Manual therapy and exercise effects on inflammatory cytokines: a narrative overview.

Background: Matching disease and treatment mechanisms is a goal of the Precision Medicine Initiative. Pro- and anti-inflammatory cytokines (e.g., Tumor Necrosis Factor-alpha, Transforming Growth Factor-beta, and Interleukin-2, 10, and 12) have gained a significant amount of interest in their potential role in persistent pain for musculoskeletal (MSK) conditions. Manual therapy (MT) and exercise are two guideline-recommended approaches for treating MSK conditions. The objective of this narrative overview was to investigate of the effects of MT and exercise on pro- and anti-inflammatory cytokines and determine the factors that lead to variability in results. Methods: Two reviewers evaluated the direction and variabilities of MT and exercise literature. A red, yellow, and green light scoring system was used to define consistencies. Results: Consistencies in responses were seen with acute and chronic exercise and both pro- and anti-inflammatory cytokines. Chronic exercise is associated with a consistent shift towards a more anti-inflammatory cytokine profile (Transforming Growth Factor-beta, and Interleukin-2 and 13, whereas acute bouts of intense exercise can transiently increase pro-inflammatory cytokine levels. The influence of MT on cytokines was less commonly studied and yielded more variable results. Conclusion: Variability in findings is likely related to the subject and their baseline condition or disease, when measurement occurs, and the exercise intensity, duration, and an individual's overall health and fitness.

The Surgical Management of NCAA Division 1 College Football Injuries Post COVID-19: A Single Institution Retrospective Review.

ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.

One episode of low intensity aerobic exercise prior to systemic AAV9 administration augments transgene delivery to the heart and skeletal muscle.

INTRODUCTION: The promising potential of adeno-associated virus (AAV) gene delivery strategies to treat genetic disorders continues to grow with an additional three AAV-based therapies recently approved by the Food and Drug Administration and dozens of others currently under evaluation in clinical trials. With these developments, it has become increasingly apparent that the high doses currently needed for efficacy carry risks of toxicity and entail enormous manufacturing costs, especially for clinical grade products. Strategies to increase the therapeutic efficacy of AAV-mediated gene delivery and reduce the minimal effective dose would have a substantial impact on this field. We hypothesized that an exercise-induced redistribution of tissue perfusion in the body to favor specific target organs via acute aerobic exercise prior to systemic intravenous (IV) AAV administration could increase efficacy. BACKGROUND: Aerobic exercise triggers an array of downstream physiological effects including increased perfusion of heart and skeletal muscle, which we expected could enhance AAV transduction. Prior preclinical studies have shown promising results for a gene therapy approach to treat Barth syndrome (BTHS), a rare monogenic cardioskeletal myopathy, and clinical studies have shown the benefit of low intensity exercise in these patients, making this a suitable disease in which to test the ability of aerobic exercise to enhance AAV transduction. METHODS: Wild-type (WT) and BTHS mice were either systemically administered AAV9 or completed one episode of low intensity treadmill exercise immediately prior to systemic administration of AAV9. RESULTS: We demonstrate that a single episode of acute low intensity aerobic exercise immediately prior to IV AAV9 administration improves marker transgene delivery in WT mice as compared to mice injected without the exercise pre-treatment. In BTHS mice, prior exercise improved transgene delivery and additionally increased improvement in mitochondrial gene transcription levels and mitochondrial function in the heart and gastrocnemius muscles as compared to mice treated without exercise. CONCLUSIONS: Our findings suggest that one episode of acute low intensity aerobic exercise improves AAV9 transduction of heart and skeletal muscle. This low-risk, cost effective intervention could be implemented in clinical trials of individuals with inherited cardioskeletal disease as a potential means of improving patient safety for human gene therapy.

Elevated liver glycogenolysis mediates higher blood glucose during acute exercise in Barth syndrome.

Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defects in muscle mitochondrial oxidative metabolism result in an enhanced reliance on anaerobic metabolism during exercise to meet energy demands of muscular work. During exercise, the liver normally increases glucose production via glycogenolysis and gluconeogenesis to match the elevated rate of muscle glucose uptake and meet the ATP requirements of working muscle. However, the impact of Tafazzin deficiency on hepatic glucose production and the pathways contributing to hepatic glucose production during exercise is unknown. Therefore, the purpose of this study was to quantify in vivo liver gluconeogenesis and glycogenolysis in Tafazzin knockdown mice at rest and during acute exercise. METHODS: Male TAFAZZIN shRNA transgenic (TG) and wild-type (WT) mice completed exhaustive treadmill running protocols to test exercise tolerance. Mice underwent 2H- and 13C-stable isotope infusions at rest and during a 30-minute treadmill running bout to quantify hepatic glucose production and associated nutrient fluxes under sedentary conditions and during acute exercise. Circulating and tissue (skeletal muscle and liver) samples were obtained during and following exercise to assess static metabolite levels. RESULTS: TG mice reached exhaustion sooner during exhaustive treadmill running protocols and exhibited higher plasma lactate concentrations after exhaustive exercise compared to WT mice. Arterial glucose levels were comparable between genotypes at rest, but higher in TG mice compared to WT mice during exercise. Consistent with the higher blood glucose, TG mice showed increased endogenous glucose production owing to elevated glycogenolysis compared to WT mice during exercise. Total gluconeogenesis, gluconeogenesis from glycerol, gluconeogenesis from phosphoenolpyruvate, pyruvate cycling, total cataplerosis, and anaplerotic fluxes were similar between TG and WT mice at rest and during exercise. However, lactate dehydrogenase flux and TCA cycle fluxes trended higher in TG mice during exercise. Liver glycogen content in TG was higher in TG vs. controls. CONCLUSION: Our data in the Tafazzin knockdown mouse suggest that elevated anaerobic metabolism during rest and exercise previously reported in humans with BTHS are supported by the finding of higher hepatic glycogenolysis.

A Regional Analysis of Hospital Readmissions Following Total Hip and Knee Arthroplasty and the Impact of Medicaid Expansion.

The Hospital Readmissions Reduction Program (HRRP) works to temper nationally rising readmission rates. Total knee arthroplasty (TKA) and total hip arthroplasty (THA) have a 30-day readmission cost burden of $889,300 and $689,400, respectively. No research has compared TKA and THA readmission rates by region and Medicaid expansion status. This study compares THA and TKA readmission rates in the United States by region, Medicaid status, and performance. One-way ANOVAs were conducted to determine the regions with the highest and lowest mean excess readmission ratios (ERRs). An independent t-test compared Medicaid versus non-Medicaid expansion states. Southern hospitals have the highest mean ERR, followed by northeastern, midwestern, and then western hospitals. Although Medicaid expansion states have significantly lower ERRs compared to non-expansion states, Medicaid status alone does not account for regional differences in ERRs after THA and TKA. Regional factors likely confound Medicaid status's effect on readmission rates. (Journal of Surgical Orthopaedic Advances 32(1):005-008, 2023).

Matrix produced by diseased cardiac fibroblasts affects early myotube formation and function.

