Investigating the association between knee osteoarthritis symptoms with pain catastrophizing domains between Hispanics and non-Hispanic Whites.

Knee osteoarthritis (KOA) is a chronic disease accompanied by debilitating symptoms including pain, stiffness, and limited physical functionality, which have been shown to be associated with pain catastrophizing. Previous studies have revealed racial discrepancies in pain catastrophizing, notably between Hispanics and non-Hispanics while pointing to potential health disparities. Using a conceptual model, this study aimed to investigate racial differences in associations between KOA symptoms with specific pain catastrophizing domains (rumination, magnification, and helplessness). Patients with KOA (n = 253; 147 Hispanics, 106 non-Hispanic Whites) completed a survey that included measures of knee symptoms, pain catastrophizing, and demographic variables. Structural equation modeling revealed that among Hispanics, each pain catastrophizing domain (rumination, magnification, and helplessness) was associated with at least two symptomatic experiences, including pain severity and difficulty in physical function. Specifically, pain severity was associated with (a) rumination: ß = 0.48, p < 0.001, (b) magnification: ß = 0.31, p = 0.003; and (c) helplessness: ß = 0.39, p < 0.001). Additionally, a lower score in physical function was associated with higher magnification (ß = 0.26, p = 0.01), and helplessness (ß = 0.25, p = 0.01). Among non-Hispanic White patients, pain severity was further associated with two domains of pain catastrophizing, including rumination (ß = 0.39, p < 0.001) and helplessness (ß = 0.35, p = 0.01). In addition, association pathways for demographic variables revealed that older Hispanics experienced greater challenges with higher pain severity (ß = 0.26, p = 0.01) and greater difficulty with physical function (ß = 0.31, p < 0.001) while Hispanics females experienced higher pain (ß = 0.19, p = 0.03). These findings highlight the importance of designing tailored interventions that consider key demographic factors such as age, and gender, to improve physical function that might alleviate pain catastrophizing among Hispanics with KOA.

Strain-Dependent Diffusivity of Small and Large Molecules in Meniscus.

Due to lack of full vascularization, the meniscus relies on diffusion through the extracellular matrix to deliver small (e.g., nutrients) and large (e.g., proteins) to resident cells. Under normal physiological conditions, the meniscus undergoes up to 20% compressive strains. While previous studies characterized solute diffusivity in the uncompressed meniscus, to date, little is known about the diffusive transport under physiological strain levels. This information is crucial to fully understand the pathophysiology of the meniscus. The objective of this study was to investigate strain-dependent diffusive properties of the meniscus fibrocartilage. Tissue samples were harvested from the central portion of porcine medial menisci and tested via fluorescence recovery after photobleaching to measure diffusivity of fluorescein (332 Da) and 40 K Da dextran (D40K) under 0%, 10%, and 20% compressive strain. Specifically, average diffusion coefficient and anisotropic ratio, defined as the ratio of the diffusion coefficient in the direction of the tissue collagen fibers to that orthogonal, were determined. For all the experimental conditions investigated, fluorescein diffusivity was statistically faster than that of D40K. Also, for both molecules, diffusion coefficients significantly decreased, up to ∼45%, as the strain increased. In contrast, the anisotropic ratios of both molecules were similar and not affected by the strain applied to the tissue. This suggests that compressive strains used in this study did not alter the diffusive pathways in the meniscus. Our findings provide new knowledge on the transport properties of the meniscus fibrocartilage that can be leveraged to further understand tissue pathophysiology and approaches to tissue restoration.

Gene Expression and Chondrogenic Potential of Cartilage Cells: Osteoarthritis Grade Differences.

