The Use of Musculoskeletal Ultrasound for the Diagnosis of Groin and Hip Pain in Athletes.

Athletes are particularly predisposed to injuries in the groin and pelvic region. Men in particular are predisposed to injuries like hernias in the inguinal region. The increased demands and training load on today's athletes combined with individual factors may create the environment for these injuries. Five areas categorize the pain present from different pathological entities in this region: adductor-related, iliopsoas-related, inguinal-related, pubic-related, and hip-related groin pain. It has been extremely difficult in the past to accurately diagnose what has been previously labeled sports hernia, sportsman's groin, or inguinal disruption. Therefore, this article describes the methods and procedures used for diagnostic ultrasound (US) and differentiation between these entities from one practice based on the most current research in musculoskeletal US.

Inducible and reversible SOD2 knockdown in mouse skeletal muscle drives impaired pyruvate oxidation and reduced metabolic flexibility.

Highlights: SOD2 knockdown and recovery is achieved in skeletal muscle by using a shRNA targeted to SOD2 mRNA controlled by a tetracycline Response Element and reverse tetracycline transactivator proteinSOD2 KD is induced by administering doxycycline in the drinking waterMitochondrial functional decline and recovery follows the time course of SOD2 protein decline and recoverySustained SOD2 KD precipitates reduced metabolic flexibility in skeletal muscle mitochondria characterized by impaired pyruvate respiration in the presence of other substrates. Introduction: Skeletal muscle mitochondrial dysfunction is a key characteristic of aging muscle and contributes to age related diseases such as sarcopenia, frailty, and type 2 diabetes. Mitochondrial oxidative distress has been implicated as a driving factor in these age-related diseases, however whether it is a cause, or a consequence of mitochondrial dysfunction remains to be determined. The development of more flexible genetic models is an important tool to test the mechanistic role of mitochondrial oxidative stress on skeletal muscle metabolic dysfunction. We characterize a new model of inducible and reversible mitochondrial redox stress using a tetracycline controlled skeletal muscle specific short hairpin RNA targeted to superoxide dismutase 2 (iSOD2). Methods: iSOD2 KD and control (CON) animals were administered doxycycline for 3-or 12-weeks and followed for up to 24 weeks and mitochondrial respiration and muscle contraction were measured to define the time course of SOD2 KD and muscle functional changes and recovery. Results: Maximum knockdown of SOD2 protein occurred by 6 weeks and recovered by 24 weeks after DOX treatment. Mitochondrial aconitase activity and maximum mitochondrial respiration declined in KD muscle by 12 weeks and recovered by 24 weeks. There were minimal changes in gene expression between KD and CON muscle. Twelve-week KD showed a small, but significant decrease in muscle fatigue resistance. The primary phenotype was reduced metabolic flexibility characterized by impaired pyruvate driven respiration when other substrates are present. The pyruvate dehydrogenase kinase inhibitor dichloroacetate partially restored pyruvate driven respiration, while the thiol reductant DTT did not. Conclusion: We use a model of inducible and reversible skeletal muscle SOD2 knockdown to demonstrate that elevated matrix superoxide reversibly impairs mitochondrial substrate flexibility characterized by impaired pyruvate oxidation. Despite the bioenergetic effect, the limited change in gene expression suggests that the elevated redox stress in this model is confined to the mitochondrial matrix.

A novel mitochondrial complex I ROS inhibitor partially improves muscle regeneration in adult but not old mice.

It is unclear whether mitochondrial dysfunction and redox stress contribute to impaired age-related muscle regenerative capacity. Here we characterized a novel compound, BI4500, that inhibits the release of reactive oxygen species (ROS) from the quinone site in mitochondrial complex I (site IQ). We tested the hypothesis that ROS release from site IQ contributes to impaired regenerative capacity in aging muscle. Electron transfer system site-specific ROS production was measured in adult and aged mouse isolated muscle mitochondria and permeabilized gastrocnemius fibers. BI4500 inhibited ROS production from site IQ in a concentration-dependent manner (IC50 = âˆ¼985 nM) by inhibiting ROS release without impairing complex I-linked respiration. In vivo BI4500 treatment decreased ROS production from site IQ. Muscle injury and sham injury were induced using barium chloride or vehicle injection to the tibialis anterior (TA) muscle in adult and aged male mice. On the same day as injury, mice began a daily gavage of 30 mg/kg BI4500 (BI) or placebo (PLA). Muscle regeneration (H&E, Sirius Red, Pax7) was measured at 5 and 35 days after injury. Muscle injury increased centrally nucleated fibers (CNFs) and fibrosis with no treatment or age effect. There was a significant age by treatment interaction for CNFs at 5- and 35-days post injury with significantly more CNFs in BI adults compared to PLA adults. Muscle fiber cross-sectional area (CSA) recovered significantly more in adult BI mice (-89 ± 365 µm2) compared to old PLA (-599 ± 153 µm2) and old BI (-535 ± 222 µm2, mean ± SD). In situ TA force recovery was measured 35 days after injury and was not significantly different by age or treatment. Inhibition of site IQ ROS partially improves muscle regeneration in adult but not old muscle demonstrating a role for CI ROS in the response to muscle injury. Site IQ ROS does not contribute to impaired regenerative capacity in aging.

