Development, validation and reliability of a questionnaire to evaluate coaches' and players' perceptions, learning, and resources regarding the ruck in rugby union.

Background: The lack of a reliable research tool for assessing the attitudes, behaviours, and learning resources of rugby coaches and players regarding the ruck event is a significant gap in rugby research. Objectives: This study aimed to adapt an existing questionnaire focused on the tackle event and to validate and establish the reliability of the instrument. The questionnaire explores the attitudes, behaviours, and learning resources of rugby coaches and players, with a focus on the ruck event and its impact on coach and player development, as well as coaching practices. Methods: A seven-step design process was followed to validate the questionnaire's content, construct, clarity, and relevance. A panel of 12 experts evaluated the questionnaire, followed by a test-retest procedure involving 15 coaches and 16 players, highlighting the effectiveness of this questionnaire, and emphasising its potential to generate data that can impact the field of rugby coaching and player development. Results: The questionnaire was deemed appropriate and clear by the expert panel, with an average completion time of 22 minutes. Moderate to good agreement was observed among players (ICC Agreement = 0.71) and coaches (ICC Agreement = 0.88), with high response consistency (ICC Consistency = 0.71 for players and 0.87 for coaches). Significant agreement was also found in Kendall's W scores (players = 0.85, coaches = 0.93, p<0.01). Conclusion: This study presents a developed questionnaire noted for its clarity, reliability, and consistency. It serves as a valuable tool for future rugby research, with the potential to impact coach and player development significantly.

Sport Specialization and Sport Motivation in Middle School-Aged Athletes.

CONTEXT: Sport specialization has been assumed to have psychosocial ramifications for athletes, especially autonomous motivation, which has been associated with continued sport participation. Sport dropout is common in youth athletes, yet it is unknown how sport specialization may affect this population psychosocially. OBJECTIVE: To determine the association of sport specialization with autonomous and controlled motivation and amotivation in middle school-aged athletes. DESIGN: Cross-sectional study. SETTING: An anonymous online questionnaire was distributed to athletes via schools, club sports, and social media. PATIENTS OR OTHER PARTICIPANTS: A total of 178 athletes (male = 59%; private school = 51%; grade: sixth = 20%, seventh = 32%, eighth = 48%) completed the questionnaire. MAIN OUTCOME MEASURE(S): The questionnaire assessed demographics, sport participation, and motivation using the Youth Behavioral Regulation in Sport Questionnaire. Sport specialization was defined using a modified 3-point scale (low, moderate, or high) and multisport versus single-sport athletes. Nonparametric tests were used to analyze the differences among the types of motivation and specialization levels and between multisport and single-sport athletes. RESULTS: Sport specialization categories were not significantly associated with autonomous motivation, controlled motivation, or amotivation. No significant associations were present between multisport or single-sport athletes and any type of motivation. However, multisport athletes had higher scores for intrinsic motivation, a subscale of autonomous motivation, compared with single-sport athletes (single sport: median = 5.00, 25th-75th quartile = 4.50-5.00; multisport: median = 5.00, 25th-75th quartile = 5.00-5.00; P = .04). CONCLUSIONS: Sport motivation did not differ between sport specialization groups in middle school athletes. Dropout from sport is common in this age group but is multifactorial in nature. A lack of sport motivation could be a factor for some athletes, but all specialization groups appeared to have similar outcomes. Our exploratory analysis suggests that clinicians may consider having an open dialogue with single-sport athletes, their parents or guardians, and coaches to ensure that athletes are enjoying their sport.

An assessment of a biosensor system for the quantification of microcystins in freshwater cyanobacterial blooms.

