The Influence of COVID-19 on Patient Mobilization and Injury Attributes in the ICU: A Retrospective Analysis of a Level II Trauma Center.

The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of trauma patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n = 378) and after (n = 499) 1 April 2020 when Georgia's COVID-19 shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after-COVID patients examined the extent to which mobilization (n = 328) or lack of mobilization (n = 171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. The after-COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before-COVID patients. After-COVID patients also had a greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or days to mobilization. Within the after-COVID cohort, those who were mobilized were older, had greater Glasgow Coma Scale scores, had longer total hospital days, and had a lesser mortality rate, and a higher proportion were female. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.

Tibial bone strength is negatively affected by volumetric muscle loss injury to the adjacent muscle in male mice.

This study's objective was to investigate how contractile strength loss associated with a volumetric muscle loss (VML) injury affects the adjacent tibial bone structural and functional properties in male C57BL/6J mice. Mice were randomized into one of two experimental groups: VML-injured mice that were injured at age 12 weeks and aged to 20 weeks (8 weeks postinjury, VML) and 20-week-old age-matched uninjured mice (Uninjured-20). Tibial bone strength, mid-diaphysis cortical geometry, intrinsic material properties, and metaphyseal trabecular bone structure were assessed by three-point bending and microcomputed tomography (µCT). The plantar flexor muscle group (gastrocnemius, soleus, plantaris) was analyzed for its functional capacities, that is, peak-isometric torque and peak-isokinetic power. VML-injured limbs had 25% less peak-isometric torque and 31% less peak-isokinetic power compared to those of Uninjured-20 mice (p < 0.001). Ultimate load, but not stiffness, was significantly less (10%) in tibias of VML-injured limbs compared to those from Uninjured-20 (p = 0.014). µCT analyses showed cortical bone thickness was 6% less in tibias of VML-injured limbs compared to Uninjured-20 (p = 0.001). Importantly, tibial bone cross-section moment of inertia, the primary determinant of bone ultimate load, was 16% smaller in bones of VML-injured limbs compared to bones from Uninjured-20 (p = 0.046). Metaphyseal trabecular bone structure was also altered up to 23% in tibias of VML-injured limbs (p < 0.010). These changes in tibial bone structure and function after a VML injury occur during a natural maturation phase between the age of 12 and 20 weeks, as evidenced by Uninjured-20 mice having greater tibial bone size and strength compared to uninjured-aged 12-week mice.

Persistent altered knee loading in patients with meniscectomy: A systematic review and meta-analysis.

OBJECTIVES: To determine the changes in knee flexion moment (KFM) and knee adduction moment (KAM) during weight-bearing activities following meniscectomy. DESIGN: Meta-Analysis. SETTING: Laboratory. PARTICIPANTS: 332 meniscectomy patients and 137 healthy controls (from 13 qualified studies) MAIN OUTCOME MEASURES: Cohen's d effect sizes (ESs) were calculated to compare KAM and KFM values of the surgical legs to the non-surgical and to healthy control legs. RESULTS: When compared to healthy controls, meniscectomy patients' surgical legs demonstrated a significantly greater KAM (ES = 0.310; P = 0.002) but no significant difference in KFM (ES = -0.182; P = 0.051). When compared to the patients' non-surgical legs, however, the surgical legs showed no difference in KAM (ES = -0.024; P = 0.716) but a significantly lower KFM (ES = -0.422; P < 0.001). High heterogeneity among study ESs was observed in patients' between-limb comparison for KAM (Q-value = 20.08, P = 0.005; I2 = 65.1%) and KFM (Q-value = 43.96, P < 0.001; I2 = 79.5%). However, no significant differences in study ESs (all P > 0.102) of KFM and KAM were identified when comparing studies with various times post-surgery, weight-bearing tasks, walking speeds, or patient demographics. CONCLUSION: Elevated KAM and reduced/asymmetrical KFM observed in meniscectomy patients may contribute to the increased risk of knee OA. Rehabilitation should focus on movement education to restore between-limb KFM symmetry and reduce KAM bilaterally post-meniscectomy.

Can exercise interventions reduce external knee adduction moment during gait? A systematic review and meta-analysis.