High intensity muscle stimulation activates a systemic Nrf2-mediated redox stress response.

High intensity exercise is a popular mode of exercise to elicit similar or greater adaptive responses compared to traditional moderate intensity continuous exercise. However, the molecular mechanisms underlying these adaptive responses are still unclear. The purpose of this pilot study was to compare high and low intensity contractile stimulus on the Nrf2-mediated redox stress response in mouse skeletal muscle. An intra-animal design was used to control for variations in individual responses to muscle stimulation by comparing a stimulated limb (STIM) to the contralateral unstimulated control limb (CON). High Intensity (HI - 100Hz), Low Intensity (LI - 50Hz), and Naïve Control (NC - Mock stimulation vs CON) groups were used to compare these effects on Nrf2-ARE binding, Keap1 protein, and downstream gene and protein expression of Nrf2 target genes. Muscle stimulation significantly increased Nrf2-ARE binding in LI-STIM compared to LI-CON (p = 0.0098), while Nrf2-ARE binding was elevated in both HI-CON and HI-STIM compared to NC (p = 0.0007). The Nrf2-ARE results were mirrored in the downregulation of Keap1, where Keap1 expression in HI-CON and HI-STIM were both significantly lower than NC (p = 0.008) and decreased in LI-STIM compared to LI-CON (p = 0.015). In addition, stimulation increased NQO1 protein compared to contralateral control regardless of stimulation intensity (p = 0.019), and HO1 protein was significantly higher in high intensity compared to the Naïve control group (p = 0.002). Taken together, these data suggest a systemic redox signaling exerkine is activating Nrf2-ARE binding and is intensity gated, where Nrf2-ARE activation in contralateral control limbs were only seen in the HI group. Other research in exercise induced Nrf2 signaling support the general finding that Nrf2 is activated in peripheral tissues in response to exercise, however the specific exerkine responsible for the systemic signaling effects is not known. Future work should aim to delineate these redox sensitive systemic signaling mechanisms.

Aerobic exercise training partially reverses the impairment of Nrf2 activation in older humans.

Nuclear factor erythroid-2-related factor 2 (Nrf2), is an inducible transcription factor that improves redox balance through stimulating antioxidant gene expression. In older humans the Nrf2 response to a single bout of acute exercise is blunted compared to young indicating impaired redox signaling. The purpose of this randomized controlled trial was to investigate if the signaling impairment could be reversed with exercise training in older men and women, while also comparing to young. Young (18-28y, n = 21) and older (≥60y, n = 19) men and women were randomized to 8-week aerobic exercise training (ET; 3 d/wk, 45 min/d) or a non-exercise control group (CON). Nrf2 nuclear localization, gene expression for NQO1, HO1, and GCLC, and GCLC protein were measured in PBMCs in response to acute exercise trial (AET; 30-min cycling at 70% VO2 peak pre- and post-intervention at 7 timepoints (Pre, +10 m, +30 m, +1 h, +4 h, +8 h, +24 h). Young had greater Nrf2 signaling response compared to older at pre-intervention (p = 0.05), whereas the older had significantly higher basal Nrf2 levels (p = 0.004). ET decreased basal Nrf2 expression compared to CON (p = 0.032) and improved the Nrf2 signaling response in both young and older (p < 0.05). The degree of restoration in Nrf2 signaling response was related to the degree of change in basal Nrf2 (p = 0.039), which was driven by older adults (p = 0.014). Lower basal nuclear Nrf2 levels were associated with changes seen in AET responses for Nrf2 and GCLC protein, as well as NQO1 and GCLC mRNA. Together these data demonstrate that exercise training improves Nrf2 signaling and downstream gene expression and that lower basal Nrf2 levels are associated with a more dynamic acute response. Our results provide evidence that the impaired Nrf2 signaling in sedentary older adults can be restored to a degree with moderate exercise training, albeit not to the level seen in young. CLINICALTRIALS.GOV ID: NCT03419988.