Microcystin-producing cyanobacterial blooms are a global issue threatening drinking water supplies and recreation on lakes and beaches. Direct measurement of microcystins is the only way to ensure waters have concentrations below guideline concentrations; however, analyzing water for microcystins takes several hours to days to obtain data. We tested LightDeck Diagnostics' bead beater cell lysis and two versions of the quantification system designed to give microcystin concentrations within 20 min and compared it to the standard freeze-thaw cycle lysis method and ELISA quantification. The bead beater lyser was only 30 % effective at extracting microcystins compared to freeze-thaw. When considering freeze-thaw samples analyzed in 2021, there was good agreement between ELISA and LightDeck version 2 (n = 152; R2 = 0.868), but the LightDeck slightly underestimated microcystins (slope of 0.862). However, we found poor relationships between LightDeck version 2 and ELISA in 2022 (n = 49, slopes 0.60 to 1.6; R2 < 0.6) and LightDeck version 1 (slope = 1.77 but also a high number of less than quantifiable concentrations). After the quantification issues are resolved, combining the LightDeck system with an already-proven rapid lysis method (such as microwaving) will allow beach managers and water treatment operators to make quicker, well-informed decisions.

Measurement of Direct-Photon Cross Section and Double-Helicity Asymmetry at sqrt[s]=510 GeV in p[over →]+p[over →] Collisions.

We present measurements of the cross section and double-helicity asymmetry A_{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510 GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510 GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

OBJECTIVES: The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. METHODS: The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. RESULTS: Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. CONCLUSIONS: Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review.

Nrf2 is a major transcription factor that significantly regulates-directly or indirectly-more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that are seemingly unrelated to oxidative stress. In the past 25 years, the number of factors involved in the activation, nuclear translocation, and deactivation of Nrf2 has continued to expand. The purpose of this review is to provide an overview of the remarkable complexity of the tortuous sequence of stop-and-go signals that not only regulate expression or repression, but may also modify transcriptional intensity as well as the specificity of promoter recognition, allowing fluidity of its gene expression profile depending on the various structural modifications the transcription factor encounters on its journey to the DNA. At present, more than 45 control points have been identified, many of which represent sites of action of the so-called Nrf2 activators. The complexity of the pathway and the synergistic interplay among combinations of control points help to explain the potential advantages seen with phytochemical compositions that simultaneously target multiple control points, compared to the traditional pharmaceutical paradigm of "one-drug, one-target".

Recommendations for Medical Discharge Documentation and Academic Supports for University Students Recovering From Concussion.

OBJECTIVE: This study sought to (1) collate the experiences of university students with concussion history and academic stakeholders through interviews and (2) develop concussion management recommendations for institutions of higher learning using a multidisciplinary Delphi procedure. SETTING: Remote semistructured interviews and online surveys. PARTICIPANTS: The first aim of this study included undergraduate university students with concussion history who did not participate in varsity athletics ( n = 21; 57.1% female), as well as academic faculty/staff with experience assisting university students with their postconcussion academic needs ( n = 7; 71.4% female). The second aim enrolled 22 participants (54.5% female) to serve on the Delphi panel including 9 clinicians, 8 researchers, and 5 academic faculty/staff. DESIGN: An exploratory-sequential mixed-methods approach. MAIN MEASURES: Semistructured interviews were conducted to unveil barriers regarding the return-to-learn (RTL) process after concussion, with emergent themes serving as a general framework for the Delphi procedure. Panelists participated in 3 stages of a modified Delphi process beginning with a series of open-ended questions regarding postconcussion management in higher education. The second stage included anonymous ratings of the recommendations, followed by an opportunity to review and/or modify responses based on the group's consensus. RESULTS: The results from the semistructured interviews indicated students felt supported by their instructors; however, academic faculty/staff lacked information on appropriate academic supports and/or pathways to facilitate the RTL process. Of the original 67 statements, 39 achieved consensus (58.2%) upon cessation of the Delphi procedure across 3 main categories: recommendations for discharge documentation (21 statements), guidelines to facilitate a multidisciplinary RTL approach (10 statements), and processes to obtain academic supports for students who require them after concussion (8 statements). CONCLUSIONS: These findings serve as a basis for future policy in higher education to standardize RTL processes for students who may need academic supports following concussion.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger: A causal inference mediation analysis.