The extracellular matrix (ECM) provides both physical and chemical cues that dictate cell function and contribute to muscle maintenance. Muscle cells require efficient mitochondria to satisfy their high energy demand, however, the role the ECM plays in moderating mitochondrial function is not clear. We hypothesized that the ECM produced by stromal cells with mitochondrial dysfunction (Barth syndrome, BTHS) provides cues that contribute to metabolic dysfunction independent of muscle cell health. To test this, we harnessed the ECM production capabilities of human pluripotent stem-cell-derived cardiac fibroblasts (hPSC-CFs) from healthy and BTHS patients to fabricate cell-derived matrices (CDMs) with controlled topography, though we found that matrix composition from healthy versus diseased cells influenced myotube formation independent of alignment cues. To further investigate the effects of matrix composition, we then examined the influence of healthy- and BTHS-derived CDMs on myotube formation and metabolic function. We found that BTHS CDMs induced lower fusion index, lower ATP production, lower mitochondrial membrane potential, and higher ROS generation than the healthy CDMs. These findings imply that BTHS-derived ECM alone contributes to myocyte dysfunction in otherwise healthy cells. Finally, to investigate potential mechanisms, we defined the composition of CDMs produced by hPSC-CFs from healthy and BTHS patients using mass spectrometry and identified 15 ECM and related proteins that were differentially expressed in the BTHS-CDM compared to healthy CDM. Our results highlight that ECM composition affects skeletal muscle formation and metabolic efficiency in otherwise healthy cells, and our methods to generate patient-specific CDMs are a useful tool to investigate the influence of the ECM on disease progression and to investigate variability among diseased patients. STATEMENT OF SIGNIFICANCE: Muscle function requires both efficient metabolism to generate force and structured extracellular matrix (ECM) to transmit force, and we sought to examine the interactions between metabolism and ECM when metabolic disease is present. We fabricated patient-specific cell derived matrices (CDMs) with controlled topographic features to replicate the composition of healthy and mitochondrial-diseased (Barth syndrome) ECM. We found that disease-derived ECM negatively affects metabolic function of otherwise healthy myoblasts, and we identified several proteins in disease-derived ECM that may be mediating this dysfunction. We anticipate that our patient-specific CDM system could be fabricated with other topographies and cell types to study cell functions and diseases of interest beyond mitochondrial dysfunction and, eventually, be applied toward personalized medicine.

Effect of excessive gestational weight gain on insulin sensitivity and insulin kinetics in women with overweight/obesity.

OBJECTIVE: Obesity increases the risk for pregnancy complications and maternal hyperglycemia. The Institute of Medicine developed guidelines for gestational weight gain (GWG) targets for women with overweight/obesity, but it is unclear whether exceeding these targets has adverse effects on maternal glucose metabolism. METHODS: Insulin sensitivity (assessed using the Matsuda Insulin Sensitivity Index), ß-cell function (assessed as insulin secretion rate in relation to plasma glucose), and plasma insulin clearance rate were evaluated using a frequently sampled oral glucose tolerance test at 15 and 35 weeks of gestation in 184 socioeconomically disadvantaged African American women with overweight/obesity. RESULTS: Insulin sensitivity decreased, whereas ß-cell function and insulin clearance increased from 15 to 35 weeks of gestation in the entire group. Compared with women who achieved the recommended GWG, excessive GWG was associated with a greater decrease in insulin sensitivity between 15 and 35 weeks. ß-cell function and plasma insulin clearance were not affected by excessive GWG. CONCLUSIONS: These data demonstrate that gaining more weight during pregnancy than recommended by the Institute of Medicine is associated with functional effects on glucose metabolism.

ADHD Prescription Medications and Their Effect on Athletic Performance: A Systematic Review and Meta-analysis.