BACKGROUND: An increased external knee adduction moment has been identified as a factor contributing to the progression of medial knee osteoarthritis. Interventions that reduce knee adduction moment may help prevent knee osteoarthritis onset and progression. While exercise interventions have been commonly used to treat knee osteoarthritis, whether exercises can modulate knee adduction moment in knee osteoarthritis patients remains unknown. This systematic review and meta-analysis aimed to determine if exercise interventions are effective in reducing knee adduction moment during gait. METHODS: Study reports published through May 2023 were screened for pre-specified inclusion/exclusion criteria. Nine studies met the eligibility criteria and yielded 24 effect sizes comparing the reduction in knee adduction moment of the exercise intervention groups to the control groups. Moderator/experimental variables concerning characteristics of the exercise interventions and included subjects (e.g., sex, BMI, type of exercise, muscle group targeted, training volume, physical therapist supervision) that may contribute to variation among studies were explored through subgroup analysis and meta-regression. FINDINGS: The effect of exercise intervention on modulating knee adduction moment during gait was no better than control (ES = -0.004, P = 0.946). Sub-group analysis revealed that the effect sizes of studies containing only females (positive exercise effect) were significantly greater than studies containing both males and females. INTERPRETATION: Exercise may not be effective in reducing knee adduction moment during gait. Clinicians aiming to decrease knee adduction moment in patients with medial knee osteoarthritis should consider alternative treatment options. Exploring the underlying mechanism(s) regarding a more positive response to exercises in females may help design more effective exercise interventions.

In vivo potentiation of muscle torque is enhanced in female mice through estradiol-estrogen receptor signaling.

Estradiol affects several properties of skeletal muscle in females including strength. Here, we developed an approach to measure in vivo posttetanic twitch potentiation (PTP) of the anterior crural muscles of anesthetized mice and tested the hypothesis that 17ß-estradiol (E2) enhances PTP through estrogen receptor (ER) signaling. Peak torques of potentiated twitches were ∼40%-60% greater than those of unpotentiated twitches and such PTP was greater in ovary-intact mice, or ovariectomized (Ovx) mice treated with E2, compared with Ovx mice (P ≤ 0.047). PTP did not differ between mice with and without ERα ablated in skeletal muscle fibers (P = 0.347). Treatment of ovary-intact and Ovx mice with ERß antagonist and agonist (PHTPP and DPN, respectively) did not affect PTP (P ≥ 0.258). Treatment with G1, an agonist of the G protein-coupled estrogen receptor (GPER), significantly increased PTP in Ovx mice from 41 ± 10% to 66 ± 21% (means ± SD; P = 0.034). Collectively, these data indicate that E2 signals through GPER, and not ERα or ERß, in skeletal muscles of female mice to augment an in vivo parameter of strength, namely, PTP.NEW & NOTEWORTHY A novel in vivo approach was developed to measure potentiation of skeletal muscle torque in female mice and highlight another parameter of strength that is impacted by estradiol. The enhancement of PTP by estradiol is mediated distinctively through the G-protein estrogen receptor, GPER.

Time, graft, sex, geographic location, and isokinetic speed influence the degree of quadriceps weakness after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: Although quadriceps weakness after ACL reconstruction (ACLR) is well documented, the magnitude of reported weakness varies considerably. Such variation raises the possibility that certain patients may be more susceptible to quadriceps weakness after ACLR. This meta-analysis identified factors explaining between-study variability in quadriceps weakness post-ACLR. METHODS: Studies between 2010 and 2020 were screened for the following criteria: human subjects, unilateral ACLR, and strength reported both for the ACLR leg and the uninjured or healthy-control leg. 122 studies met the criteria, resulting in 303 and 152 Cohen's d effect sizes (ESs) comparing ACLR legs to uninjured legs (a total of 4135 ACLR subjects) and to healthy controls (a total of 1,507 ACLR subjects vs. 1-193 healthy controls), respectively. Factors (time, graft, sex, activity, mass/height, geographic area, concomitant injury, and type of strength testing) that may affect study ES were examined. RESULTS: Meta-regressions indicated an association between time post-ACLR and study ESs (P < 0.001) and predicted full recovery (ES = 0) to occur at 54-59 months post-ACLR. When compared to uninjured legs, patients with patellar tendon autografts had greater deficits than studies using hamstring tendon autografts (P = 0.023). When compared to uninjured legs, studies including only males reported greater deficits than studies combining males and females (P = 0.045); whereas when compared to healthy controls, studies combining males and females reported greater deficits than studies with males (P = 0.013). When compared to controls, studies from USA reported greater deficits than studies from Europe (P = 0.003). Increased isokinetic-testing speed was associated with smaller deficits (P ≤ 0.025). Less than 25% of patients achieved a between-limb symmetry in quadriceps strength > 90% between 6 and 12 months post-ACLR. CONCLUSION: Time post-surgery, graft, sex, geographic location, and isokinetic speed influenced the magnitude of post-ACLR quadriceps weakness. Patients with patellar tendon autografts demonstrated greater between-limb asymmetry in quadriceps strength, while female strength deficits were underestimated to a greater extent. A slower isokinetic speed provided a more sensitive assessment of quadriceps strength post-ACLR. The overwhelming majority of patients were returning to sport with significantly impaired quadriceps strength. LEVEL OF EVIDENCE: III.