Background: Gender inequity, a deeply-rooted driver of poor health globally, is expressed in society through gender norms, the unspoken rules that govern gender-related roles and behavior. The development of public health interventions focused on promoting equitable gender norms are gaining momentum internationally, but there remain critical gaps in the evidence about how these interventions are working to change behavioral outcomes. Methods: A four-arm cluster randomized control trial (cRCT) was conducted to evaluate the effects of the Reaching Married Adolescents in Niger (RMA) intervention on modern contraceptive use and intimate partner violence (IPV) among married adolescent girls and their husbands in Dosso, Niger (T1: 1042 dyads; 24 mos. follow-up: 737 dyads, 2016-2019). This study seeks to understand if changes in perceived inequitable gender norms among husbands are the mechanism behind effects on modern contraceptive use and IPV. We estimated natural direct and indirect effects via these gender norms using inverse odds ratio weighting. An intention-to-treat approach and a difference-in-differences estimator in a hierarchical linear probability model was used to estimate prevalence differences, along with bootstrapping to estimate confidence intervals. Results: The total effects of the RMA small group intervention (Arm 2) is estimated to be an 8% reduction in prevalence of IPV [95% CI: -0.18, 0.01]. For this arm, the natural indirect effect through gender inequitable social norms is associated with a 2% decrease (95% CI: -0.07, 0.12), accounting for 22.3% of this total effect, and the natural direct effect with a 6% decrease (95% CI: -0.20, -0.02) in IPV. Of the total effect of the RMA household visit intervention (Arm 1) on contraceptive use (20% increase), indirect effects via inequitable gender norms were associated with an 11% decrease (95% CI: -0.18, -0.01) and direct effects with a 32% increase (95% CI: 0.13, 0.44) in contraceptive use. For the combination arm, of the total effects on contraceptive use (19% increase), indirect effects were associated with a 9% decrease (95% CI: -0.20, 0.02) and direct effects with a 28% increase (95% CI: 0.12, 0.46). Conclusion: The present study contributes experimental evidence that the small group RMA intervention reduced IPV partially via reductions in perceived inequitable gender norms among husbands. Evidence also suggests that increases in perceived inequitable gender norms resulted in decreased contraceptive use among those receiving the household visit intervention component. Not only do these results open the "black box" around how the RMA small group intervention may create behavior change to help inform its future use, they provide evidence supporting behavior change theories and frameworks that postulate the importance of changing underlying social norms in order to reduce IPV and increase modern contraceptive use.

The role of adjuvant treatment for early-stage uterine clear cell carcinomas.

BACKGROUND: Uterine clear cell carcinoma is a rare and aggressive subtype of endometrial carcinoma. Prospective clinical trials have not been feasible for this rare tumor, and data regarding the optimal adjuvant treatment regimen for early-stage uterine clear cell carcinomas is limited. Our study's objective was to determine if adjuvant chemotherapy or radiation therapy improves patients' outcomes in stage I and II uterine clear cell carcinoma. METHODS: Patients with stage I and II uterine clear cell carcinoma were identified at a single institution. All cases were reviewed by a gynecologic pathologist. Both pure and mixed non-serous uterine clear cell carcinomas were included. Primary outcomes were recurrence free survival and overall survival. RESULTS: A total of 71 patients were identified including 39 (55%) pure and 32 (45%) mixed clear cell carcinoma. Most patients were FIGO stage IA (77.5%). Most patients (n = 58, 82%) received adjuvant therapy, including 43 (61%) receiving chemotherapy, 50 (70%) receiving radiation therapy, and 35 (49%) receiving both. Recurrence free survival was not significantly different among patients receiving no or <6 cycles of chemotherapy versus patients receiving 6 cycles of chemotherapy (p = 0.39). However, median OS was significantly different among patients receiving no or <6 cycles of chemotherapy versus 6 cycles of chemotherapy (p = 0.004). On univariable analysis, 6 cycles of chemotherapy was significantly associated with improved OS (HR 0.1, 95% CI 0.01-0.07). Presence of LVSI, mutated p53, number of pelvic and para-aortic lymph nodes assessed, adjuvant chemotherapy (any number of cycles), and >2 medical co-morbidities were not significant predictors of OS on univariable analysis. On multivariable analysis, 6 cycles of adjuvant chemotherapy remained a significant predictor of improved OS (HR 0.1, 95% CI 0.01-0.8). CONCLUSIONS: In this study, administration of 6 cycles of chemotherapy appears to significantly improve OS. This finding suggests consideration of 6 cycles of adjuvant chemotherapy in patients with early-stage uterine clear cell carcinoma, however clinical trials are needed to confirm these findings.