BACKGROUND: Stimulant medications used for the treatment of Attention Deficit-Hyperactivity Disorder (ADHD) are believed to provide a physical advantage in athletics, but several of these medications are not regulated by the World Anti-Doping Association. Given the prevalence of ADHD among the athlete population and concern for abuse of ADHD medications, this review and meta-analysis aimed to evaluate effects of ADHD medications on athletic performance, thereby appraising the validity of claims of performance enhancement. METHODS: A search of MEDLINE, Embase, CINAHL, and Cochrane Review databases was performed for all randomized controlled trials evaluating athletic performance after ingestion of placebo or ADHD treatment medications from August 2020 through November 2020. All RCTs identified from these search criteria were included for screening, with exclusion of any animal studies. Two reviewers (JB, CK) assessed methodological quality and risk of bias using CONSORT 2010 and Cochrane Collaboration tools. Study results were compiled with corresponding p values for each finding. Effect sizes (Cohen's D) for athletic performance and physiological changes were aggregated for each study. Studies were further screened for homogeneity that would allow for meta-analysis. Heterogeneity was calculated using I2. RESULTS: A total of 13,033 abstracts evaluating amphetamine, methamphetamine, methylphenidate, and bupropion were screened. The final analysis included nine studies, six of which found significant improvement in athletic performance with use of stimulant medications (p < 0.05). Methylphenidate and amphetamine were consistently identified to have a performance effect. Secondary effects identified included significant increase in heart rate, core temperature, and elevation of various serum hormone levels (p < 0.05). Effect size evaluation found seven studies demonstrating small to large effects on physical performance, as well as in categories of cardiometabolic, temperature, hormone, and ratings of perceived exertion, to varying degrees. A meta-analysis was performed on two studies, demonstrating conflicting results. CONCLUSIONS: Dopaminergic/noradrenergic agonist medications appear to have a positive effect on athletic performance, as well as effects on physiological parameters. Further consideration of medications currently not regulated, i.e. bupropion, is warranted given evidence of athletic performance enhancement. PROSPERO trial registration number: CRD42020211062; 10/29/2020 retrospectively registered.

A Comparison of Two-Year Anterior Cruciate Ligament Reconstruction Clinical Outcomes Using All-Soft Tissue Quadriceps Tendon Autograft With Femoral/Tibial Cortical Suspensory Fixation Versus Tibial Interference Screw Fixation.

PURPOSE: To contribute to future quadriceps tendon harvest and fixation guidelines in the setting of anterior cruciate ligament reconstruction by comparing 2-year patient-reported subjective knee outcome scores and incidence of graft-related complications between the shorter harvest all-inside tibial-femoral suspensory fixation (TFSF) approach versus the longer harvest standard tibial interference screw fixation technique. METHODS: Patients who underwent primary anterior cruciate ligament reconstruction with all soft tissue quadriceps tendon autograft from January 2017 to May 2019 were identified for inclusion. Patients were matched into 2 cohorts of 62 based on reconstruction technique. All patients completed baseline and minimum 2-year International Knee Documentation Committee, Tegner Activity Level, and Lysholm questionnaires and were queried regarding subsequent procedures and complications to the operative knee. RESULTS: Average graft length for the all-inside TFSF was 69.55 (95% confidence interval 68.99-70.19) mm versus 79.27 (95% confidence interval 77.21-81.34) mm in the tibial screw fixation cohort (P = .00001). Two-year Lysholm scores were greater in the TFSF cohort (P = .04) but were not clinically significant. There was no difference in 2-year International Knee Documentation Committee (P = .09) or Tegner (P = .69) scores between cohorts, but more patients in the TFSF cohort returned to or exceeded their baseline activity level compared with the tibial screw fixation cohort (73% vs 61%, P = .25). Seven patients in the TFSF cohort versus 13 in the tibial screw fixation cohort reported anterior knee pain or kneeling difficulty (P = .22). There were no differences in reported complications. CONCLUSIONS: All-inside soft-tissue quadriceps tendon autograft with TFSF resulted in clinically comparable subjective outcome scores at 2 years to tibial screw fixation. There were also no differences in complications or reports of anterior knee pain or kneeling difficulty. All-inside TFSF can be a viable alternative to tibial screw fixation for all-soft tissue quadriceps autograft. LEVEL OF EVIDENCE: III, comparative therapeutic trial.

