing cytosolic NAD+ regeneration in SCs is sufficient to induce robust inflammatory responses that significantly influence muscle regeneration. Furthermore, using mononuclear single-cell sequencing of the regenerating muscle niche, we uncover a key role for the cytokine CCL2 in mediating SC-neutrophil crosstalk in a time of day-dependent manner. Our findings highlight a crucial intersection between SC metabolic shifts and immune responses within the muscle microenvironment, dictated by the circadian rhythms, and underscore the potential for targeting circadian and metabolic pathways to enhance tissue regeneration.

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BACKGROUND: After stroke, restoring safe, independent, and efficient walking is a top rehabilitation priority. However, in nearly 70% of stroke survivors asymmetrical walking patterns and reduced walking speed persist. This case series study aims to investigate the effectiveness of transcutaneous spinal cord stimulation (tSCS) in enhancing walking ability of persons with chronic stroke. METHODS: Eight participants with hemiparesis after a single, chronic stroke were enrolled. Each participant was assigned to either the Stim group (N = 4, gait training + tSCS) or Control group (N = 4, gait training alone). Each participant in the Stim group was matched to a participant in the Control group based on age, time since stroke, and self-selected gait speed. For the Stim group, tSCS was delivered during gait training via electrodes placed on the skin between the spinous processes of C5-C6, T11-T12, and L1-L2. Both groups received 24 sessions of gait training over 8 weeks with a physical therapist providing verbal cueing for improved gait symmetry. Gait speed (measured from 10 m walk test), endurance (measured from 6 min walk test), spatiotemporal gait symmetries (step length and swing time), as well as the neurophysiological outcomes (muscle synergy, resting motor thresholds via spinal motor evoked responses) were collected without tSCS at baseline, completion, and 3 month follow-up. RESULTS: All four Stim participants sustained spatiotemporal symmetry improvements at the 3 month follow-up (step length: 17.7%, swing time: 10.1%) compared to the Control group (step length: 1.1%, swing time 3.6%). Additionally, 3 of 4 Stim participants showed increased number of muscle synergies and/or lowered resting motor thresholds compared to the Control group. CONCLUSIONS: This study provides promising preliminary evidence that using tSCS as a therapeutic catalyst to gait training may increase the efficacy of gait rehabilitation in individuals with chronic stroke. Trial registration NCT03714282 (clinicaltrials.gov), registration date: 2018-10-18.

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Muscle isometric torque fluctuates according to time-of-day with such variation owed to the influence of circadian molecular clock genes. Satellite cells (SCs), the muscle stem cell population, also express molecular clock genes with several contractile-related genes oscillating in a diurnal pattern. Currently, limited evidence exists regarding the relationship between SCs and contractility, although long-term SC ablation alters muscle contractile function. Whether there are acute alterations in contractility following SC ablation and with respect to the time-of-day is unknown. We investigated whether short-term SC ablation affected contractile function at two times of day and whether any such alterations led to different extents of eccentric contraction-induced injury. Using an established mouse model to deplete SCs, we characterized muscle clock gene expression and ex vivo contractility at two times-of-day (morning: 0700 and afternoon: 1500). Morning-SC+ animals demonstrated ∼25%-30% reductions in tetanic/eccentric specific forces and, after eccentric injury, exhibited ∼30% less force-loss and ∼50% less dystrophinnegative fibers versus SC- counterparts; no differences were noted between Afternoon groups (Morning-SC+: -5.63 ± 0.61, Morning-SC-: -7.93 ± 0.61; N/cm2; P < 0.05) (Morning-SC+: 32 ± 2.1, Morning-SC-: 64 ± 10.2; dystrophinnegative fibers; P < 0.05). As Ca++ kinetics underpin force generation, we also evaluated caffeine-induced contracture force as an indirect marker of Ca++ availability and found similar force reductions in Morning-SC+ vs. SC- mice. We conclude that force production is reduced in the presence of SCs in the morning but not in the afternoon, suggesting that SCs may have a time-of-day influence over contractile function.NEW & NOTEWORTHY Muscle isometric torque fluctuates according to time-of-day with such variation owed to molecular clock regulation. Satellite cells (SCs) have recently demonstrated diurnal characteristics related to muscle physiology. In our work, force production was reduced in the presence versus absence of SCs in the morning but, not in the afternoon. Morning-SC+ animals, producing lower force, sustained lesser degrees of injury versus SC- counterparts. One potential mechanism underpinning lower forces produced appears to be lower calcium availability.