Secondary School Athletic Trainers' Strategies and Barriers to Overuse Injury Treatment in Adolescent Athletes.

CONTEXT: Studies have illustrated that overuse injuries occur in adolescent athletes more often than previously reported. The general purpose of this study was to provide a thorough report of secondary school athletic trainers encounters, practices, and perceptions of overuse injury in adolescent athletes. DESIGN: Cross-sectional. METHODS: An anonymous online questionnaire was distributed via email to athletic trainers in the secondary school setting. The questionnaire was sent to participants during the summer of 2021 and 430 participants (highest educational degree earned: master's degree = 66%) completed the survey. Various survey methods were used to evaluate athletic trainers (1) demographics, (2) estimations about what percentage of injuries evaluated and treated were classified as overuse, (3) methods for treating overuse injuries, (4) confidence in treating overuse injuries and the complete implementation of their treatment plan, (5) perceptions of various barriers to treating overuse injuries, and (6) perception as to why patients did not want to reduce activity to treat their overuse injuries. RESULTS: Participants reported that about half of all evaluations and treatments in a year were overuse injuries and they were "fairly" or "completely" confident (90%) in their ability to treat these injuries. The most common treatments cited were stretching (91%) and reducing activity (90%). Only 61% of participants were "fairly" or "completely" confident in the complete implementation of their treatment plan. Participants believed that patients' reluctance to reduce sport activities (82% "moderate" or "extreme" barrier) was the most significant barrier to treatment. Participants cited athletes' avoidance of missing games as the most common reason athletes were reluctant to reduce sporting activity. CONCLUSIONS: Participants felt confident in treating overuse injuries yet faced significant barriers in treating these injuries. Clinicians should be prepared to have conversations about the importance of reducing sporting activity to allow proper healing for overuse injuries in adolescent athletes.

Optimizing Concussion Care Seeking: A Longitudinal Analysis of Recovery.

BACKGROUND: Approximately half of concussions go undisclosed and therefore undiagnosed. Among diagnosed concussions, 51% to 64% receive delayed medical care. Understanding the influence of undiagnosed concussions and delayed medical care would inform medical and education practices. PURPOSE: To compare postconcussion longitudinal clinical outcomes among (1) individuals with no concussion history, all previous concussions diagnosed, and ≥1 previous concussion undiagnosed, as well as (2) those who have delayed versus immediate symptom onset, symptom reporting, and removal from activity after concussion. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Participants included 2758 military academy cadets and intercollegiate athletes diagnosed with concussion in the CARE Consortium. We determined (1) each participant's previous concussion diagnosis status self-reported at baseline (no history, all diagnosed, ≥1 undiagnosed) and (2) whether the participant had delayed or immediate symptom onset, symptom reporting, and removal from activity. We compared symptom severities, cognition, balance, and recovery duration at baseline, 24 to 48 hours, date of asymptomatic status, and date of unrestricted return to activity using tests of parallel profiles. RESULTS: The ≥1 undiagnosed concussion group had higher baseline symptom burdens (P < .001) than the other 2 groups and poorer baseline verbal memory performance (P = .001) than the all diagnosed group; however, they became asymptomatic and returned to activity sooner than those with no history. Cadets/athletes who delayed symptom reporting had higher symptom burdens 24 to 48 hours after injury (mean ± SE; delayed, 28.8 ± 0.8; immediate, 20.6 ± 0.7), took a median difference of 2 days longer to become asymptomatic, and took 3 days longer to return to activity than those who had immediate symptom reporting. For every 30 minutes of continued participation after injury, days to asymptomatic status increased 8.1% (95% CI, 0.3%-16.4%). CONCLUSION: Clinicians should expect that cadets/athletes who delay reporting concussion symptoms will have acutely higher symptom burdens and take 2 days longer to become asymptomatic. Educational messaging should emphasize the clinical benefits of seeking immediate care for concussion-like symptoms.

