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Sarcopenia or muscle mass atrophy reportedly occurs in up to 50% of those aged >80 years and is a significant risk factor for functional disability and poor physical performance. Over time, the deterioration in both skeletal muscle quality and composition may compromise functional independence and has been shown to independently increase the risk for falls, fractures, and overall poor health in the elderly population. These are seen most obviously in older women. Given these serious consequences, much effort has been directed toward promoting increased activity and resistance training for muscle maintenance or even muscle regeneration in older adults. The Centers for Disease Control and Prevention states that for all adults ≥65 years of age, weekly aerobic and strength training are vital to healthy aging. Older patients who have not previously participated in strength training may be hesitant about starting a resistance training program and resort to simple and familiar aerobic exercise options such as walking, jogging, or cycling. However, the benefits of strength training are too important to miss: it can improve skeletal muscle metabolic capacity, mitigate effects of aging on functional capacity, maintain bone density, and, most importantly, help individuals maintain a higher quality of life and independence. Due to their increased risk of disability and injury, this opportunity for “exercise as medicine” is particularly important to women and must be encouraged by clinicians. As such, the purpose of this commentary was to highlight known sex-related differences in muscle metabolism and potential benefits of resistance training for elderly patients. A comprehensive understanding of the issues and prevention measures presented here may allow clinicians to better serve their patients, especially older female patients, and, ultimately, alleviate the burden placed on our society by our rapidly aging population.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, are non-functional, which may be due to the presence of the fungal sterol ergosterol instead of cholesterol. Here we engineer yeast to produce cholesterol and introduce diverse mu, delta, and kappa opioid receptors to create sensitive opioid biosensors that recapitulate agonist binding profiles and antagonist inhibition. Additionally, human mu opioid receptor variants, including those with clinical relevance, largely display expected phenotypes. By testing mu opioid receptor-based biosensors with systematically adjusted cholesterol biosynthetic intermediates, we relate sterol profiles to biosensor sensitivity. Finally, we apply sterol-modified backgrounds to other human receptors revealing sterol influence in SSTR5, 5-HTR4, FPR1, and NPY1R signaling. This work provides a platform for generating human G protein-coupled receptor-based biosensors, facilitating receptor deorphanization and high-throughput screening of receptors and effectors. The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. Here the authors engineer baker’s yeast to produce human sterols and show that vertebrate G protein coupled receptors are more sensitive in this membrane environment.

Background The construction and application of synthetic genetic circuits is frequently improved if gene expression can be orthogonally controlled, relative to the host. In plants, orthogonality can be achieved via the use of CRISPR-based transcription factors that are programmed to act on natural or synthetic promoters. The construction of complex gene circuits can require multiple, orthogonal regulatory interactions, and this in turn requires that the full programmability of CRISPR elements be adapted to non-natural and non-standard promoters that have few constraints on their design. Therefore, we have developed synthetic promoter elements in which regions upstream of the minimal 35S CaMV promoter are designed from scratch to interact via programmed gRNAs with dCas9 fusions that allow activation of gene expression. Results A panel of three, mutually orthogonal promoters that can be acted on by artificial gRNAs bound by CRISPR regulators were designed. Guide RNA expression targeting these promoters was in turn controlled by either Pol III (U6) or ethylene-inducible Pol II promoters, implementing for the first time a fully artificial Orthogonal Control System (OCS). Following demonstration of the complete orthogonality of the designs, the OCS was tied to cellular metabolism by putting gRNA expression under the control of an endogenous plant signaling molecule, ethylene. The ability to form complex circuitry was demonstrated via the ethylene-driven, ratiometric expression of fluorescent proteins in single plants. Conclusions The design of synthetic promoters is highly generalizable to large tracts of sequence space, allowing Orthogonal Control Systems of increasing complexity to potentially be generated at will. The ability to tie in several different basal features of plant molecular biology (Pol II and Pol III promoters, ethylene regulation) to the OCS demonstrates multiple opportunities for engineering at the system level. Moreover, given the fungibility of the core 35S CaMV promoter elements, the derived synthetic promoters can potentially be utilized across a variety of plant species.