Contraction-Induced Loss of Plasmalemmal Electrophysiological Function Is Dependent on the Dystrophin Glycoprotein Complex.

Weakness and atrophy are key features of Duchenne muscular dystrophy (DMD). Dystrophin is one of the many proteins within the dystrophin glycoprotein complex (DGC) that maintains plasmalemmal integrity and cellular homeostasis. The dystrophin-deficient mdx mouse is also predisposed to weakness, particularly when subjected to eccentric (ECC) contractions due to electrophysiological dysfunction of the plasmalemma. Here, we determined if maintenance of plasmalemmal excitability during and after a bout of ECC contractions is dependent on intact and functional DGCs rather than, solely, dystrophin expression. Wild-type (WT) and dystrophic mice (mdx, mL172H and Sgcb-/- mimicking Duchenne, Becker and Limb-girdle Type 2E muscular dystrophies, respectively) with varying levels of dystrophin and DGC functionality performed 50 maximal ECC contractions with simultaneous torque and electromyographic measurements (M-wave root-mean-square, M-wave RMS). ECC contractions caused all mouse lines to lose torque (p<0.001); however, deficits were greater in dystrophic mouse lines compared to WT mice (p<0.001). Loss of ECC torque did not correspond to a reduction in M-wave RMS in WT mice (p=0.080), while deficits in M-wave RMS exceeded 50% in all dystrophic mouse lines (p≤0.007). Moreover, reductions in ECC torque and M-wave RMS were greater in mdx mice compared to mL172H mice (p≤0.042). No differences were observed between mdx and Sgcb-/- mice (p≥0.337). Regression analysis revealed ≥98% of the variance in ECC torque loss could be explained by the variance in M-wave RMS in dystrophic mouse lines (p<0.001) but not within WT mice (R 2=0.211; p=0.155). By comparing mouse lines that had varying amounts and functionality of dystrophin and other DGC proteins, we observed that (1) when all DGCs are intact, plasmalemmal action potential generation and conduction is maintained, (2) deficiency of the DGC protein ß-sarcoglycan is as disruptive to plasmalemmal excitability as is dystrophin deficiency and, (3) some functionally intact DGCs are better than none. Our results highlight the significant role of the DGC plays in maintaining plasmalemmal excitability and that a collective synergism (via each DGC protein) is required for this complex to function properly during ECC contractions.

Voluntary and magnetically evoked muscle contraction protocol in males with Duchenne muscular dystrophy: Safety, feasibility, reliability, and validity.

INTRODUCTION/AIMS: Clinical trials addressing treatments for Duchenne muscular dystrophy (DMD) require reliable and valid measurement of muscle contractile function across all disease severity levels. In this work we aimed to evaluate a protocol combining voluntary and evoked contractions to measure strength and excitability of wrist extensor muscles for safety, feasibility, reliability, and discriminant validity between males with DMD and controls. METHODS: Wrist extensor muscle strength and excitability were assessed in males with DMD (N = 10; mean ± standard deviation: 15.4 ± 5.9 years of age), using the Brooke Upper Extremity Rating Scale (scored 1-6), and age-matched healthy male controls (N = 15; 15.5 ± 5.0 years of age). Torque and electromyographic (EMG) measurements were analyzed under maximum voluntary and stimulated conditions at two visits. RESULTS: A protocol of multiple maximal voluntary contractions (MVCs) and evoked twitch contractions was feasible and safe, with 96% of the participants completing the protocol and having a less than 7% strength decrement on either measure for both DMD patients and controls (P ≥ .074). Reliability was excellent for voluntary and evoked measurements of torque and EMG (intraclass correlation coefficient [ICC] over 0.90 and over 0.85 within and between visits, respectively). Torque, EMG, and timing of twitch-onset measurements discriminated between DMD and controls (P < .001). Twitch contraction time did not differ significantly between groups (P = .10). DISCUSSION: Findings from this study show that the protocol is a safe, feasible, reliable, and a valid method to measure strength and excitability of wrist extensors in males with DMD.