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Modern approaches to discovering molecular mechanisms and validating treatments for age-related neuromusculoskeletal dysfunction typically rely on high-throughput transcriptome analysis. Previously harvested and fixed tissues offer an incredible reservoir of untapped molecular information. However, obtaining RNA from such formaldehyde-fixed neuromusculoskeletal tissues, especially fibrotic aged tissues, is technically challenging and often results in RNA degradation, chemical modification and yield reduction, prohibiting further analysis. Therefore, we developed a protocol to extract high-quality RNA from formaldehyde-fixed brain, cartilage, muscle and peripheral nerve isolated from naturally aged mice. Isolated RNA produced reliable gene expression data comparable to fresh and flash-frozen tissues and was sensitive enough to detect age-related changes, making our protocol valuable to researchers in the field of aging.

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A skeletal muscle's peak force production and excursion are based on its architectural properties that are, in turn, determined by its mass, muscle fiber length and physiological cross-sectional area (PCSA). In the classic interspecific study of mammalian muscle scaling, it was demonstrated that muscle mass scales positively allometrically with body mass whereas fiber length scales isometrically with body mass, indicating that larger mammals have stronger leg muscles than they would if they were geometrically similar to smaller ones. Although this relationship is highly significant across species, there has never been a detailed intraspecific architectural scaling study. We have thus created a large dataset of 896 muscles across 34 human lower extremities (18 females and 16 males) with a size range including approximately 90% and 70% of the United States population height and mass, respectively, across the range 36-103 years. Our purpose was to quantify the scaling relationships between human muscle architectural properties and body size. We found that human muscles depart greatly from isometric scaling because muscle mass scales with body mass1.3 (larger exponent than isometric scaling of 1.0) and muscle fiber length scales with negative allometry with body mass0.1 (smaller exponent than isometric scaling of 0.33). Based on the known relationship between architecture and function, these results suggest that human muscles place a premium on muscle force production (mass and PCSA) at the expense of muscle excursion (fiber length) with increasing body size, which has implications for understanding human muscle design as well as biomechanical modeling.

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Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating "avatars" (herein defined as an extension of "digital twins") of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

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Central and peripheral nervous system lesions may disrupt the intricate balance of the prime movers of the wrist. In spasticity, hyperactive wrist flexors create a flexion moment and, if untreated, can lead to flexion contractures. In patients with C6 spinal cord injury and tetraplegia, the posterior interosseus nerve is typically affected by a complex pattern of upper and/or lower motoneuron lesions causing radial deviation of the wrist due to loss of ulnar deviation actuators. In this report, we illustrate severe pathomechanics that may occur even with relatively modest changes in wrist balance. These results illustrate how thorough understanding of muscle-tendon-joint interaction aids in designing tendon and nerve reconstructive surgeries to normalize wrist positions and balance in neuromuscular conditions.