Impact of COVID-19 on the physical activity, quality of life and mental health of adolescent athletes: a 2-year evaluation of over 17 000 athletes.

PURPOSE: To evaluate the changes in mental health, quality of life (QOL) and physical activity (PA) among adolescent athletes during the COVID-19 pandemic as organised sports resumed. METHODS: Adolescent athletes completed surveys including demographic and sport participation information, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pediatric Quality of Life Inventory and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale in May 2020 following COVID-19-related sport cancellations (Spring20) and after returning to sports in May 2021 (Spring21). The groups were balanced by inverse propensity score weighting and compared using analysis of variance models and ordinal regression models. RESULTS: 17 421 participants were included (Spring20=13 002; Spring21=4419; 16.2±1.2 years; 53% female). Anxiety was significantly lower (better) in Spring21 (Spring20=7.0, 95% CI 6.9 to 7.1; Spring21=4.9, 95% CI 4.8 to 5.0, p<0.001), as was the prevalence of moderate to severe anxiety (Spring20=29.4%, Spring21=17.1%, p<0.001). Depression was significantly improved in Spring21 (Spring20=7.6, 95% CI 7.5 to 7.7; Spring21=4.6, 95% CI 4.5 to 4.8, p<0.001), as was the prevalence of moderate to severe depression (Spring20=32.2%, Spring21=15.4%, p<0.001). Athletes in Spring21 reported higher QOL (Spring20=79.6, 95% CI 79.3 to 79.9; Spring21=84.7, 95% CI 84.4 to 85.0, p<0.001) and increased levels of PA (Spring20=13.8, 95% CI 13.6 to 13.9; Spring21=22.7, 95% CI 22.6 to 22.9, p<0.001). CONCLUSION: Early COVID-19 sports restrictions were associated with worsening mental health in adolescents. In 2021, after returning to sports, athletes reported significant improvements in mental health, QOL and PA, although mental health adversities remain an important priority.

Achieving Consensus Through a Modified Delphi Technique to Create the Post-concussion Collegiate Return-to-Learn Protocol.

BACKGROUND: Sport-related concussions (SRCs) affect millions of adolescents and young adults annually in the USA; however, current SRC consensus statements provide limited guidance on academic support for students within higher education. OBJECTIVE: To generate consensus on appropriate academic recommendations for clinicians, students, and academic stakeholders to support university students during their recovery. METHODS: Panelists participated in three stages of a modified Delphi procedure: the first stage included a series of open-ended questions after reviewing a literature review on post-SRC return-to-learn (RTL) in higher education; the second stage asked panelists to anonymously rate the recommendations developed through the first Delphi stage using a 9-point scale; and the final stage offered panelists the opportunity to change their responses and/or provide feedback based on the group's overall ratings. RESULTS: Twenty-two panelists including clinicians, concussion researchers, and academic stakeholders (54.5% female) from 15 institutions and/or healthcare systems participated in a modified Delphi procedure. A total of 42 statements were developed after round one. Following the next two rounds, 27 statements achieved consensus amongst the panel resulting in the four-stage Post-Concussion Collegiate RTL Protocol. CONCLUSION: There are several unique challenges when assisting university students back to the classroom after SRC. Explicit guidelines on when to seek additional medical care (e.g., if they are experiencing worsening or persistent symptoms) and how to approach their instructor(s) regarding academic support may help the student self-advocate. Findings from the present study address barriers and provide a framework for universities to facilitate a multidisciplinary approach amongst medical and academic stakeholders.

Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.

Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis. We hypothesized daily treatment with a purported Nrf2 activator, PB125, in Hartley guinea pigs, a model of musculoskeletal decline, would attenuate the progression of skeletal muscle mitochondrial dysfunction and impaired proteostasis and preserve musculoskeletal function. We treated 2- and 5-month-old male and female Hartley guinea pigs for 3 and 10 months, respectively, with the phytochemical compound PB125. Longitudinal assessments of voluntary mobility were measured using Any-MazeTM open-field enclosure monitoring. Cumulative skeletal muscle protein synthesis rates were measured using deuterium oxide over the final 30 days of treatment. Mitochondrial oxygen consumption in soleus muscles was measured using high resolution respirometry. In both sexes, PB125 (1) increased electron transfer system capacity; (2) attenuated the disease/age-related decline in coupled and uncoupled mitochondrial respiration; and (3) attenuated declines in protein synthesis in the myofibrillar, mitochondrial and cytosolic subfractions of the soleus. These effects were not associated with statistically significant prolonged maintenance of voluntary mobility in guinea pigs. Collectively, treatment with PB125 contributed to maintenance of skeletal muscle mitochondrial respiration and proteostasis in a pre-clinical model of musculoskeletal decline. Further investigation is necessary to determine if these documented effects of PB125 are also accompanied by slowed progression of other aspects of musculoskeletal dysfunction. KEY POINTS: Aside from exercise, there are no effective interventions for musculoskeletal decline, which begins in the fifth decade of life and contributes to disability and cardiometabolic diseases. Targeting both mitochondrial dysfunction and impaired protein homeostasis (proteostasis), which contribute to the age and disease process, may mitigate the progressive decline in overall musculoskeletal function (e.g. gait, strength). A potential intervention to target disease drivers is to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2) activation, which leads to the transcription of genes responsible for redox homeostasis, proteome maintenance and mitochondrial energetics. Here, we tested a purported phytochemical Nrf2 activator, PB125, to improve mitochondrial function and proteostasis in male and female Hartley guinea pigs, which are a model for musculoskeletal ageing. PB125 improved mitochondrial respiration and attenuated disease- and age-related declines in skeletal muscle protein synthesis, a component of proteostasis, in both male and female Hartley guinea pigs.

Optimizing Concussion Care Seeking: The Influence of Previous Concussion Diagnosis Status on Baseline Assessment Outcomes.

BACKGROUND: The prevalence of unreported concussions is high, and undiagnosed concussions can lead to worse postconcussion outcomes. It is not clear how those with a history of undiagnosed concussion perform on subsequent standard concussion baseline assessments. PURPOSE: To determine if previous concussion diagnosis status was associated with outcomes on the standard baseline concussion assessment battery. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Concussion Assessment, Research, and Education (CARE) Consortium participants (N = 29,934) self-reported concussion history with diagnosis status and completed standard baseline concussion assessments, including assessments for symptoms, mental status, balance, and neurocognition. Multiple linear regression models were used to estimate mean differences and 95% CIs among concussion history groups (no concussion history [n = 23,037; 77.0%], all previous concussions diagnosed [n = 5315; 17.8%], ≥1 previous concussions undiagnosed [n = 1582; 5.3%]) at baseline for all outcomes except symptom severity and Brief Symptom Inventory-18 (BSI-18) score, in which negative binomial models were used to calculate incidence rate ratios (IRRs). All models were adjusted for sex, race, ethnicity, sport contact level, and concussion count. Mean differences with 95% CIs excluding 0.00 and at least a small effect size (≥0.20), and those IRRs with 95% CIs excluding 1.00 and at least a small association (IRR, ≥1.10) were considered significant. RESULTS: The ≥1 previous concussions undiagnosed group reported significantly greater symptom severity scores (IRR, ≥1.38) and BSI-18 (IRR, ≥1.31) scores relative to the no concussion history and all previous concussions diagnosed groups. The ≥1 previous concussions undiagnosed group performed significantly worse on 6 neurocognitive assessments while performing better on only 2 compared with the no concussion history and all previous concussions diagnosed groups. There were no between-group differences on mental status or balance assessments. CONCLUSION: An undiagnosed concussion history was associated with worse clinical indicators at future baseline assessments. Individuals reporting ≥1 previous undiagnosed concussions exhibited worse baseline clinical indicators. This may suggest that concussion-related harm may be exacerbated when injuries are not diagnosed.