Nanofiber-Based Delivery of Bioactive Lipids Promotes Pro-regenerative Inflammation and Enhances Muscle Fiber Growth After Volumetric Muscle Loss.

Volumetric muscle loss (VML) injuries after extremity trauma results in an important clinical challenge often associated with impaired healing, significant fibrosis, and long-term pain and functional deficits. While acute muscle injuries typically display a remarkable capacity for regeneration, critically sized VML defects present a dysregulated immune microenvironment which overwhelms innate repair mechanisms leading to chronic inflammation and pro-fibrotic signaling. In this series of studies, we developed an immunomodulatory biomaterial therapy to locally modulate the sphingosine-1-phosphate (S1P) signaling axis and resolve the persistent pro-inflammatory injury niche plaguing a critically sized VML defect. Multiparameter pseudo-temporal 2D projections of single cell cytometry data revealed subtle distinctions in the altered dynamics of specific immune subpopulations infiltrating the defect that were critical to muscle regeneration. We show that S1P receptor modulation via nanofiber delivery of Fingolimod (FTY720) was characterized by increased numbers of pro-regenerative immune subsets and coincided with an enriched pool of muscle stem cells (MuSCs) within the injured tissue. This FTY720-induced priming of the local injury milieu resulted in increased myofiber diameter and alignment across the defect space followed by enhanced revascularization and reinnervation of the injured muscle. These findings indicate that localized modulation of S1P receptor signaling via nanofiber scaffolds, which resemble the native extracellular matrix ablated upon injury, provides great potential as an immunotherapy for bolstering endogenous mechanisms of regeneration following VML injury.

Tissue selective effects of bazedoxifene on the musculoskeletal system in female mice.

The actions of selective estrogen receptor modulators are tissue dependent. The primary objective of the current study was to determine the tissue selective effects of bazedoxifene (BZA) on the musculoskeletal system of ovariectomized (OVX) female mice, focusing on the strengths of muscle-bone pairs in the lower hindlimb. Treatment with BZA after ovariectomy (OVX+BZA) did not prevent body or fat mass gains (P < 0.05). In vivo plantarflexor muscle isometric torque was not affected by treatment with BZA (P = 0.522). Soleus muscle peak isometric, concentric and eccentric tetanic force production were greater in OVX+BZA mice compared to OVX+E2 mice (P ≤ 0.048) with no effect on maximal isometric specific force (P = 0.228). Tibia from OVX+BZA mice had greater cortical cross-sectional area and moment of inertia than OVX mice treated with placebo (P < 0.001), but there was no impact of BZA treatment on cortical bone mineral density, cortical thickness, tibial bone ultimate load or stiffness (P ≥ 0.086). Overall, these results indicate that BZA may be an estrogen receptor agonist in skeletal muscle, as it has previously been shown in bone, providing minor benefits to the musculoskeletal system.

Downhill Running Impairs Activation and Strength of the Elbow Flexors.