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OBJECTIVE: Inpatient rehabilitation represents a critical setting for stroke treatment, providing intensive, targeted therapy and task-specific practice to minimize a patient's functional deficits and facilitate their reintegration into the community. However, impairment and recovery vary greatly after stroke, making it difficult to predict a patient's future outcomes or response to treatment. In this study, the authors examined the value of early-stage wearable sensor data to predict 3 functional outcomes (ambulation, independence, and risk of falling) at rehabilitation discharge. METHODS: Fifty-five individuals undergoing inpatient stroke rehabilitation participated in this study. Supervised machine learning classifiers were retrospectively trained to predict discharge outcomes using data collected at hospital admission, including patient information, functional assessment scores, and inertial sensor data from the lower limbs during gait and/or balance tasks. Model performance was compared across different data combinations and was benchmarked against a traditional model trained without sensor data. RESULTS: For patients who were ambulatory at admission, sensor data improved the predictions of ambulation and risk of falling (with weighted F1 scores increasing by 19.6% and 23.4%, respectively) and maintained similar performance for predictions of independence, compared to a benchmark model without sensor data. The best-performing sensor-based models predicted discharge ambulation (community vs household), independence (high vs low), and risk of falling (normal vs high) with accuracies of 84.4%, 68.8%, and 65.9%, respectively. Most misclassifications occurred with admission or discharge scores near the classification boundary. For patients who were nonambulatory at admission, sensor data recorded during simple balance tasks did not offer predictive value over the benchmark models. CONCLUSION: These findings support the continued investigation of wearable sensors as an accessible, easy-to-use tool to predict the functional recovery after stroke. IMPACT: Accurate, early prediction of poststroke rehabilitation outcomes from wearable sensors would improve our ability to deliver personalized, effective care and discharge planning in the inpatient setting and beyond.

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ABSTRACT: Developing a culture of innovative thinking and one that emphasizes clinician-researcher interaction is critical for the future of rehabilitation. We designed and implemented a strategy to build a culture of interdisciplinary communication and collaboration that facilitates translational research across several disciplines in our inpatient rehabilitation hospital. We colocated clinicians and researchers in workspaces within a new hospital and created the Research Accelerator Program-a collection of team-focused initiatives that promote communication and collaboration among researchers, clinicians, and other staff. The purpose of this article is to disseminate this strategy, which has increased staff participation in research activities and increased scientific productivity of interdisciplinary research teams over the past 8 yrs.

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Background: Progressive functional decline is a key element of cancer-associated cachexia. No therapies have successfully translated to the clinic due to an inability to measure and improve physical function in cachectic patients. Major barriers to translating pre-clinical therapies to the clinic include lack of cancer models that accurately mimic functional decline and use of non-specific outcome measures of function, like grip strength. New approaches are needed to investigate cachexia-related function at both the basic and clinical science levels. Methods: Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-ras LSL.G12D/+ ; Trp53 R172H/+ ; Pdx-1-Cre (KPC) derived cells. 128 animals in this new model were then assessed for muscle wasting, inflammation, and functional decline using a battery of biochemical, physiologic, and behavioral techniques. In parallel, we analyzed a 156-subject cohort of cancer patients with a range of cachexia severity, and who required rehabilitation, to determine the relationship between gait speed via six-minute walk test (6MWT), grip strength (hGS), and functional independence measures (FIM). Cachectic patients were identified using the Weight Loss Grading Scale (WLGS), Fearon consensus criteria, and the Prognostic Nutritional Index (PNI). Results: Using a 100-cell dose of DT10022 KPC cells, we extended the survival of the KPC orthotopic model to 8-9 weeks post-implantation compared to higher doses used (p<0.001). In this Low-dose Orthotopic (LO) model, both progressive skeletal and cardiac muscle wasting were detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 weeks post-implantation compared to controls (p<0.001). Gait speed in LO animals declined as early 2 week post-implantation whereas grip strength change was a late event and related to end of life. Principle component analysis (PCA) revealed distinct cachectic and non-cachectic animal populations, which we leveraged to show that gait speed decline was specific to cachexia (p<0.01) while grip strength decline was not (p=0.19). These data paralleled our observations in cancer patients with cachexia who required rehabilitation. In cachectic patients (identified by WLGS, Fearon criteria, or PNI, change in 6MWT correlated with motor FIM score changes while hGS did not (r 2 =0.18, p<0.001). This relationship between 6MWT and FIM in cachectic patients was further confirmed through multivariate regression (r 2 =0.30, p<0.001) controlling for age and cancer burden. Conclusion: Outcome measures linked to gait are better associated with cachexia related function and preferred for future pre-clinical and clinical cachexia studies.