Recent data suggest that cells isolated from osteoarthritic (OA) cartilage express mesenchymal progenitor cell (MPC) markers that have the capacity to form hyaline-like cartilage tissue. Whether or not these cells are influenced by the severity of OA remains unexplored. Therefore, we analyzed MPC marker expression and chondrogenetic potential of cells from mild, moderate and severe OA tissue. Human osteoarthritic tibial plateaus were obtained from 25 patients undergoing total knee replacement. Each sample was classified as mild, moderate or severe OA according to OARSI scoring. mRNA expression levels of MPC markers-CD105, CD166, Notch 1, Sox9; mature chondrocyte markers-Aggrecan (Acan), Col II A1, hypertrophic chondrocyte and osteoarthritis-related markers-Col I A1, MMP-13 and ALPL were measured at the tissue level (day 0), after 2 weeks of in vitro expansion (day 14) and following chondrogenic in vitro re-differentiation (day 35). Pellet matrix composition after in vitro chondrogenesis of different OA-derived cells was tested for proteoglycans, collagen II and I by safranin O and immunofluorescence staining. Multiple MPC markers were found in OA cartilage resident tissue within a single OA joint with no significant difference between grades except for Notch1, which was higher in severe OA tissues. Expression levels of CD105 and Notch 1 were comparable between OA cartilage-derived cells of different disease grades and bone marrow mesenchymal stem cell (BM-MSC) line (healthy control). However, the MPC marker Sox 9 was conserved after in vitro expansion and significantly higher in OA cartilage-derived cells compared to its levels in the BM-MSC. The in vitro expansion of cartilage-derived cells resulted in enrichment while re-differentiation in reduction of MPC markers for all three analyzed grades. However, only moderate OA-derived cells after the in vitro chondrogenesis resulted in the formation of hyaline cartilage-like tissue. The latter tissue samples were also highly positive for collagen II and proteoglycans with no expression of osteoarthritis-related markers (collagen I, ALPL and MMP13). MPC marker expression did not differ between OA grades at the tissue level. Interestingly after in vitro re-differentiation, only moderate OA-derived cells showed the capacity to form hyaline cartilage-like tissue. These findings may have implications for clinical practice to understand the intrinsic repair capacity of articular cartilage in OA tissues and raises the possibility of these progenitor cells as a candidate for articular cartilage repair.

Procedural Approach to Ultrasound-Guided Geniculate Nerve Blockade for Knee Pain in Patients with OA.

ABSTRACT: Ultrasound-guided genicular nerve block can provide excellent pain control for patients with knee OA. This procedure has the advantage of providing sensory blockade with concomitant sparing of motor compromise, which is observed when the femoral and its lateral femoral cutaneous branches are blocked. Once the geniculate nerve of interest is identified, the operator can use ultrasound guidance to surround nerve fascicles with an injectate mixture of anesthetic and corticosteroid, yielding decreased pain sensation at the joint capsule. Given the role of the geniculate nerve in providing sensory innervation to the joint capsule and knee ligaments, blockade of this nerve can serve as a useful tool for managing patients with acute knee pain secondary to OA.

Using Genomic Techniques in Sports and Exercise Science: Current Status and Future Opportunities.

ABSTRACT: The past two decades have built on the successes of the Human Genome Project identifying the impact of genetics and genomics on human traits. Given the importance of exercise in the physical and psychological health of individuals across the lifespan, using genomics to understand the impact of genes in the sports medicine field is an emerging field. Given the complexity of the systems involved, high-throughput genomics is required to understand genetic variants, their functions, and ultimately their effect on the body. Consequently, genomic studies have been performed across several domains of sports medicine with varying degrees of success. While the breadth of these is great, they focus largely on the following three areas: 1) performance; 2) injury susceptibility; and 3) sports associated chronic conditions, such as osteoarthritis. Herein, we review literature on genetics and genomics in sports medicine, offer suggestions to bolster existing studies, and suggest ways to ideally impact clinical care.

Training, Injury, and Lifestyle Characteristics of Recreational Triathletes.

ABSTRACT: Triathlon is a popular sport among recreational and competitive athletes. As triathletes compete in races ranging from 16 to 140.6 miles and train in three disciplines simultaneously, it is difficult to identify injury risk factors. The aim of this study was to evaluate characteristics of a group of recreational triathletes regarding their medical history, training regimen, and injuries. Thirty-four triathletes completed this survey. We found a wide range of body types, training habits, and lifestyle characteristics. As in previous studies, we found a high rate of injuries in our surveyed triathletes. Injury rates were higher in athletes who had completed a longer race and those who reported higher training times per week. Additionally, many individuals have medical problems, use a variety of supplements, and follow specific dietary restrictions, which need to be considered in addition to training when assessing injury risk and recovery from injury.