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

BACKGROUND: Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity. We used these measures of structural brain integrity to assess white matter changes, physical fitness, and cognition in a cross-sectional study of PLWH. METHODS: Forty-four virologically well-controlled PLWH were recruited (average age of 56 years, a median recent CD4+ count of 682 cells/mm3). Diffusion tensor imaging -derived fractional anisotropy (FA) and diffusion basis spectrum imaging-derived axonal density were calculated. Cardiorespiratory fitness [maximal volume of oxygen consumption (VO2 max)] was measured by performing indirect calorimetry during exercise to volitional exhaustion. Cardiovascular risk was assessed by the Framingham risk score. Neuropsychological performance (NP) testing evaluated learning, memory, psychomotor/processing speed, and executive function. Partial correlations assessed the relationships among cardiorespiratory fitness, neuroimaging, NP, and HIV clinical metrics (CD4+ count and time since diagnosis). RESULTS: Higher VO2 max was associated with higher FA and higher axonal density in multiple white matter tracts, including the corticospinal tract and superior longitudinal fasciculus. Better NP in the motor/psychomotor domain was positively associated with FA and axonal density in diverse tracts including those associated with motor and visuospatial processing. However, higher VO2 max was not associated with NP or HIV clinical metrics. CONCLUSIONS: An active lifestyle promoting cardiorespiratory fitness may lead to better white matter integrity and decreased susceptibility to cognitive decline in virologically well-controlled PLWH.

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.

Telehealth in an Orthopedic Sports Medicine Clinic: The First 100 Patients.

Background: Orthopedic specialties have begun to embrace telehealth as an alternative to in-person visits. We have not found studies assessing telehealth in sports medicine. Our goal is to evaluate patient perception of telehealth in an orthopedic sports medicine practice. Methods: Institutional review board (IRB) approval was obtained. The first 100 patients 18 years and older who had their initial videoconference telehealth appointment with our sports medicine providers from March to April 2020 were contacted at the conclusion of their visit. Surveys assessed satisfaction with telehealth, the provider, and whether attire played a role in their perception of the quality of the telehealth visit. Results: Patients on average stated excellent satisfaction with their visit (4.76 out of 5) and their provider (4.98 out of 5). Patients slightly disagreed with the notion that telehealth is equivalent to in-person provider visits (2.95 out of 5). This did not affect their perception to telehealth itself. It did not discourage patients from recommending telehealth or their provider to future patients. Patients overall felt that attire of the provider does not influence their opinion as to the standard of care they received. Returning patients versus new patient visits were more likely to recommend telehealth to others (4.83 vs. 4.56, p = 0.04). The responses from both groups were overwhelmingly positive. Conclusion: Telehealth is a viable clinic option in an orthopedic sports medicine clinic. Patients who have seen providers in-person previously are more likely to recommend telehealth versus new patients. New patients were satisfied with their telehealth experience. Level of Evidence:IV.

Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: a systematic review.

PURPOSE: To determine whether supplementation with turmeric or curcumin extract effects pain and physical function in individuals with knee osteoarthritis (OA). Second, we investigated the therapeutic response (pain and function) of turmeric compared with non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A search was conducted in MEDLINE, Embase, CINAHL and Cochrane Review. Inclusion criteria included randomised controlled trials reporting pain and physical function in humans with knee OA comparing turmeric therapy with NSAIDs or no therapy. Two reviewers screened 5273 abstracts. Risk of bias and quality were assessed via Cochrane Collaboration tool and CONSORT (Consolidated Standards of Reporting Trials) 2010, respectively. RESULTS: Ten studies were included in the final analysis. Eight had high methodological quality and two were categorised as good with a mean CONSORT quality score of 21.1. Nine studies had adequate sequence generation and six had adequate allocation concealment. Participants and outcome assessors were blinded in eight studies. Three of the studies compared turmeric therapy to NSAIDs. All 10 studies showed improvement in pain and function from baseline with turmeric therapy (p≤0.05). In three studies comparing turmeric to NSAIDs, there were no differences in outcome scores (p>0.05). In all studies there were no significant adverse events in the turmeric therapy group. CONCLUSION: Compared with placebo, there appears to be a benefit of turmeric on knee OA pain and function. Based on a small number of studies the effects are similar to that of NSAIDs. Variables such as optimal dosing, frequency and formulation remain unclear at this time.