The advent of Web-based sports injury surveillance via programs such as the High School Reporting Information Online system and the National Collegiate Athletic Association Injury Surveillance Program has aided the acquisition of data for girls' and women's field hockey injuries. To describe the epidemiology of injuries sustained in high school girls' field hockey in the 2008-2009 through 2013-2014 academic years and collegiate women's field hockey in the 2004-2005 through 2013-2014 academic years using Web-based sports injury surveillance. Descriptive epidemiology study. Online injury surveillance from field hockey teams in high school girls (annual average = 61) and collegiate women (annual average = 14). Girls' and women's field hockey players who participated in practices and competitions during the 2008-2009 through 2013-2014 high school academic years and the 2004-2005 through 2013-2014 collegiate academic years. Athletic trainers collected time-loss (≥24 hours) injury and exposure data. Injury rates per 1000 athlete-exposures (AEs), injury rate ratios (IRRs) with 95% confidence intervals (CIs), and injury proportions by body site and diagnosis were calculated. The High School Reporting Information Online system documented 983 time-loss injuries during 569 551 AEs; the National Collegiate Athletic Association Injury Surveillance Program documented 996 time-loss injuries during 185 984 AEs. The injury rate from 2008-2009 through 2013-2014 was higher in college than in high school (3.25 versus 1.73/1000 AEs; IRR = 1.89; 95% CI = 1.63, 2.18). Most injuries occurred during practices in high school (52.0%) and college (60.7%). Injury rates were higher during competitions than practices in high school (IRR = 2.00; 95% CI = 1.76, 2.26) and college (IRR = 1.96; 95% CI = 1.73, 2.23). At both levels, injuries most commonly occurred to the lower extremity and head/face and resulted in muscle/tendon strains and contusions. However, injury patterns varied between practices and competitions. Injury rates and patterns varied across age groups and between practices and competitions, highlighting the need for development of targeted injury-prevention strategies at both levels of play.

Case. We report an 11-year-old male who sustained a lesser tuberosity avulsion fracture of the proximal humerus upon making contact with a baseball during an at-bat. This injury was neglected for 14 months and was eventually detected by an axillary radiograph and subsequent MRI. He successfully underwent an open surgical repair and regained full range of motion and level of activity at 1-year follow-up. Conclusion. In pediatric baseball players, lesser tuberosity avulsion fractures may occur upon striking a baseball with a bat. Even after being neglected for several months, these injuries can be treated successfully with an open surgical repair.

Background: Evidence shows that after anterior cruciate ligament (ACL) reconstruction, patients may have varied access to physical therapy. In particular, physical therapy input may end many months before patients reach full recovery. Telerehabilitation may provide an opportunity to address this rehabilitation gap and improve access to evidence-based rehabilitation alongside physical therapy at all stages of care. Objective: This study aims to understand the opinions of patients who have undergone ACL surgery and rehabilitation on the use of telerehabilitation as part of ACL care and define the population and explore their experiences and views on the acceptability of telerehabilitation after ACL reconstruction. Methods: This study was a cross-sectional, voluntary, web-based survey combining both closed and open questions. Ethical approval was obtained from the Yale School of Medicine Institutional Review Board. Participants were aged 16 years or older at the time of recruitment and had undergone ACL reconstruction within the past 5 years. A 26-item survey was developed using the Qualtrics survey platform. No items were mandatory. Responses were multiple choice, binary, and qualitative. The CHERRIES (Checklist for Reporting Results of Internet E-Surveys) was used to ensure the quality of reporting of surveys in the medical literature. Data were analyzed using Stata version 15. Qualitative data were analyzed using NVivo 11. The theoretical framework for this analysis is based on the Capability, Opportunity, and Motivation-Behavior model of behavior change. Results: A total of 100 participants opened the survey. All completers were unique. The participation and completion rates were each 96% (96/100). Patients reported their physical therapy care ended at an average of 6.4 months and that they felt fully recovered at an average of 13.2 months. Only 26% (25/96) of patients felt fully recovered at the end of physical therapy. Of these 96 patients, 54 (60%) were younger than 30 years, 71 (74%) were recreational athletes, 24 (24%) were competitive athletes, 72 (75%) had private insurance, 74 (77%) were not familiar at all with telerehabilitation, and 89% (85/96) felt capable. They preferred to use telerehabilitation at different stages of care. Reported benefits included resource saving, improved access to care, improved learning, and greater engagement. Concerns included incorrect performance of exercises or unmanaged pain being missed and less access to manual therapy, motivation, and opportunities to ask questions. Participants’ priorities for a future telerehabilitation intervention included its use as an adjunct to physical therapy rather than a replacement, with content available for each stage of care, especially return to sports. Participants stressed that the intervention should be personalized to them and include measures of progress. Conclusions: These findings helped understand and define the ACL reconstruction population. Participants found telerehabilitation acceptable in principle and highlighted the key user requirements and scope of future interventions.

Yeast expression of human G-protein-coupled receptors (GPCRs) can be used as a biosensor platform for the detection of pharmaceuticals. Cannabinoid receptor type 1 (CB1R) is of particular interest, given the cornucopia of natural and synthetic cannabinoids being explored as therapeutics. We show for the first time that engineering the N-terminus of CB1R allows for efficient signal transduction in yeast, and that engineering the sterol composition of the yeast membrane modulates its performance. Using an engineered cannabinoid biosensor, we demonstrate that large libraries of synthetic cannabinoids and terpenes can be quickly screened to elucidate known and novel structure–activity relationships. The biosensor strains offer a ready platform for evaluating the activity of new synthetic cannabinoids, monitoring drugs of abuse, and developing therapeutic molecules.