Regulatory-compliant conditions during cell product manufacturing enhance in vitro immunomodulatory properties of infrapatellar fat pad-derived mesenchymal stem/stromal cells.

BACKGROUND AIMS: Mesenchymal stem/stromal cell (MSC)-based therapies have gained attention as potential alternatives for multiple musculoskeletal indications based on their trophic and immunomodulatory properties. The infrapatellar fat pad (IFP) serves as a reservoir of MSCs, which play crucial roles modulating inflammatory and fibrotic events at the IFP and its neighboring tissue, the synovium. In an effort to comply with the existing regulatory framework regarding cell-based product manufacturing, we interrogated the in vitro immunomodulatory capacity of human-derived IFP-MSCs processed under different conditions, including a regulatory-compliant protocol, in addition to their response to the inflammatory and fibrotic environments often present in joint disease. METHODS: Immunophenotype, telomere length, transcriptional and secretory immunomodulatory profiles and functional immunopotency assay were assessed in IFP-MSCs expanded in regular fetal bovine serum (FBS)-supplemented medium and side-by-side compared with same-donor cells processed with two media alternatives (i.e., regulatory-compliant pooled human platelet lysate [hPL] and a chemically reinforced/serum-reduced [Ch-R] formulation). Finally, to assess the effects of such formulations on the ability of the cells to respond to pro-inflammatory and pro-fibrotic conditions, all three groups were stimulated ex vivo (i.e., cell priming) with a cocktail containing TNFα, IFNγ and connective tissue growth factor (tumor-initiating cells) and compared with non-induced cohorts assessing the same outcomes. RESULTS: Non-induced and primed IFP-MSCs expanded in either hPL or Ch-R showed distinct morphology in vitro, similar telomere dynamics and distinct phenotypical and molecular profiles when compared with cohorts grown in FBS. Gene expression of IL-8, CD10 and granulocyte colony-stimulating factor was highly enriched in similarly processed IFP-MSCs. Cell surface markers related to the immunomodulatory capacity, including CD146 and CD10, were highly expressed, and secretion of immunomodulatory and pro-angiogenic factors was significantly enhanced with both hPL and Ch-R formulations. Upon priming, the immunomodulatory phenotype was enhanced, resulting in further increase in CD146 and CD10, significant CXCR4 presence and reduction in TLR3. Similarly, transcriptional and secretory profiles were enriched and more pronounced in IFP-MSCs expanded in either hPL or Ch-R, suggesting a synergistic effect between these formulations and inflammatory/fibrotic priming conditions. Collectively, increased indoleamine-2,3-dioxygenase activity and prostaglandin E2 secretion for hPL- and Ch-R-expanded IFP-MSCs were functionally reflected by their robust T-cell proliferation suppression capacity in vitro compared with IFP-MSCs expanded in FBS, even after priming. CONCLUSIONS: Compared with processing using an FBS-supplemented medium, processing IFP-MSCs with either hPL or Ch-R similarly enhances their immunomodulatory properties, which are further increased after exposure to an inflammatory/fibrotic priming environment. This evidence supports the adoption of regulatory-compliant practices during the manufacturing of a cell-based product based on IFP-MSCs and anticipates a further enhanced response once the cells face the pathological environment after intra-articular administration. Mechanistically, the resulting functionally enhanced cell-based product has potential utilization as a novel, minimally invasive cell therapy for joint disease through modulation of local immune and inflammatory events.

Body Composition in Elite Strongman Competitors.