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Purpose: Previous research has demonstrated increased stiffness in the multifidus muscle compared to other paraspinal muscles at the fiber bundle level. We aimed to compare single fiber and fiber bundle passive mechanical properties of multifidus muscle: (1) in 40 patients undergoing primary versus revision surgery and (2) in muscle with mild versus severe fatty infiltration. Methods: The degree of muscle fatty infiltration was graded using the patients' spine magnetic resonance images. Average single fiber and fiber bundle passive mechanical properties across three tests were compared between primary (N = 30) and revision (N = 10) surgery status, between mild and severe fatty infiltration levels, between sexes, and with age from passive stress-strain tests of excised multifidus muscle intraoperative biopsies. Results: At the single fiber level, elastic modulus was unaffected by degree of fatty infiltration or surgery status. Female sex (p = 0.001) and younger age (p = 0.04) were associated with lower multifidus fiber elastic modulus. At the fiber bundle level, which includes connective tissue around fibers, severe fatty infiltration (p = 0.01) and younger age (p = 0.06) were associated with lower elastic modulus. Primary surgery also demonstrated a moderate, but non-significant effect for lower elastic modulus (p = 0.10). Conclusions: Our results demonstrate that female sex is the primary driver for reduced single fiber elastic modulus of the multifidus, while severity of fatty infiltration is the primary driver for reduced elastic modulus at the level of the fiber bundle in individuals with lumbar spine pathology.

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Traumatic muscle injury represents a collection of skeletal muscle pathologies caused by trauma to the muscle tissue and is defined as damage to the muscle tissue that can result in a functional deficit. Traumatic muscle injury can affect people across the lifespan and can result from high stresses and strains to skeletal muscle tissue, often due to muscle activation while the muscle is lengthening, resulting in indirect and non-contact muscle injuries (strains or ruptures), or from external impact, resulting in direct muscle injuries (contusion or laceration). At a microscopic level, muscle fibres can repair focal damage but must be completely regenerated after full myofibre necrosis. The diagnosis of muscle injury is based on patient history and physical examination. Imaging may be indicated to eliminate differential diagnoses. The management of muscle injury has changed within the past 5 years from initial rest, immobilization and (over)protection to early activation and progressive loading using an active approach. One challenge of muscle injury management is that numerous medical treatment options, such as medications and injections, are often used or proposed to try to accelerate muscle recovery despite very limited efficacy evidence. Another challenge is the prevention of muscle injury owing to the multifactorial and complex nature of this injury.

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INTRODUCTION: Developmental disabilities and neuromotor delay adversely affect long-term neuromuscular function and quality of life. Current evidence suggests that early therapeutic intervention reduces the severity of motor delay by harnessing neuroplastic potential during infancy. To date, most early therapeutic intervention trials are of limited duration and do not begin soon after birth and thus do not take full advantage of early neuroplasticity. The Corbett Ryan-Northwestern-Shirley Ryan AbilityLab-Lurie Children's Infant Early Detection, Intervention and Prevention Project (Project Corbett Ryan) is a multi-site longitudinal randomized controlled trial to evaluate the efficacy of an evidence-based physical therapy intervention initiated in the neonatal intensive care unit (NICU) and continuing to 12 months of age (corrected when applicable). The study integrates five key principles: active learning, environmental enrichment, caregiver engagement, a strengths-based approach, and high dosage (ClinicalTrials.gov identifier NCT05568264). METHODS: We will recruit 192 infants at risk for neuromotor delay who were admitted to the NICU. Infants will be randomized to either a standard-of-care group or an intervention group; infants in both groups will have access to standard-of-care services. The intervention is initiated in the NICU and continues in the infant's home until 12 months of age. Participants will receive twice-weekly physical therapy sessions and caregiver-guided daily activities, assigned by the therapist, targeting collaboratively identified goals. We will use various standardized clinical assessments (General Movement Assessment; Bayley Scales of Infant and Toddler Development, 4th Edition (Bayley-4); Test of Infant Motor Performance; Pediatric Quality of Life Inventory Family Impact Module; Alberta Infant Motor Scale; Neurological, Sensory, Motor, Developmental Assessment; Hammersmith Infant Neurological Examination) as well as novel technology-based tools (wearable sensors, video-based pose estimation) to evaluate neuromotor status and development throughout the course of the study. The primary outcome is the Bayley-4 motor score at 12 months; we will compare scores in infants receiving the intervention vs. standard-of-care therapy.