Validity of the 6-Minute Walk Test and YMCA Submaximal Cycle Test During Midpregnancy.

ABSTRACT: Tinius, RA, Blankenship, M, Maples, JM, Pitts, BC, Furgal, K, Norris, ES, Hoover, DL, Olenick, A, Lambert, J, and Cade, WT. Validity of the 6-minute walk test and Young Men's Christian Association (YMCA) submaximal cycle test during midpregnancy. J Strength Cond Res 35(11): 3236-3242, 2021-Submaximal exercise testing can be a feasible alternative to maximal testing within special populations to safely predict fitness levels; however, submaximal exercise testing has not been well-validated for use during pregnancy. The purpose of this study was to determine the concurrent validity of the 6-minute walk test (6MWT) and the YMCA submaximal cycle test (YMCAT) to predict V̇o2max in physically active women during midpregnancy. Thirty-seven (n = 37) pregnant women (22.1 ± 1.4 weeks' gestation) and 10 (n = 10) nonpregnant women participated in the study. Subjects completed a graded maximal treadmill test at 1 visit to measure maximal oxygen consumption (V̇o2max), and then subjects completed the 6MWT and YMCAT in randomized order during a separate visit. The predicted V̇o2max from each submaximal test were compared with the measured V̇o2max from the treadmill test to assess the validity of these tests during pregnancy. Among pregnant women, predicted V̇o2max from the YMCAT was not correlated to the measured V̇o2max (r = 0.14, p = 0.42), and the predicted V̇o2max from the 6MWT was only moderately correlated (r = 0.40, p = 0.016) to the measured V̇o2max. Among nonpregnant women, the predicted V̇o2max values from both the YMCAT and the 6MWT had strong correlations with the measured V̇o2max values (YMCAT: r = 0.71, p = 0.02; 6MWT: r = 0.80, p = 0.006). Neither test demonstrated concurrent validity among the pregnant sample. The main finding is that the YMCAT is not a valid method to estimate V̇o2max during midpregnancy (likely due to physiological changes in heart rate [HR] during pregnancy). The 6MWT has potential to be used clinically for estimating fitness as actual and predicted values did positively correlate, and it is not dependent on HR responses to exercise. However, if a precise measure of fitness is needed, then neither test appears to have strong validity for use during midpregnancy.

A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.

INTRODUCTION: Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes. METHODS: We studied 10 sedentary men with obesity (body mass index, 33 ± 3 kg·m-2) and prediabetes by using a randomized, cross-over study design. After an overnight fast, participants completed either a single bout of whole-body RE (seven exercises, 3 sets of 10-12 repetitions at 80% one-repetition maximum each) or an equivalent period of rest. Participants subsequently completed a mixed meal test in conjunction with an intravenous [6,6-2H2]glucose infusion to determine basal and postprandial glucose rate of appearance (Ra) and disappearance (Rd) from plasma, insulin sensitivity, and the insulinogenic index (a measure of beta cell function). Skeletal muscle biopsies were obtained 90 min postmeal to evaluate pyruvate-supported and maximal mitochondrial respiration. Whole-body carbohydrate oxidation was assessed using indirect calorimetry. RESULTS: RE significantly reduced the postprandial rise in glucose Ra and plasma glucose concentration. Postprandial insulin sensitivity was significantly greater after RE, whereas postprandial plasma insulin concentration was significantly reduced. RE had no effect on the insulinogenic index, postprandial pyruvate respiration, or carbohydrate oxidation. CONCLUSION/INTERPRETATION: A single bout of RE has beneficial effects on postprandial glucose metabolism in men with obesity and prediabetes by increasing postprandial insulin sensitivity, reducing the postprandial rise in glucose Ra, and reducing postprandial plasma insulin concentration.

Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome.