Kraemer, WJ, Caldwell, LK, Post, EM, DuPont, WH, Martini, ER, Ratamess, NA, Szivak, TK, Shurley, JP, Beeler, MK, Volek, JS, Maresh, CM, Todd, JS, Walrod, BJ, Hyde, PN, Fairman, C, and Best, TM. Body composition in elite strongman competitors. J Strength Cond Res 34(12): 3326-3330, 2020-The purpose of this descriptive investigation was to characterize a group of elite strongman competitors to document the body composition of this unique population of strength athletes. Data were collected from eligible competitors as part of a health screening program conducted over 5 consecutive years. Imaging was acquired using dual-energy x-ray absorptiometry (DXA), providing total body measures of fat mass, lean mass, and bone mineral content (BMC). Year to year, testing groups showed a homogenous grouping of anthropometric, body composition, and bone density metrics. Composite averages were calculated to provide an anthropometric profile of the elite strongman competitor (N = 18; mean ± SD): age, 33.0 ± 5.2 years; body height, 187.4 ± 7.1 cm; body mass, 152.9 ± 19.3 kg; body mass index, 43.5 ± 4.8 kg·m; fat mass, 30.9 ± 11.1 kg; lean mass, 118.0 ± 11.7 kg, body fat, 18.7 ± 6.2%, total BMC, 5.23 ± 0.41 kg, and bone mineral density, 1.78 ± 0.14 g·cm. These data demonstrate that elite strongman competitors are among the largest human male athletes, and in some cases, they are at the extreme limits reported for body size and structure. Elite strongman competitors undergo a high degree of mechanical stress, providing further insight into the potent role of physical training in mediating structural remodeling even into adulthood. Such data provide a glimpse into a unique group of competitive athletes pushing the limits not only of human performance but also of human physiology.

The Thoracic Spine in the Overhead Athlete.

Overhead athletes are susceptible to many injuries, particularly in the shoulder and lumbar spine. Due to the heterogeneity of these two regional injuries, it is difficult to pinpoint the exact origin. A potential contributing factor that should be thoroughly evaluated is the thoracic spine. It can be challenging to quantify exactly how much thoracic spine mobility or lack thereof plays a role toward injury. Despite this, when examining mechanics of an overhead athlete, if neuromuscular control of the thorax is impaired, adjacent motion segments often take the brunt of the required movements. This article addresses the need to incorporate the thoracic spine when analyzing the entire kinetic chain. Clinical pearls regarding thoracic neuromuscular control and rehabilitation were explored, as well as a review of recent literature. Further investigation of thoracic spine therapeutic interventions should be considered when treating overhead athletes.

Enthesopathy-An Underappreciated Role in Osteoarthritis?

Osteoarthritis (OA) continues to be a debilitating disease worldwide, to date, no therapies have been definitely proven to modify disease progression or moderate symptom relief long term other than joint replacement. A contributing factor may be the lack of attention to the potential role of the periarticular enthesis and development and progression of OA. The enthesis is the site of attachment for a tendon, ligament, or joint capsule to the bony skeleton, thereby allowing centralized transmission and dissipation of mechanical loads. Because of this design, the enthesis is a site of stress concentration subject to inflammation during sports-related activities or spondyloarthropathies, which may lead to long-term degeneration. Our hypothesis is that functional incompetence of the enthesis resulting from either degenerative or inflammatory changes could be an initiating factor for OA and may thus provide a novel basis for the development of future disease management in this phenotype of patients.

Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models.

Regular physical activity has been suggested as having both preventive and therapeutic benefits for individuals with osteoarthritis (OA). However, evidence of whether exercise and which type of exercise constitutes a benefit or a risk in the development and progression of OA remains debatable. This may be due to the evaluation of the effect of physical activity or new disease-modifying OA drugs which is currently based on radiographic criteria (eg, joint space width) and the lack of correlation with clinical signs and symptoms (eg, pain and loss of function). Moreover, OA typically manifests itself as changes within the joint space and subchondral bone as well as the whole joint structure, including progressive degradation of cartilage, menisci, ligaments, and synovial inflammation. Biomarkers are being developed to quantify joint remodeling and disease progression notably involving the articular cartilage and synovial fluid. The primary purpose of this review was to evaluate the current literature and to provide further insight based on OA biomarkers and the role physical activity plays in the management of OA. Osteoarthritis biomarkers together with radiographic imaging evidence will ideally guide healthcare providers to incorporate exercise recommendations into clinical management and offer patients evidence-based and individually tailored exercise prescriptions.

