Rapid characterization of spike variants via mammalian cell surface display.

The SARS-CoV-2 spike protein is a critical component of vaccines and a target for neutralizing monoclonal antibodies (nAbs). Spike is also undergoing immunogenic selection with variants that increase infectivity and partially escape convalescent plasma. Here, we describe Spike Display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ∼200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by 13 nAbs. An alanine scan of all five N-terminal domain (NTD) loops highlights a public epitope in the N1, N3, and N5 loops recognized by most NTD-binding nAbs. NTD mutations in variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.1.28 (gamma), B.1.427/B.1.429 (epsilon), and B.1.617.2 (delta) impact spike expression and escape most NTD-targeting nAbs. Finally, B.1.351 and B.1.1.28 completely escape a potent ACE2 mimic. We anticipate that Spike Display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.

Engineering a human P2X2 receptor with altered ligand selectivity in yeast.

P2X receptors are a family of ligand gated ion channels found in a range of eukaryotic species including humans but are not naturally present in the yeast Saccharomyces cerevisiae. We demonstrate the first recombinant expression and functional gating of the P2X2 receptor in baker's yeast. We leverage the yeast host for facile genetic screens of mutant P2X2 by performing site saturation mutagenesis at residues of interest, including SNPs implicated in deafness and at residues involved in native binding. Deep mutational analysis and rounds of genetic engineering yield mutant P2X2 F303Y A304W, which has altered ligand selectivity toward the ATP analog AMP-PNP. The F303Y A304W variant shows over 100-fold increased intracellular calcium amplitudes with AMP-PNP compared to the WT receptor and has a much lower desensitization rate. Since AMP-PNP does not naturally activate P2X receptors, the F303Y A304W P2X2 may be a starting point for downstream applications in chemogenetic cellular control. Interestingly, the A304W mutation selectively destabilizes the desensitized state, which may provide a mechanistic basis for receptor opening with suboptimal agonists. The yeast system represents an inexpensive, scalable platform for ion channel characterization and engineering by circumventing the more expensive and time-consuming methodologies involving mammalian hosts.

A Humanized CB1R Yeast Biosensor Enables Facile Screening of Cannabinoid Compounds.

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.

Changes in Body Composition and Athletic Performance in National Collegiate Athletic Association Division I Female Field Hockey Athletes Throughout a Competitive Season.

ABSTRACT: Summer, LC, Cheng, R, Moran, JT, Lee, M, Belanger, AJ, TaylorIV, WL, and Gardner, EC. Changes in body composition and athletic performance in National Collegiate Athletic Association Division I female field hockey athletes throughout a competitive season. J Strength Cond Res 38(1): 146-152, 2024-The purposes of this study were (a) to analyze the changes in total and regional body composition measurements in a National Collegiate Athletic Association (NCAA) Division I female field hockey team throughout a 17-game competitive season using dual X-ray absorptiometry (DXA); (b) to examine improvements, if any, in athletic performance measures after a season; and (c) to report on the relationship between these body composition changes and changes in athletic performance. Preseason and postseason dual-energy DXA and performance data from the 2019-2020 season were retrospectively identified for 20 field players (forwards, midfielders, and defenders). Body composition data included total and regional fat mass, lean mass, and body fat percentage, whereas athletic performance measures included the vertical jump, 10-yard dash, and pro-agility (5-10-5) shuttle run. All variables were quantitative and analyzed using paired t -tests or its nonparametric equivalent and an alpha level of p < 0.05 was used to determine significance. After a competitive season, athletes had significant decreases in fat mass and increases in lean mass in their arms, legs, trunks, gynoids, and total body measurements. Android fat mass and body fat percentage also decreased. Athletes performed significantly better on the pro-agility shuttle run at the end of the season, but no significant differences were observed in other performance metrics. Moderate correlations were observed between changes in body composition (total fat mass and total lean mass) and changes in athletic performance. Our study provides a novel, longitudinal assessment of body composition and athletic performance for elite female field hockey athletes that will help trainers and coaches better understand how these variables change throughout a season and allow them to better prepare their players for competitive success.

Injury patterns and risk factors for orthopaedic trauma from snowboarding and skiing: a national perspective.

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.

The epidemiology of back/neck/spine injuries in National Collegiate Athletic Association men's and women's ice hockey, 2009/2010 to 2014/2015.

This study describes the epidemiology of back/neck/spine injuries in National Collegiate Athletic Association (NCAA) men's and women's ice hockey. Data from 66 NCAA men's and 29 women's ice hockey programmes (total of 147 and 67 team-seasons, respectively) were analysed from the NCAA Injury Surveillance Program during the 2009/2010-2014/2015 academic years. In the study period, 226 and 97 back/neck/spine injuries were reported in men and women, respectively, for injury rates of 0.56 and 0.65/1000 athlete exposures. Injury rates were higher in competitions than practices in men (injury rate ratio [IRR] = 4.22; 95% confidence interval [CI]: 3.24-5.49) and women (IRR = 2.49; 95% CI: 1.67-3.70). Most injuries occurred in the lower back/lumbar spine (men: 52.2%; women: 48.5%). There were notably low rates of fractures and severe spinal injuries for both sexes. This study enhances our understanding of the incidence, mechanisms and factors influencing these injuries and can ultimately lead to more effective injury prevention.

Telerehabilitation to Address the Rehabilitation Gap in Anterior Cruciate Ligament Care: Survey of Physical Therapists/Care Providers.