ABSTRACT: Brandenberger, KJ, Warren, GL, Ingalls, CP, Otis, JS, and Doyle, JA. Downhill running impairs activation and strength of the elbow flexors. J Strength Cond Res 35(8): 2145-2150, 2021-The purpose of this study was to determine if knee extensor injury induced by 1 hour of downhill running attenuated force production in the elbow flexors. Subjects completed either downhill running for 1 hour (injured group; n = 6) or sedentary behavior (control group; n = 6). Strength and voluntary activation (%VA) were measured by isometric twitch interpolation of the elbow flexor and knee extensor muscles at the following time points in relation to the injury: before injury (Pre), after injury (Post), 24 hours after injury (24Post), and 48 hours after injury (48Post). Mean (±SE) knee extensor strength was significantly reduced (53.5 ± 9.9%) Post and remained reduced at 24Post and 48Post in the injury group. Knee extensor muscle twitch strength was reduced Post and 24Post after the downhill run (p < 0.022). Elbow flexor muscle strength was significantly reduced Post (13.2 ± 3.9%) and 24Post (17.3 ± 4.0%). Elbow flexor muscle twitch strength was not significantly different at any time point. Elbow flexor muscle %VA was not significantly reduced compared with Pre, at Post (16.2 ± 5.1%), 24Post (20.9 ± 6.7%), or 48Post (12.9 ± 4.5%). A 1-hour downhill run significantly injured the knee extensors. The elbow flexor muscles remained uninjured, but strength of these muscles was impaired by reduced %VA. These data suggest muscle injury can lead to prolonged strength deficits in muscles distant from the injury and should be accounted for when scheduling training that may lead to delayed-onset muscle soreness.

A retrospective analysis of associations between BMI and days spent on mechanical ventilation in a level 1 trauma facility.

OBJECTIVE: To examine whether BMI impacts the outcomes of mechanically ventilated patients. METHODS: Data was collected retrospectively among patients involved in motor vehicle accidents in intensive care at a major trauma center in Atlanta, GA. Patients were categorized into five BMI groups: underweight (BMI < 18.5), normal weight (BMI of 18.5-24.9), overweight (BMI of 25-29.9), obese (BMI of 30-39.9), and morbidly obese (BMI of >40). RESULTS: Among all patients (n=2,802), 3% of patients were underweight, 34% were of normal weight, 30% were overweight, 27% were obese, and 6% were morbidly obese. The mean number of ventilator days for normal weight patients was 4.6, whereas the mean number of ventilator days for underweight and morbidly obese patients were higher (10.3 and 7.4, respectively). CONCLUSIONS: Underweight and morbidly obese populations may require additional interventions during their ICU stays to address the challenges presented by having an unhealthy BMI.

Male mice with elevated C-type natriuretic peptide-dependent guanylyl cyclase-B activity have increased osteoblasts, bone mass and bone strength.

C-type natriuretic peptide (CNP) activation of guanylyl cyclase (GC)-B, also known as NPR2, stimulates cGMP synthesis and bone elongation. CNP activation requires the phosphorylation of multiple GC-B residues and dephosphorylation inactivates the receptor. GC-B7E/7E knockin mice, expressing a glutamate-substituted, "pseudophosphorylated," form of GC-B, exhibit increased CNP-dependent GC activity. Since mutations that constitutively activate GC-B in the absence of CNP result in low bone mineral density in humans, we determined the skeletal phenotype of 9-week old male GC-B7E/7E mice. Unexpectedly, GC-B7E/7E mice have significantly greater tibial and L5 vertebral trabecular bone volume fraction, tibial trabecular number, and tibial bone mineral density. Cortical cross-sectional area, cortical thickness, periosteal diameter and cortical cross-sectional moment of inertia were also significantly increased in GC-B7E/7E tibiae. Three-point bending measurements demonstrated that the mutant tibias and femurs had greater ultimate load, stiffness, energy to ultimate load, and energy to failure. No differences in microhardness indicated similar bone quality at the tissue level between the mutant and wildtype bones. Procollagen 1 N-terminal propeptide and osteocalcin were elevated in serum, and osteoblast number per bone perimeter and osteoid width per bone perimeter were elevated in tibias from the mutant mice. In contrast to mutations that constitutively activate GC-B, we report that mutations that enhance GC-B activity only in the presence of its natural ligand, increase bone mass, bone strength, and the number of active osteoblasts at the bone surface.

Plasmalemma Function Is Rapidly Restored in Mdx Muscle after Eccentric Contractions.