An Exploratory Electromyography-Based Coactivation Index for the Cervical Spine.

Objective Develop a coactivation index for the neck and test its effectiveness with complex dynamic head motions. Background Studies describing coactivation for the cervical spine are sparse in the literature. Of those in existence, they were either limited to a priori definitions of agonist/antagonist activity that limited the testing to sagittal and lateral planes or consisted of isometric exertions. Multiplanar movements would allow for a more realistic understanding of naturalistic movements in the cervical spine and propensity for neck pain. However, a gap in the literature exists in which a method to describe coactivation during complex dynamic motions does not exist for the cervical spine. Methods An electromyography-based coactivation index was developed for the cervical spine based on previously tested methodology used on the lumbar spine without a high-end model and tested using a series of different postures and speeds. Results Complex motions involving twisting (i.e., flexion and twisting) and higher speed had higher magnitudes of coactivation than uniplanar motions in the sagittal or lateral plane, which was expected. The coupled motion of flexion and twisting showed four to five times higher coactivation than uniplanar (sagittal or lateral) movements. Conclusion The coactivation index developed accommodates multiplanar, naturalistic movements. Testing of the index showed that motions requiring higher degrees of head control had higher effort due to coactivation, which was expected. Application Overall, this coactivation index may be utilized to understand the neuromuscular effort of various tasks in the cervical spine.

Development of a lumbar EMG-based coactivation index for the assessment of complex dynamic tasks.

The objective of this study was to develop and test an EMG-based coactivation index and compare it to a coactivation index defined by a biologically assisted lumbar spine model to differentiate between tasks. The purpose was to provide a universal approach to assess coactivation of a multi-muscle system when a computational model is not accessible. The EMG-based index developed utilised anthropometric-defined muscle characteristics driven by torso kinematics and EMG. Muscles were classified as agonists/antagonists based upon 'simulated' moments of the muscles relative to the total 'simulated' moment. Different tasks were used to test the range of the index including lifting, pushing and Valsalva. Results showed that the EMG-based index was comparable to the index defined by a biologically assisted model (r2 = 0.78). Overall, the EMG-based index provides a universal, usable method to assess the neuromuscular effort associated with coactivation for complex dynamic tasks when the benefit of a biomechanical model is not available. Practitioner Summary: A universal coactivation index for the lumbar spine was developed to assess complex dynamic tasks. This method was validated relative to a model-based index for use when a high-end computational model is not available. Its simplicity allows for fewer inputs and usability for assessment of task ergonomics and rehabilitation.

Progenitor Cells from Cartilage: Grade Specific Differences in Stem Cell Marker Expression.

Recent research has confirmed the presence of Mesenchymal stem cell (MSC)-like progenitors (MPC) in both normal and osteoarthritic cartilage. However, there is only limited information concerning how MPC markers are expressed with osteoarthritis (OA) progression. The purpose of this study was to compare the prevalence of various MPC markers in different OA grades. Human osteoarthritic tibial plateaus were obtained from ten patients undergoing total knee replacement. Each sample had been classified into a mild or severe group according to OARSI scoring. Tissue was taken from each specimen and mRNA expression levels of CD105, CD166, Notch 1, Sox9, Acan and Col II A1 were measured at day 0 and day 14 (2 weeks in vitro). Furthermore, MSC markers: Nucleostemin, CD90, CD73, CD166, CD105 and Notch 1 were studied by immunofluorescence. mRNA levels of MSC markers did not differ between mild and severe OA at day 0. At day 14, protein analysis showed that proliferated cells from both sources expressed all 6 MSC markers. Only cells from the mild OA subjects resulted in a significant increase of mRNA CD105 and CD166 after in vitro expansion. Moreover, cells from the mild OA subjects showed significantly higher levels of CD105, Sox9 and Acan compared with those from severe OA specimens. Results confirmed the presence of MSC markers in mild and severe OA tissue at both mRNA and protein levels. We found significant differences between cells obtained from mild compared to severe OA specimens suggests that mild OA derived cells may have a greater MSC potential.