BACKGROUND: Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function. METHODS/RESULTS: Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of 15O-water and 1-11C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging. LV function and cardiac high-energy phosphate metabolism were examined via echocardiography and 31P magnetic resonance spectroscopy, respectively. Myocardial glucose extraction fraction (21 ± 14% vs 10 ± 8%, P = .03) and glucose utilization (828.0 ± 470.0 vs 393.2 ± 361.0 µmol·g-1·min-1, P = .02) were significantly higher in BTHS vs Control. Myocardial FA extraction fraction (31 ± 7% vs 41 ± 6%, P < .002) and uptake (0.25 ± 0.04 vs 0.29 ± 0.03 mL·g-1·min-1, P < .002) were significantly lower in BTHS vs Control. Altered myocardial metabolism was associated with lower cardiac function in BTHS. CONCLUSIONS: Myocardial substrate metabolism is altered and may contribute to LV dysfunction in BTHS. Clinical Trials #: NCT01625663.

Supplement Use in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To assess whether a standardized dietary supplementation can help to decrease postoperative muscle atrophy and/or improve rehabilitation outcomes in patients who underwent anterior cruciate ligament reconstruction (ACLR). METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). MEDLINE, Scopus, and Cochrane Library databases were searched, and articles that examined protein or amino acid, vitamin, or any other type of supplementation in ACLR were reviewed. Two independent reviewers conducted the search using pertinent Boolean operations. RESULTS: A total of 1818 articles were found after our database search. Ten studies fulfilled our inclusion criteria and only assessed patients undergoing ACLR. Four studies assessed protein-based supplementation. One study assessed creatine as a supplement. Four studies assessed vitamin-based supplementation. One study assessed testosterone supplementation. Protein and amino acid supplementation showed potential benefits; multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, graft maturation, muscular hypertrophic response, and peak dynamic muscle strength. When we examined creatine, vitamin, or hormone-based protocols, none demonstrated results, suggesting these factors may attenuate muscle atrophy after surgery. Vitamin C and E demonstrated potentially increased local inflammation in skeletal muscle, which runs contrary to the belief that antioxidant vitamin-based supplementation may decrease the inflammatory response that plays a role in the post injury/operative period. CONCLUSIONS: Protein-based supplementation may play a role in mitigating muscle atrophy associated with ACLR, as multiple authors demonstrated a combination of improved achievement of rehabilitation benchmarks, thigh hypertrophic response, and peak dynamic muscle strength. However, based on current literature, it is not possible to recommend a specific protein-based supplementation protocol at this time for patients undergoing ACLR. Limited evidence suggests no benefit for creatine, vitamin, or hormone-based protocols. LEVEL OF EVIDENCE: II, a systematic review of level I-II studies.

The Role of Resistance Training Dosing on Pain and Physical Function in Individuals With Knee Osteoarthritis: A Systematic Review.

CONTEXT: Dosing parameters are needed to ensure the best practice guidelines for knee osteoarthritis. OBJECTIVE: To determine whether resistance training affects pain and physical function in individuals with knee osteoarthritis, and whether a dose-response relationship exists. Second, we will investigate whether the effects are influenced by Kellgren-Lawrence grade or location of osteoarthritis. DATA SOURCES: A search for randomized controlled trials was conducted in MEDLINE, Embase, and CINAHL, from their inception dates, between November 1, 2018, and January 15, 2019. Keywords included knee osteoarthritis, knee joint, resistance training, strength training, and weight lifting. STUDY SELECTION: Inclusion criteria were randomized controlled trials reporting changes in pain and physical function on humans with knee osteoarthritis comparing resistance training interventions with no intervention. Two reviewers screened 471 abstracts; 12 of the 13 studies assessed were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2. DATA EXTRACTION: Mean baseline and follow-up Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and standard deviations were extracted to calculate the standard mean difference. Articles were assessed for methodological quality using the CONSORT (Consolidated Standards of Reporting Trials) 2010 scale and Cochrane Collaboration tool for assessing risk of bias. RESULTS: The 12 included studies had high methodological quality. Of these, 11 studies revealed that resistance training improved pain and/or physical function. The most common regimen was a 30- to 60-minute session of 2 to 3 sets of 8 to 12 repetitions with an initial resistance of 50% to 60% of maximum resistance that progressed over 3 sessions per week for 24 weeks. Seven studies reported Kellgren-Lawrence grade, and 4 studies included osteoarthritis location. CONCLUSION: Resistance training improves pain and physical function in knee osteoarthritis. Large effect sizes were associated with 24 total sessions and 8- to 12-week duration. No optimal number of repetitions, maximum strength, or frequency of sets or repetitions was found. No trends were identified between outcomes and location or Kellgren-Lawrence grade of osteoarthritis.