PURPOSE: Muscle that lacks dystrophin, as in the mdx mouse, has a heightened sensitivity to eccentric (ECC) contraction-induced strength loss but an enhanced rate of recovery. However, the timeline and mechanisms underlying why mdx muscle recovers quicker have yet to be determined. We used an EMG approach to analyze plasmalemma electrophysiological function during and after ECC contraction-induced injury to test the hypothesis that loss of plasmalemmal excitability is a transient event in mdx muscle. METHODS: Mice were implanted with stimulating electrodes on the common peroneal nerve and EMG electrodes on the tibialis anterior muscle. Anterior crural muscles of anesthetized mice performed one or two bouts of 50 injurious ECC contractions, and recovery of maximal isometric torque and M-wave root mean square (RMS) were assessed after each bout. RESULTS: Maximal isometric torque and M-wave RMS were equally reduced 62% (P < 0.001) in mdx mice immediately after the initial ECC injury. For these mdx mice, M-wave RMS was still reduced at 2 d postinjury (P = 0.034) but was not different from preinjury values by 6 d (P = 0.106), whereas torque took up to 9 d to recover (P = 0.333). M-wave RMS did not change (P = 0.390) in wild-type mice in response to ECC injury, whereas torque decreased 35% (P < 0.001) and recovered by day 2 (P = 0.311). Results from the second bout of ECC contractions were similar to those observed during and after the initial injury. CONCLUSION: Functional dystrophin is necessary for excitation to occur at the plasmalemma during ECC contractions but is not essential for the complete recovery of plasmalemma electrophysiological function or maximal isometric strength.

Therapeutic Approaches for Volumetric Muscle Loss Injury: A Systematic Review and Meta-Analysis.

Our goal was to understand the impact of regenerative therapies on the functional capacity of skeletal muscle following volumetric muscle loss (VML) injury. An extensive database search (e.g., PubMed, Cochrane Library, and ClinicalTrials.gov) was conducted up through January 2019 to evaluate the following: "In humans or animals with VML injury, is treatment better than no treatment at recovering functional capacity?" Study eligibility criteria required studies to have both an untreated and at least one treated VML injury group. From 2312 study reports, 44 studies met the inclusion criteria. Quantitative functional capacity data (absolute and/or normalized strength) or proportional measures (histological analysis quantifying viable muscle tissue, mitochondrial function, and/or exhaustive treadmill running) were extracted for use. While both human and animal studies were included in the searches, only animal studies met the eligibility criteria. Using a random-effects model, Hedges' g was used as the effect size (ES) and calculated such that a positive ES indicated treatment efficacy. The overall ES was 0.75 (95% confidence interval: 0.53-0.96; p < 0.0000001), indicating that the treatments, on average, resulted in a significant improvement in functional capacity. From network meta-analyses, it was determined that an acellular biomaterial combined with stem and/or progenitor cells had the greatest treatment effectiveness. The findings indicate that various treatments in animal models of VML improve the functional capacity of muscle compared to leaving the injury untreated; however, the ∼16% beneficial effect is small. Our results suggest that current regenerative therapy paradigms require further maturation to achieve clinically meaningful improvements in the functional capacity of the muscle. Impact Statement Our most salient findings are that (1) various treatment approaches used in animal models of volumetric muscle loss (VML) injury improve functional capacity compared to leaving the injury untreated and (2) an acellular biomaterial in combination with cellular components was the most effective treatment to improve functional capacity following VML injury to date. The nature of our findings has substantial implications for regenerative medicine, biomedical engineering, and rehabilitative techniques currently being evaluated and developed for VML injury repair, and are pivotal to the progression of the regenerative medicine effort aimed at restoring maximal function to traumatized and disabled limbs.

Caffeine Ingestion With or Without Low-Dose Carbohydrate Improves Exercise Tolerance in Sedentary Adults.