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Musculoskeletal models are valuable for studying and understanding the human body in a variety of clinical applications that include surgical planning, injury prevention, and prosthetic design. Subject-specific models have proven to be more accurate and useful compared to generic models. Nevertheless, it is important to validate all models when possible. To this end, gracilis muscle-tendon parameters were directly measured intraoperatively and used to test model predictions. The aim of this study was to evaluate the benefits and limitations of systematically incorporating subject-specific variables into muscle models used to predict passive force and fiber length. The results showed that incorporating subject-specific values generally reduced errors, although significant errors still existed. Optimization of the modeling parameter "tendon slack length" was explored in two cases: minimizing fiber length error and minimizing passive force error. The results showed that using all subject-specific values yielded the most favorable outcome in both models and optimization cases. However, the trade-off between fiber length error and passive force error will depend on the specific circumstances and research objectives due to significant individual errors. Notably, individual fiber length and passive force errors were as high as 20% and 37% respectively. Finally, the modeling parameter "tendon slack length" did not correlate with any real-world anatomical length.

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PURPOSE: Following pan-brachial plexus injuries, restoration of elbow flexion is widely accepted as the reconstructive priority. A gracilis free functioning muscle transfer (FFMT) can be used to restore elbow flexion alone with insertion into the biceps brachii (BIC) or brachioradialis (BRD) tendons or restore combined elbow and finger flexion with a more distal insertion into the flexor digitorum profundus (FDP) tendons. Using cadaveric experiments, we determined the peak instantaneous moment arm for each insertion option. METHODS: Six simulated gracilis transfer surgeries were performed using both arms of three fresh-frozen full body cadaveric specimens (age: 79 + 10 years. 2 female). The gracilis muscles from both legs were harvested and transferred to the contralateral upper extremity. The elbow was manually moved through three flexion-extension cycles while the instantaneous moment arm was calculated from measurements of gracilis excursion and elbow joint angle for the three distal insertion sites. RESULTS: Peak instantaneous moment arm for all three insertions occurred at an elbow angle between 83° to 92° with a magnitude ranging from 33 mm to 54 mm. The more distal (FDP/BRD) insertions produced a significantly greater (∼1.5 times) peak elbow flexion instantaneous moment arm compared to the BIC insertion. CONCLUSIONS: Based on the instantaneous moment arm, the gracilis FFMT distal insertion locations could result in greater reconstructed elbow flexion strength. In addition, direct measurement of the shape and magnitude of the moment arm curve for differing insertion sites allows high resolution surgical planning and model testing. CLINICAL RELEVANCE: This study presents the first direct experimental quantification of the gracilis FFMT instantaneous moment arm. The experimental evidence supports the use of FDP/BRD insertion locations by providing a quantitative explanation for the increased elbow flexion torque observed clinically in patients with a gracilis FFMT and distal FDP insertion.

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The vast majority of skeletal muscle biomechanical studies have rightly focused on its active contractile properties. However, skeletal muscle passive biomechanical properties have significant clinical impact in aging and disease and are yet incompletely understood. This review focuses on the passive biomechanical properties of the skeletal muscle extracellular matrix (ECM) and suggests aspects of its structural basis. Structural features of the muscle ECM such as perimysial cables, collagen cross-links and endomysial structures have been described, but the way in which these structures combine to create passive biomechanical properties is not completely known. We highlight the presence and organization of perimysial cables. We also demonstrate that the analytical approaches that define passive biomechanical properties are not necessarily straight forward. For example, multiple equations, such as linear, exponential, and polynomial are commonly used to fit raw stress-strain data. Similarly, multiple definitions of zero strain exist that affect muscle biomechanical property calculations. Finally, the appropriate length range over which to measure the mechanical properties is not clear. Overall, this review summarizes our current state of knowledge in these areas and suggests experimental approaches to measuring the structural and functional properties of skeletal muscle.