Contemporary Analysis of Inconsistencies Between Physician-reported Disclosures at the AAOS Annual Meeting and Industry-reported Financial Disclosures in the Open Payments Database.

INTRODUCTION: Healthcare regulators and patients are increasingly interested in financial transparency between physicians and the industry because of concerns of bias. METHODS: Disclosures for every first and last author with a medical degree from the United States associated with a poster or podium presentation at the American Academy of Orthopaedic Surgeons (AAOS) 2019 Annual Meeting were identified. Author characteristics were collected. AAOS disclosures were then compared with disclosures from the Open Payments Database to determine whether any inconsistencies existed. RESULTS: In total, 2,503 AAOS presenters were identified, and 1,380 authors met the inclusion criteria. Using AAOS disclosures as the standard comparator, 482 authors (35%) had an inconsistency in any category between AAOS disclosures and the Open Payments Database. Inconsistency rates for each category were 8% for royalties, 10% for speaker's fee, 15% for paid consultant, 16% for research, 14% for stocks, and 1% for other financial support. DISCUSSION: Although the inconsistency rate for each category has improved over the years, the overall inconsistency rate between physician-reported disclosures at a recent AAOS Annual Meeting and industry-reported relationships reported in the Open Payments Database was still 35%.

Mobile Subthreshold Exercise Program (MSTEP) for concussion: study protocol for a randomized controlled trial.

BACKGROUND: Subthreshold exercise, defined as aerobic exercise below the level that causes symptoms, has been utilized as a treatment for youth with persistent postconcussive symptoms (PPCS), but there is currently little evidence to guide use. In addition, prior studies of exercise for PPCS have all required multiple in-person visits. We developed a virtual approach for delivering subthreshold exercise to youth with PPCS called the Mobile Subthreshold Exercise Program (MSTEP), and we have now been funded to conduct a large national randomized controlled trial (RCT) to test its efficacy for reducing concussive symptoms and improving health-related quality of life. METHODS: This investigation is an RCT comparing MSTEP to an active control. We will recruit 200 adolescents 11-18 years old with postconcussive symptoms persisting for at least 1 week but less than 1 year. Youth will be randomized to receive either 6 weeks of subthreshold exercise (MSTEP) or a stretching condition (control). Youth and parents will complete surveys of concussive symptoms at baseline, weekly during the intervention, and at 3 and 6 months. The primary outcomes will be trajectory of concussive symptoms and health-related quality of life over the 6 months of the study. Secondary outcomes will include depression, anxiety, and sleep quality. We will also assess potential mediators of treatment effects including moderate-vigorous physical activity and fear avoidance of concussive symptoms. DISCUSSION: This multisite RCT of MSTEP will provide vital information regarding the efficacy of a virtually delivered subthreshold exercise program for youth with PPCS, and insight regarding potential mediators of treatment effects, including objectively measured physical activity and fear avoidance of concussive symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04688255. Registered on December 29, 2020.

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AIMS: Substantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes. MATERIALS AND METHODS: A retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan-Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI. RESULTS: In 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05). DISCUSSION: Substantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.