ObjectiveConcussion symptoms can be clustered into domains and understanding how multiple symptom domains present clinically may guide more accurate interventions. We investigate the associations between concurrent symptom domains and clinical recovery outcomes, as well as the role of sex in these relationships.MethodsWe analysed data from the Ivy League–Big Ten Epidemiology of Concussion Study and included sport-related concussions (SRC) across five academic years 2015–2016/2019–2020 with complete data (n=1160). We used symptoms from the Sport Concussion Assessment Tool 22-symptom evaluation, previously categorised into symptom domains. Symptom profiles characterise how athletes endorse concurrent symptom domains. Outcomes are time (in days) from SRC to symptom resolution, return to academics, and full play.ResultsFemales more commonly endorsed headache, sensory, and affective symptom domains. Four classes/symptom profiles emerged: (1) ‘low’ on all domains, (2) ‘high’ on headache and sensory domains, (3) ‘high’ on vestibulo-ocular, cognitive, and sleep domains, and (4) ‘high’ on all domains. Time to symptom resolution, return to academics, and return to play were consistently shorter among class/symptom profile 1 compared with other classes/profiles. Compared with class/profile 1, the chance of having symptoms resolve was lower among classes/profiles 2, 3, and 4 (HR 0.74, 95% CI 0.63 to 0.88; HR 0.74, 95% CI 0.60 to 0.92; HR 0.50, 95% CI 0.43 to 0.57, respectively). Results were similar for return to academics and full play outcomes. Interactions with sex were not statistically significant.ConclusionsFour symptom profiles characterised how concussion symptom domains co-occur. We found differences in recovery timelines among these groups, but not by sex. Findings inform and support targeted, symptom domain-specific interventions in concussion management.

Purpose Alpine skiing and snowboarding are both popular winter sports that can be associated with significant orthopaedic injuries. However, there is a lack of nationally representative injury data for the two sports. Methods The National Trauma Data Bank was queried for patients presenting to emergency departments due to injuries sustained from skiing and snowboarding during 2011 and 2012. Patient demographics, comorbidities, and injury patterns were tabulated and compared between skiing and snowboarding. Risk factors for increased injury severity score and lack of helmet use were identified using multivariate logistic regression. Results Of the 6055 patients identified, 55.2 % were skiers. Sixty-one percent had fractures. Lower extremity fractures were the most common injury and occurred more often in skiers ( p  < 0.001). Upper extremity fractures were more common in snowboarders, particularly distal radius fractures ( p  < 0.001). On multivariate analysis, increased injury severity was independently associated with age 18–29, 60–69, 70+, male sex, a positive blood test for alcohol, a positive blood test for an illegal substance, and wearing a helmet. Lack of helmet use was associated with age 18–29, 30–39, smoking, a positive drug test for an illegal substance, and snowboarding. Conclusions Young adults, the elderly, and those using substances were shown to be at greater risk of increased injury severity and lack of helmet use. The results of this study can be used clinically to guide the initial assessment of these individuals following injury, as well as for targeting preventive measures and education. Level of evidence Prognostic Level III.

Background: Physical therapy (PT) rehabilitation is critical to successful outcomes after anterior cruciate ligament reconstruction (ACLR). Later-stage rehabilitation, including sport-specific exercises, is increasingly recognized for restoring high-level knee function. However, supervised PT visits have historically been concentrated during the early stages of recovery after ACLR. Purpose/Hypothesis: To assess the number and temporal utilization of PT visits after ACLR in a national cohort. We hypothesized that PT visits would be concentrated early in the postoperative period. Study Design: Descriptive epidemiological study. Methods: The Humana PearlDiver database was searched to identify patients who underwent ACLR between 2007 and 2017. Patients with additional structures treated were excluded. The mean ± SD, median and interquartile range (IQR), and range of number of PT visits for each patient were determined for the 52 weeks after ACLR. PT visits over time were also assessed in relation to patient age and sex. Results: In total, 11,518 patients who underwent ACLR met the inclusion criteria; the mean age was 32.62 ± 13.70 years, and 42.7% were female patients. Of this study cohort, 10,381 (90.4%) had documented PT postoperatively; the range of PT visits was 0 to 121. On average, patients had 16.90 ± 10.60 PT visits (median [IQR], 16 [9-22]) after ACLR. Patients completed a mean of 52% of their PT visits in the first 6 weeks, 75% in the first 10 weeks, and 90% in the first 16 weeks after surgery. Patients aged 10 to 19 years had the highest number of PT visits (mean ± SD, 19.67 ± 12.09; median [IQR], 18 [12-25]), significantly greater than other age groups (P < .001). Conclusion: PT after ACLR is concentrated in the early postoperative period. Physicians, therapists, and patients may consider adjusting the limited access to PT to optimize patient recovery. Clinical Relevance: As supervised PT visits may be limited, the appropriate temporal utilization of supervised PT visits must be maximized. Strategies to ensure sessions for later neuromuscular and activity-specific rehabilitation are needed.