Triathlon Injuries: Transitioning from Prevalence to Prediction and Prevention.

The Ironman triathlon began in Hawaii in 1978 with 50 participants. Since then, the race has continued to grow in popularity. Injuries are very common among triathletes. Studies have looked at the relationship between injuries and many different factors. Sex, age, and morphological characteristics, such as height, weight, and body mass index, have not been shown to correlate with injury. The association between training volume and injury has shown inconsistent results. This could be due to multiple factors in study design including definitions and evaluation of training volume. Recent literature highlights the complex relationship between risk factors and injury occurrence. This article reviews the epidemiology and risk factors for musculoskeletal injuries in Ironman distance triathletes as well as general research and theories on training volume assessment and injury risk to provide recommendations for future studies and strategies for injury prevention.

Not Missing the Future: A Call to Action for Investigating the Role of Regenerative Medicine Therapies in Pediatric/Adolescent Sports Injuries.

In August 2016, a group including sport medicine clinicians, researchers, and a bioethicist met in Vail, Colorado to discuss regenerative medicine and its potential role in youth sports injuries. There was consensus that a call to action is urgently needed to understand the current evidence base, the risks and rewards, and future directions of research and clinical practice for regenerative medicine therapies in youth sports. We present here a summary of our meeting, which was supported by the National Youth Sports Health and Safety Institute (NYSHSI), a partnership between the American College of Sports Medicine (ACSM) and Sanford Health. The group's goal is to educate practitioners and the public, and to pioneer a means of accumulating meaningful clinical data on regenerative medicine therapies in pediatric and adolescent athletes.

Physical Exam Risk Factors for Lower Extremity Injury in High School Athletes: A Systematic Review.

OBJECTIVE: A stated goal of the preparticipation physical evaluation (PPE) is to reduce musculoskeletal injury, yet the musculoskeletal portion of the PPE is reportedly of questionable use in assessing lower extremity injury risk in high school-aged athletes. The objectives of this study are: (1) identify clinical assessment tools demonstrated to effectively determine lower extremity injury risk in a prospective setting, and (2) critically assess the methodological quality of prospective lower extremity risk assessment studies that use these tools. DATA SOURCES: A systematic search was performed in PubMed, CINAHL, UptoDate, Google Scholar, Cochrane Reviews, and SportDiscus. Inclusion criteria were prospective injury risk assessment studies involving athletes primarily ages 13 to 19 that used screening methods that did not require highly specialized equipment. Methodological quality was evaluated with a modified physiotherapy evidence database (PEDro) scale. MAIN RESULTS: Nine studies were included. The mean modified PEDro score was 6.0/10 (SD, 1.5). Multidirectional balance (odds ratio [OR], 3.0; CI, 1.5-6.1; P < 0.05) and physical maturation status (P < 0.05) were predictive of overall injury risk, knee hyperextension was predictive of anterior cruciate ligament injury (OR, 5.0; CI, 1.2-18.4; P < 0.05), hip external:internal rotator strength ratio of patellofemoral pain syndrome (P = 0.02), and foot posture index of ankle sprain (r = -0.339, P = 0.008). CONCLUSIONS: Minimal prospective evidence supports or refutes the use of the functional musculoskeletal exam portion of the current PPE to assess lower extremity injury risk in high school athletes. Limited evidence does support inclusion of multidirectional balance assessment and physical maturation status in a musculoskeletal exam as both are generalizable risk factors for lower extremity injury.

Epidemiology of meniscal injuries in US high school athletes between 2007 and 2013.