Caffeine (CAF) and carbohydrate (CHO) ingestion delay fatigue during prolonged exercise; however, this is primarily documented in endurance trained (ET) athletes. Our purpose was to determine if these ergogenic aids are also effective to improve exercise tolerance in age-matched sedentary (SED) adults. Using a double-blind crossover design, ET and SED (n = 12 each group) completed four exercise trials consisting of 30 min cycling at standardized matched work rates 10% below lactate threshold (MOD-EX) followed by a time to fatigue (TTF) ride at individually prescribed intensity of 5% above lactate threshold. After standardized breakfast, the following drink treatments were given before and throughout exercise: CAF (3 mg/kg of body mass, equivalent to 1.5 cups premium brewed coffee), low calorie CHO (LCHO) (0.4% solution, 2 g total CHO), CAF+LCHO, and artificially-sweetened placebo (PLA). SED and ET had similar perceived exertion (RPE) during MOD-EX and TTF (23.8 ± 3.1 and 24.1 ± 2.6 min in ET, SED, respectively). LCHO did not benefit exercise tolerance compared to PLA and was less effective (p < 0.05) compared to CAF+LCHO for all participants combined. Thus, the two CAF treatments were averaged, resulting in ~5% lower RPE (p < 0.05) and 21% longer TTF (26.3 ± 10.4 min) compared to the no-CAF (21.7 ± 9.9 min) treatments. Blood glucose and lactate were higher (p < 0.05) with CAF vs. no-CAF. SED and ET only differed in metabolic oxidation rates during exercise (higher overall fat oxidation with ET compared to SED). CAF reduces the perceived effort during exercise and increases the capacity for sedentary individuals, as well as trained athletes, to tolerate higher intensity exercise for greater duration; and, these benefits were not further enhanced by ingesting doses of low carbohydrate regularly during exercise.

Acromion morphology and prevalence of rotator cuff tear: A systematic review and meta-analysis.

The causes of degenerative rotator cuff (RTC) tears are unclear but certain acromion morphology may contribute. This study's objective was to determine using a systematic review and meta-analysis the association of acromion type and acromial index with the prevalence of RTC tears. Six databases were searched electronically. Seventeen relevant studies between 1993 and 2017 were included in the meta-analyses determining the association of RTC tears with acromion type (n = 11) or acromial index (n = 10). Effect sizes were calculated as an odds ratio (OR) for the studies reporting acromion type and as raw mean difference (RMD) for the studies reporting acromial index. Meta-analysis was performed using a random-effects model. There was a significant small-to-medium effect found in the meta-analysis for acromion type (overall OR = 2.82, P = 0.000003), indicating an almost three times greater odds for a RTC tear in individuals with a type-III acromion as compared with those with a type-I or -II. A significant effect was also found for acromial index (RMD = 0.071, P < 0.0000001), indicating that a larger acromial index is associated with a greater likelihood of a RTC tear. Because of substantial heterogeneity in RMD for acromial index (Q-df = 92, P < 0.00001; I2 = 89%), subgroup analyses and meta-regressions were performed. Interestingly, the continent where the study was conducted (i.e., Europe vs. Asia) was the only moderator variable that could explain some of the acromial index heterogeneity. Overall, the findings from our analyses indicate that individuals with either a type-III acromion and/or a larger acromial index have a greater likelihood for non-traumatic RTC tears. Clin. Anat. 32:122-130, 2019. © 2018 Wiley Periodicals, Inc.

A moderate oestradiol level enhances neutrophil number and activity in muscle after traumatic injury but strength recovery is accelerated.

KEY POINTS: The female hormone oestrogen may protect muscle from injury by reducing inflammation but this is debatable. In this study, the inflammatory response of injured muscle from oestrogen-replete mice was comprehensively compared to that from oestrogen-deficient mice. We show that oestrogen markedly promotes movement of neutrophils, an inflammatory white blood cell type, into muscle over the first few days after injury but has only a minor effect on the movement of macrophages, another inflammatory cell type. Despite the enhancement of inflammation by oestrogen in injured muscle, we found strength in oestrogen-replete mice to recover faster and to a greater extent than it does in oestrogen-deficient mice. Our study and others indicate that lower doses of oestrogen, such as that used in our study, may affect muscle inflammation and injury differently from higher doses. ABSTRACT: Oestrogen has been shown to protect against skeletal muscle injury and a reduced inflammatory response has been suggested as a possible protective mechanism. There are, however, dissenting reports. Our objective was to conduct an unbiased, comprehensive study of the effect of oestradiol on the inflammatory response following muscle injury. Female C57BL6/J mice were ovariectomized and supplemented with and without oestradiol. Tibialis anterior muscles were freeze injured and studied primarily at 1-4 days post-injury. Oestradiol supplementation increased injured muscle gene expression of neutrophil chemoattractants (Cxcl1 and Cxcl5) and to a lesser extent that of monocyte/macrophage chemoattractants (Ccl2 and Spp1). Oestradiol markedly increased gene expression of the neutrophil cell surface marker (Ly6g) but had less consistent effects on the monocyte/macrophage cell surface markers (Cd68, Cd163 and Cd206). These results were confirmed at the protein level by immunoblot with oestradiol increasing LY6G/C content and having no significant effect on CD163 content. These findings were confirmed with fluorescence-activated cell sorting counts of neutrophils and macrophages in injured muscles; oestradiol increased the proportion of CD45+ cells that were neutrophils (LY6G+ ) but not the proportion that were macrophages (CD68+ or CD206+ ). Physiological impact of the oestradiol-enhanced neutrophil response was assessed by strength measurements. There was no significant difference in strength between oestradiol-supplemented and -unsupplemented mice until 2 weeks post-injury; strength was 13-24% greater in supplemented mice at 2-6 weeks post-injury. In conclusion, a moderate level of oestradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery.