Background: While the importance of structured rehabilitation following anterior cruciate ligament reconstruction (ACLR), particularly in the return-to-sport phase, is known, for most patients, supervised physical therapy is often completed before this time point. The recent emergence of telerehabilitation and other digital health interventions has the potential to address this "rehabilitation gap." Methods: The study was conducted as a cross-section, online survey collecting qualitative and quantitative data from open and closed questions. Inclusion criteria included local qualified physical therapists or other professionals working with ACLR patients. Results: Eighty-three percent of respondents experienced a "rehabilitation gap" with their ACLR patients. Few reported currently utilizing apps or websites (9.74%). The majority (41/58) reported experience with telerehabilitation, and 84% felt that there was a role for digital rehabilitation strategies to address the "rehabilitation gap." The vast majority (94.74%) of participants felt that standard commercial insurance did not permit sufficient rehabilitation. Discussion: While the majority of our respondents acknowledged the existence of a "rehabilitation gap," as well as familiarity with and confidence in telerehabilitation, few were using this technique at the time of our survey. This suggests an opportunity for development in this space.

Describing the women of orthopaedic surgery.

Aims: The purpose of this survey study was to examine the demographic and lifestyle factors of women currently in orthopaedic surgery. Methods: An electronic survey was conducted of practising female orthopaedic surgeons based in the USA through both the Ruth Jackson Society and the online Facebook group "Women of Orthopaedics". Results: The majority of surveyed female orthopaedic surgeons reported being married (76.4%; 285/373) and having children (67.6%; 252/373). In all, 66.5% (247/373) were collegiate athletes; 82.0% (306/373) reported having no female orthopaedic surgeon mentors in undergraduate and medical school. Their mean height is 65.8 inches and average weight is 147.3 lbs. Conclusion: The majority of female orthopaedic surgeons did not have female mentorship during their training. Additionally, biometrically, their build is similar to that of the average American woman.

Orthopaedic Injury Patterns Related to Ice Skating, Inline Skating, and Roller Skating: A 20-Year Epidemiologic Analysis.

Background: Ice skating, inline skating, and roller skating are popular sports in the United States (US). Although they are similar, injuries incurred may be distinct and may have evolved over time. Purpose: To characterize injuries related to ice skating, inline skating, and roller skating and track injury patterns over a 20-year period. Study Design: Descriptive epidemiology study. Methods: The current study utilized the National Electronic Injury Surveillance System, a database reporting consumer product-related injuries seen at emergency departments in the US. All ice skating, inline skating, and roller skating injuries between 2002 and 2021 were identified, and patient demographics, types of injury, and year of injury were compared between skating types. Results: A total of 1,656,746 skating-related injuries were estimated nationally: 24% (403,791) for ice skating, 24% (400,172) for inline skating, and 52% (852,783) for roller skating. While the incidence of ice-skating- and roller-skating-related injuries decreased by 34.4% (from 22,490 in 2002-2004 to 14,758 in 2019-2021) and 29.6% (from 42,452 in 2002-2004 to 31,980 in 2019-2021), respectively, injuries related to inline skating decreased comparatively more, by 75.8% over the study period (from 48,097 in 2002-2004 to 11,662 in 2019-2021). Injuries occurred predominantly to the head/face/neck for ice skating (n = 139,501; 34.5% of injuries), whereas injuries occurred predominantly in the shoulder/arm/elbow/wrist for inline skating (n = 212,088, 53.0% of injuries) and roller skating (n = 425,216, 49.9% of injuries). Fracture was the most common injury type for all 3 skating types (n = 614,853, 37.1% of injuries), and the majority of fractures occurred in the upper extremity (shoulder/arm/elbow/wrist) for all 3 skating types (n = 59,624, 60.0% [ice skating]; n = 69,197, 41.2% [inline skating], and n = 237,099, 68.2% [roller skating]). Lower extremity (leg/knee/ankle) fractures were more common among ice skating (n = 28,019, 28.2%) and roller skating (n = 82,094, 23.6%) injuries compared with inline skating (n = 21,391, 12.7%). Conclusion: In the current study, we found that fractures were the most common type of injury regardless of skating type but that the location of the injury/fracture varied by skating type.

An Epidemiological Study of Cell Phone-Related Injuries of the Hand and Wrist Reported in United States Emergency Departments From 2011 to 2020.

Purpose: Increasing ownership and use of mobile phones has been recently linked to reports of hand and wrist pain from overuse, as well as more serious injuries related to distracted behaviors, such as falls and texting while driving. We describe the epidemiology of hand and wrist injuries presenting to US emergency departments from 2011 to 2020, which were associated with cell phone use using the Consumer Product Safety Commission's National Electronic Injury Surveillance System. Methods: The National Electronic Injury Surveillance System database was queried for treatment records from 2011 through to 2020 for all cell phone-related injuries of the lower arm, wrist, hand, and fingers. Using parameters provided by the National Electronic Injury Surveillance System database, there were 1,213 unique cases, yielding a total weighted estimate of 50,487 national cases presenting to emergency departments in the United States. Results: Between 2011 and 2020, the weighted estimate of annual cell phone-related injuries ranged from 3,389 to 7,320 cases. Falls were the most common cause of injury, accounting for 29.8% of estimated cases. The most common types of injuries were lacerations (22.3%). The national estimate of cell phone-related injury was the highest in the age range of 11-20 years (26.4%), followed by 21-30 years (22.2%). Women were affected more frequently than men (59.6% vs 40.4%). Conclusions: Upper extremity injuries related to cell phone use represent an increasing burden of disease to the US healthcare system. Raising awareness regarding cell phone-related injuries and in-home fall-prevention strategies, especially among elderly individuals, should be considered as means of decreasing the number of such injuries. Strategies for decreasing the burden of cell phone-related injuries occurring as a result of falls among teenagers and young adults should focus on minimizing distractions while using a cell phone. