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ObjectiveFear of falling is an important problem among older adults, even those with relatively low rates of objective fall risk, who are often overlooked as targets for intervention.MethodWe developed and pilot tested a new intervention, Activity, Balance, Learning, and Exposure (ABLE), in a sample of 10 older adults with excessive fear of falling. The ABLE intervention integrates exposure therapy and cognitive restructuring with a home safety evaluation and an exercise program and is conducted in the home. In this pilot project, ABLE was jointly conducted by a physical therapist and a psychologist with expertise in geriatric anxiety disorders.ResultsThe intervention was feasible and acceptable and resulted in decreases in fear and activity avoidance for most participants. One participant experienced an injurious fall.DiscussionWe learned a number of important lessons resulting in modifications to the inclusion criteria, assessments, and intervention over the course of this pilot study. Results suggest that ABLE has promise for treating excessive fear of falling in the elderly and support testing the intervention in a larger randomized trial. Copyright © 2016 John Wiley & Sons, Ltd.

Achieving functional restoration of diseased or injured tissues is the ultimate goal of both regenerative medicine approaches and physical therapy interventions. Proper integration and healing of the surrogate cells, tissues, or organs introduced using regenerative medicine techniques are often dependent on the co-introduction of therapeutic physical stimuli. Thus, regenerative rehabilitation represents a collaborative approach whereby rehabilitation specialists, basic scientists, physicians, and surgeons work closely to enhance tissue restoration by creating tailored rehabilitation treatments. One of the primary treatment regimens that physical therapists use to promote tissue healing is the introduction of mechanical forces, or mechanotherapies. These mechanotherapies in regenerative rehabilitation activate specific biological responses in musculoskeletal tissues to enhance the integration, healing, and restorative capacity of implanted cells, tissues, or synthetic scaffolds. To become future leaders in the field of regenerative rehabilitation, physical therapists must understand the principles of mechanobiology and how mechanotherapies augment tissue responses. This perspective article provides an overview of mechanotherapy and discusses how mechanical signals are transmitted at the tissue, cellular, and molecular levels. The synergistic effects of physical interventions and pharmacological agents also are discussed. The goals are to highlight the critical importance of mechanical signals on biological tissue healing and to emphasize the need for collaboration within the field of regenerative rehabilitation. As this field continues to emerge, physical therapists are poised to provide a critical contribution by integrating mechanotherapies with regenerative medicine to restore musculoskeletal function.

Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1- and ESRR-induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno-associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4-wk-old mice. Compared to control vector, AAV1-Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40-80%). Moreover, AAV1-Perm1-transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31%, respectively), without prominent changes in fiber-type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.

Vertebral level-dependent, angular, and linear translations of the spine have been measured in 2D and 3D using several imaging methods to quantify postural changes due to loading conditions and tasks. Here, we propose and validate a semiautomated method for measuring lumbar intervertebral angles and translations from upright MRI images using an endplate-based, joint coordinate system (JCS). This method was validated using 3D printed structures, representing intervertebral discs (IVD) at predetermined angles and heights, which were positioned between adjacent cadaveric vertebrae as a gold standard. Excellent agreement between our measurements and the gold standard was found for intervertebral angles in all anatomical planes (ICC > .997) and intervertebral distance measurements (ICC > .949). The proposed endplate-based JCS was compared with the vertebral body-based JCS proposed by the International Society of Biomechanics (ISB) using the 3D printed structures placed between 3 adjacent vertebrae from a cadaver with scoliosis. The endplate-based method was found to have better agreement with angles in the sagittal plane (ICC = 0.985) compared with the vertebral body-based method (ICC = .280). Thus, this method is accurate for measuring 3D intervertebral angles in the healthy and diseased lumbar spine.

BackgroundSacroiliac joint (SI) pain is increasingly being recognized as a source of low back pain. Injections and percutaneous type procedures are performed to treat symptomatic joints. However, there are limited studies available assessing the anatomy of the SI joint in vivo among patients with pain.ObjectivesThe purpose of this study was to provide more precise information on the dimensions and orientation of the SI joint using a new technique for the radiographic evaluation of this joint.Study designObservational study.SettingEmergency departmentMethodsThree dimensional computed tomographic (CT) reconstructions of the pelvis were formatted from 100 SI joints in 50 patients who had clinically indicated abdominal/pelvic scans. These images were manipulated to evaluate the SI joint in multiple planes and measure its dimensions, area, and relationship to anatomic landmarks such as the anterior superior iliac spine (ASIS) and posterior superior iliac spine (PSIS).ResultsOf the 50 patients, 23 were men and 27 women. Their mean age was 47.6 years (± 18.1). The SI joint consists of a superior limb which measures 39.7 mm (± 4.8) in length, and an inferior limb which measures 54.3 mm (± 5.1), oriented at an angle of 100.1° (± 8.1) to one another. The mean area of the joint was 1276.8 mm2 (± 189.8). The horizontal distance from the ASIS to the front of the superior SI joint is 75.4 mm (± 8.4). The horizontal distance from the PSIS to the back of the superior SI joint is 43.9 mm (± 5.6). The joint stretches 7.5 mm (± 5.9) cephalad and 38.1 mm (± 6.4) caudal to the PSIS, and 35.4 mm (± 8.8) cephalad and 10.2 mm (± 11.4) caudal to the ASIS.LimitationsCT scans were performed with patients lying supine, while most SI joint procedures are performed with a patient prone. However it is doubtful that the bony anatomic landmarks would change appreciable in this largely immobile joint. These patients were seen in the emergency department for a variety of conditions related to abdominal and pelvic pain, and not exclusively for SI joint pain.ConclusionsTreatment of the SI joint by surgeons and interventionalists is hampered by the limited number of anatomic studies in the literature. Our study presents the SI joint as a 2-limbed structure, sitting from slightly above the level of the PSIS rostrally to slightly below the level of the ASIS caudally. Palpation of these landmarks may assist in directing physicians to the joint. To begin an interventional pain procedure, with a patient lying prone, this data supports tilting the x-ray image intensifier 10 degrees caudal past the vertical anteroposterior (AP) view for optimal approach of the SI joint's inferior limb. The needle entry should be about 44.1 mm (1.75 inches) caudal to the PSIS. The image intensifier should have a 12 degree left lateral oblique view for injection of the right SI joint, and a 12 degree right lateral oblique view for the left SI joint.

BackgroundChronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear.Purpose/hypothesisThe purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair.Study designControlled laboratory study.MethodsChronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro-computed tomography.ResultsAll repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered trabecular structure, and the repair had decreased strength, stiffness, and toughness, compared with the acute injury and repair group.ConclusionChronic degenerative changes in rotator cuff muscles, tendons, and bone led to inferior healing characteristics after repair compared with acute injuries and repair. The changes were not reversible after repair in the time course studied, consistent with clinical impressions.Clinical relevanceHigh retear rates after rotator cuff repair are associated with tear size and chronicity. Understanding the mechanisms behind this association may allow for targeted tissue therapy for tissue degeneration that occurs in the setting of chronic tears.

Rotator cuff (RC) disease is an extremely common condition associated with shoulder pain, reduced functional capacities, and impaired quality of life. It primarily involves alterations in tendon health and mechanical properties that can ultimately lead to tendon failure. RC tendon tears induce progressive muscle changes that have a negative impact on surgical reparability of the RC tendons and clinical outcomes. At the same time, a significant base of clinical data suggests a relatively weak relationship between RC integrity and clinical presentation, emphasizing the multifactorial aspects of RC disease. This review aims to summarize the potential contribution of peripheral, spinal, and supraspinal neural factors that may (1) exacerbate structural and functional muscle changes induced by tendon tear, (2) compromise the reversal of these changes during surgery and rehabilitation, (3) contribute to pain generation and persistence of pain, (4) impair shoulder function through reduced proprioception, kinematics, and muscle recruitment, and (5) help explain interindividual differences and response to treatment. Given the current clinical and scientific interest in peripheral nerve injury in the context of RC disease and surgery, we carefully reviewed this body of literature with a particular emphasis on suprascapular neuropathy that has generated a large number of studies in the past decade. Within this process, we highlight the gaps in current knowledge and suggest research avenues for scientists and clinicians.

Muscle contractures that occur after upper motor neuron lesion are often surgically released or lengthened. However, surgical manipulation of muscle length changes a muscle's sarcomere length (Ls ), which can affect force production. To predict effects of surgery, both macro- (fascicle length (Lf )) and micro- (Ls ) level structural measurements are needed. Therefore, the purpose of this study was to quantify both Ls and Lf in patients with cerebral palsy (CP) as well as typically developing (TD) children. Soleus ultrasound images were obtained from children with CP and TD children. Lf was determined and, with the joint in the same position, CP biopsies were obtained and formalin fixed, and Ls was measured by laser diffraction. Since soleus Ls values were not measurable in TD children, TD Ls values were obtained using three independent methods. While average Lf did not differ between groups (CP=3.6±1.2 cm, TD=3.5±0.9 cm; p>0.6), Ls was dramatically longer in children with CP (4.07±0.45 µm vs. TD=2.17±0.24 µm; p

BackgroundRotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology.MethodsBiopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis.ResultsPatients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear.ConclusionsGene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis.Clinical relevanceThese data highlight the difficulty in treating massive tears and suggest that the timing of treatment may be important for muscle recovery. Specifically, earlier interventions to address tendon injury may allow muscles to respond more appropriately to mechanical stimuli.

Rotator cuff tears can cause irreversible changes (e.g., fibrosis) to the structure and function of the injured muscle(s). Fibrosis leads to increased muscle stiffness resulting in increased tension at the rotator cuff repair site. This tension influences repairability and healing potential in the clinical setting. However, the micro- and meso-scale structural and molecular sources of these whole-muscle mechanical changes are poorly understood. Here, single muscle fiber and fiber bundle passive mechanical testing was performed on rat supraspinatus and infraspinatus muscles with experimentally induced massive rotator cuff tears (Tenotomy) as well as massive tears with chemical denervation (Tenotomy + BTX) at 8 and 16 weeks post-injury. Titin molecular weight, collagen content, and myosin heavy chain profiles were measured and correlated with mechanical variables. Single fiber stiffness was not different between controls and experimental groups. However, fiber bundle stiffness was significantly increased at 8 weeks in the Tenotomy + BTX group compared to Tenotomy or control groups. Many of the changes were resolved by 16 weeks. Only fiber bundle passive mechanics was weakly correlated with collagen content. These data suggest that tendon injury with concomitant neuromuscular compromise results in extra-cellular matrix production and increases in stiffness of the muscle, potentially complicating subsequent attempts for surgical repair.

Exercise‐induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise‐induced phenotypes. Using this network, we formulated a logic‐based ordinary differential equation model predicting time‐dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP‐activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross‐talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes. What is the central question of this study?How do the cell signalling pathways regulating skeletal myocyte responses to resistance and endurance exercise interact?What is the main finding and its importance?A new systems model of skeletal muscle signalling pathways activated by resistance and endurance training was developed with eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise‐induced phenotypes. The model accurately predicted 85% of independent measurements for resistance exercise and 75% for endurance training. Analysis revealed pathways regulating the preferential activation of protein synthesis and cell growth by resistance training and inflammation by endurance exercise. [ABSTRACT FROM AUTHOR]

BackgroundMetatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer.Methods23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age-matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance.FindingsThe diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), P1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers.InterpretationIndividuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown.

Abstract Background Cerebral palsy (CP) is an upper motor neuron disease that results in a progressive movement disorder. Secondary to the neurological insult, muscles from CP patients often become spastic. Spastic muscle is characterized by an increased resistance to stretch, but often develops the further complication of contracture which represents a prominent disability in children with CP. This study's purpose is to characterize alterations of spastic muscle on the transcriptional level. Increased knowledge of spastic muscle may lead to novel therapies to improve the quality of life for children with CP. Method The transcriptional profile of spastic muscles were defined in children with cerebral palsy and compared to control patients using Affymetrix U133A chips. Expression data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for select genes. Significant genes were determined using a 2 × 2 ANOVA and results required congruence between 3 preprocessing algorithms. Results CP patients clustered independently and 205 genes were significantly altered, covering a range of cellular processes. Placing gene expression in the context of physiological pathways, the results demonstrated that spastic muscle in CP adapts transcriptionally by altering extracellular matrix, fiber type, and myogenic potential. Extracellular matrix adaptations occur primarily in the basal lamina although there is increase in fibrillar collagen components. Fiber type is predominately fast compared to normal muscle as evidenced by contractile gene isoforms and decrease in oxidative metabolic gene transcription, despite a paradoxical increased transcription of slow fiber pathway genes. We also found competing pathways of fiber hypertrophy with an increase in the anabolic IGF1 gene in parallel with a paradoxical increase in myostatin, a gene responsible for stopping muscle growth. We found evidence that excitation-contraction coupling genes are altered in muscles from patients with CP and may be a significant component of disease. Conclusion This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise‐based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine‐based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non‐exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub‐cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non‐exercised cohort, with similar patterns in the matched sub‐analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate‐high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair (n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks postrepair. [ABSTRACT FROM AUTHOR]