PURPOSE: Knowledge of epidemiologic trends of meniscal injuries in young active populations is limited. Better awareness of injury patterns is a first step to lowering injury rates. Our hypothesis was that meniscal injuries in high school athletes would vary by gender, sport, and type of exposure. METHODS: During the 2007/2008 and 2012/2013 academic years, a large nationally disperse sample of US high schools reported athlete exposure and injury data for 22 sports by having certified athletic trainers complete an internet-based data collection tool. RESULTS: One thousand and eighty-two meniscal injuries were reported during 21,088,365 athlete exposures for an overall injury rate of 5.1 per 100,000 athlete exposures. The overall rate of injury was higher in competition (11.9) than practice (2.7) (RR = 4.4; 95% CI 3.9-5.0), and 12/19 sports showed significantly higher injury rates in competition compared to practice. Of all injuries, 68.0% occurred in boys, yet among the gender-comparable sports of soccer, basketball, track and field, lacrosse, and baseball/softball injury rates were higher for girls than boys (5.5 and 2.5, respectively, RR = 2.2; 95% CI 1.8-2.7). Contact injury represented the most common mechanism (55.9%). Surgery was performed for the majority of injuries (63.8%), and 54.0% of athletes had associated intra-articular knee pathology. CONCLUSIONS: Meniscal injury patterns among high school athletes vary by gender, sport, and type of exposure. Our study is clinically relevant because recognition of distinct differences in these injury patterns will help drive evidence-based, targeted injury prevention strategies and efforts. LEVEL OF EVIDENCE: III.

Muscle Forces and Their Contributions to Vertical and Horizontal Acceleration of the Center of Mass During Sit-to-Stand Transfer in Young, Healthy Adults.

Sit-to-stand transfer is a common task that is challenging for older adults and others with musculoskeletal impairments. Associated joint torques and muscle activations have been analyzed two-dimensionally, neglecting possible three-dimensional (3D) compensatory movements in those who struggle with sit-to-stand transfer. Furthermore, how muscles accelerate an individual up and off the chair remains unclear; such knowledge could inform rehabilitation strategies. We examined muscle forces, muscleinduced accelerations, and interlimb muscle force differences during sit-to-stand transfer in young, healthy adults. Dynamic simulations were created using a custom 3D musculoskeletal model; static optimization and induced acceleration analysis were used to determine muscle forces and their induced accelerations, respectively. The gluteus maximus generated the largest force (2009.07 ± 277.31 N) and was a main contributor to forward acceleration of the center of mass (COM) (0.62 ± 0.18 m/s(2)), while the quadriceps opposed it. The soleus was a main contributor to upward (2.56 ± 0.74 m/s(2)) and forward acceleration of the COM (0.62 ± 0.33 m/s(2)). Interlimb muscle force differences were observed, demonstrating lower limb symmetry cannot be assumed during this task, even in healthy adults. These findings establish a baseline from which deficits and compensatory strategies in relevant populations (eg, elderly, osteoarthritis) can be identified.

Po2 cycling protects diaphragm function during reoxygenation via ROS, Akt, ERK, and mitochondrial channels.

Po2 cycling, often referred to as intermittent hypoxia, involves exposing tissues to brief cycles of low oxygen environments immediately followed by hyperoxic conditions. After experiencing long-term hypoxia, muscle can be damaged during the subsequent reintroduction of oxygen, which leads to muscle dysfunction via reperfusion injury. The protective effect and mechanism behind Po2 cycling in skeletal muscle during reoxygenation have yet to be fully elucidated. We hypothesize that Po2 cycling effectively increases muscle fatigue resistance through reactive oxygen species (ROS), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and certain mitochondrial channels during reoxygenation. Using a dihydrofluorescein fluorescent probe, we detected the production of ROS in mouse diaphragmatic skeletal muscle in real time under confocal microscopy. Muscles treated with Po2 cycling displayed significantly attenuated ROS levels (n = 5; P < 0.001) as well as enhanced force generation compared with controls during reperfusion (n = 7; P < 0.05). We also used inhibitors for signaling molecules or membrane channels such as ROS, Akt, ERK, as well as chemical stimulators to close mitochondrial ATP-sensitive potassium channel (KATP) or open mitochondrial permeability transition pore (mPTP). All these blockers or stimulators abolished improved muscle function with Po2 cycling treatment. This current investigation has discovered a correlation between KATP and mPTP and the Po2 cycling pathway in diaphragmatic skeletal muscle. Thus we have identified a unique signaling pathway that may involve ROS, Akt, ERK, and mitochondrial channels responsible for Po2 cycling protection during reoxygenation conditions in the diaphragm.