Early rehabilitation for volumetric muscle loss injury augments endogenous regenerative aspects of muscle strength and oxidative capacity.

BACKGROUND: Volumetric muscle loss (VML) injuries occur due to orthopaedic trauma or the surgical removal of skeletal muscle and result in debilitating long-term functional deficits. Current treatment strategies do not promote significant restoration of function; additionally appropriate evidenced-based practice physical therapy paradigms have yet to be established. The objective of this study was to develop and evaluate early rehabilitation paradigms of passive range of motion and electrical stimulation in isolation or combination to understand the genetic and functional response in the tissue remaining after a multi-muscle VML injury. METHODS: Adult male mice underwent an ~ 20% multi-muscle VML injury to the posterior compartment (gastrocnemius, soleus, and plantaris muscle) unilaterally and were randomized to rehabilitation paradigm twice per week beginning 2 days post-injury or no treatment. RESULTS: The most salient findings of this work are: 1) that the remaining muscle tissue after VML injury was adaptable in terms of improved muscle strength and mitigation of stiffness; but 2) not adaptable to improvements in metabolic capacity. Furthermore, biochemical (i.e., collagen content) and gene (i.e., gene arrays) assays suggest that functional adaptations may reflect changes in the biomechanical properties of the remaining tissue due to the cellular deposition of non-contractile tissue in the void left by the VML injury and/or differentiation of gene expression with early rehabilitation. CONCLUSIONS: Collectively this work provides evidence of genetic and functional plasticity in the remaining skeletal muscle with early rehabilitation approaches, which may facilitate future evidenced-based practice of early rehabilitation at the clinical level.

Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis.

BACKGROUND: There is debate as to whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is beneficial after acute skeletal muscle injury. Some studies have suggested that NSAID use may be detrimental to injured muscle. PURPOSE: To determine whether NSAID use affects recovery from skeletal muscle injury as assessed by strength loss, soreness, and/or blood creatine kinase level. STUDY DESIGN: Systematic review and meta-analysis. METHODS: An extensive systematic review was completed searching 16 databases (eg, PubMed, Cochrane Library, EMBASE). Inclusion criteria were (1) acute injury to skeletal muscle, (2) use of a control condition, (3) certainty of the NSAID dose administered, and (4) use of 1 or more of the 3 desired outcome measures. A total of 5343 study reports were screened, of which 41 studies were deemed suitable for inclusion. The standardized mean difference was used as the effect size (ES) and was calculated such that a positive ES indicated NSAID efficacy. Meta-analyses were run using a random-effects model. RESULTS: For all studies, time points after injury, and injury markers combined, NSAID use was found to elicit a small to medium, significant decrease in the markers of injury (overall ES = +0.34; P = .0001). Because heterogeneity in study ES was apparent (ie, Q- df = 52.4, P = .000005; I2 = 57%), subgroup meta-analyses and meta-regressions were run in an attempt to explain the heterogeneity. In human studies, study ESs were higher when lower body muscles were injured ( P = .045). In animal studies, study ESs were lower with longer NSAID administration durations ( P = .023) and at longer follow-up times after injury ( P = .010). CONCLUSION: Overall, our analysis supports NSAID use for reducing strength loss, soreness, and blood creatine kinase level after an acute muscle injury, at least for humans and in the short term. Additional research is required to determine why NSAID use appears to be more effective when lower-body muscles in humans are injured. It would also be important to determine why NSAID use appears detrimental at later times after injury in animals but not humans.