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Skeletal muscle's isometric contractile properties are one of the classic structure-function relationships in all of biology allowing for extrapolation of single fibre mechanical properties to whole muscle properties based on the muscle's optimal fibre length and physiological cross-sectional area (PCSA). However, this relationship has only been validated in small animals and then extrapolated to human muscles, which are much larger in terms of length and PCSA. The present study aimed to measure directly the in situ properties and function of the human gracilis muscle to validate this relationship. We leveraged a unique surgical technique in which a human gracilis muscle is transferred from the thigh to the arm, restoring elbow flexion after brachial plexus injury. During this surgery, we directly measured subject specific gracilis muscle force-length relationship in situ and properties ex vivo. Each subject's optimal fibre length was calculated from their muscle's length-tension properties. Each subject's PCSA was calculated from their muscle volume and optimal fibre length. From these experimental data, we established a human muscle fibre-specific tension of 171 kPa. We also determined that average gracilis optimal fibre length is 12.9 cm. Using this subject-specific fibre length, we observed an excellent fit between experimental and theorical active length-tension curves. However, these fibre lengths were about half of the previously reported optimal fascicle lengths of 23 cm. Thus, the long gracilis muscle appears to be composed of relatively short fibres acting in parallel that may not have been appreciated based on traditional anatomical methods. KEY POINTS: Skeletal muscle's isometric contractile properties represent one of the classic structure-function relationships in all of biology and allow scaling single fibre mechanical properties to whole muscle properties based on the muscle's architecture. This physiological relationship has only been validated in small animals but is often extrapolated to human muscles, which are orders of magnitude larger. We leverage a unique surgical technique in which a human gracilis muscle is transplanted from the thigh to the arm to restore elbow flexion after brachial plexus injury, aiming to directly measure muscles properties in situ and test directly the architectural scaling predictions. Using these direct measurements, we establish human muscle fibre-specific tension of ∼170 kPa. Furthermore, we show that the gracilis muscle actually functions as a muscle with relatively short fibres acting in parallel vs. long fibres as previously assumed based on traditional anatomical models.

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OBJECTIVE: To evaluate changes in clinicians' use of evidence-based practice (EBP), openness toward EBP, and their acceptance of organizational changes after a rehabilitation hospital transitioned to a new facility designed to accelerate clinician-researcher collaborations. DESIGN: Three repeated surveys of clinicians before, 7-9 months, and 2.5 years after transition to the new facility. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: Physicians, nurses, therapists, and other health care professionals (n=410, 442, and 448 respondents at Times 1, 2, and 3, respectively). INTERVENTIONS: Implementation of physical (architecture, design) and team-focused (champions, leaders, incentives) changes in a new model of care to promote clinician-researcher collaborations. MAIN OUTCOME MEASURES: Adapted versions of the Evidence-Based Practice Questionnaire (EBPQ), the Evidence-Based Practice Attitudes Scale (EBPAS), and the Organizational Change Recipients' Beliefs Scale (OCRBS) were used. Open-ended survey questions were analyzed through exploratory content analysis. RESULTS: Response rates at Times 1, 2, and 3 were 67% (n=410), 69% (n=422), and 71% (n=448), respectively. After accounting for familiarity with the model of care, there was greater reported use of EBP at Time 3 compared with Time 2 (adjusted meant2=3.51, standard error (SE)=0.05; adj. meant3=3.64, SE=0.05; P=.043). Attitudes toward EBPs were similar over time. Acceptance of the new model of care was lower at Time 2 compared with Time 1, but rebounded at Time 3 (adjusted meant1=3.44, SE=0.04; adj. meant2=3.19, SE=0.04; P<.0001; adj. meant3=3.51, SE=0.04; P<.0001). Analysis of open-ended responses suggested that clinicians' optimism for the model of care was greater over time, but continued quality improvement should focus on cultivating communication between clinicians and researchers. CONCLUSIONS: Accelerating clinician-researcher collaborations in a rehabilitation setting requires sustained effort for successful implementation beyond novel physical changes. Organizations must be responsive to clinicians' changing concerns to adapt and sustain a collaborative translational medicine model and allow sufficient time, probably years, for such transitions to occur.

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