Molecular biogeography and host relations of a parasitoid fly.

Successful geographic range expansion by parasites and parasitoids may also require host range expansion. Thus, the evolutionary advantages of host specialization may trade off against the ability to exploit new host species encountered in new geographic regions. Here, we use molecular techniques and confirmed host records to examine biogeography, population divergence, and host flexibility of the parasitoid fly, Ormia ochracea (Bigot). Gravid females of this fly find their cricket hosts acoustically by eavesdropping on male cricket calling songs; these songs vary greatly among the known host species of crickets. Using both nuclear and mitochondrial genetic markers, we (a) describe the geographical distribution and subdivision of genetic variation in O. ochracea from across the continental United States, the Mexican states of Sonora and Oaxaca, and populations introduced to Hawaii; (b) demonstrate that the distribution of genetic variation among fly populations is consistent with a single widespread species with regional host specialization, rather than locally differentiated cryptic species; (c) identify the more-probable source populations for the flies introduced to the Hawaiian islands; (d) examine genetic variation and substructure within Hawaii; (e) show that among-population geographic, genetic, and host song distances are all correlated; and (f) discuss specialization and lability in host-finding behavior in light of the diversity of cricket songs serving as host cues in different geographically separate populations.

Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness.

BACKGROUND: Metabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalarial drug chloroquine activates the kinase ataxia telangiectasia mutated (ATM), improves metabolic syndrome and reduces atherosclerosis in mice. To translate this observation to humans, we conducted two clinical trials of chloroquine in people with the metabolic syndrome. METHODS: Eligibility included adults with at least 3 criteria of metabolic syndrome but who did not have diabetes. Subjects were studied in the setting of a single academic health center. The specific hypothesis: chloroquine improves insulin sensitivity and decreases atherosclerosis. In Trial 1, the intervention was chloroquine dose escalations in 3-week intervals followed by hyperinsulinemic euglycemic clamps. Trial 2 was a parallel design randomized clinical trial, and the intervention was chloroquine, 80 mg/day, or placebo for 1 year. The primary outcomes were clamp determined-insulin sensitivity for Trial 1, and carotid intima-media thickness (CIMT) for Trial 2. For Trial 2, subjects were allocated based on a randomization sequence using a protocol in blocks of 8. Participants, care givers, and those assessing outcomes were blinded to group assignment. RESULTS: For Trial 1, 25 patients were studied. Chloroquine increased hepatic insulin sensitivity without affecting glucose disposal, and improved serum lipids. For Trial 2, 116 patients were randomized, 59 to chloroquine (56 analyzed) and 57 to placebo (51 analyzed). Chloroquine had no effect on CIMT or carotid contrast enhancement by MRI, a pre-specified secondary outcome. The pre-specified secondary outcomes of blood pressure, lipids, and activation of JNK (a stress kinase implicated in diabetes and atherosclerosis) were decreased by chloroquine. Adverse events were similar between groups. CONCLUSIONS: These findings suggest that low dose chloroquine, which improves the metabolic syndrome through ATM-dependent mechanisms in mice, modestly improves components of the metabolic syndrome in humans but is unlikely to be clinically useful in this setting.Trial registration ClinicalTrials.gov (NCT00455325, NCT00455403), both posted 03 April 2007.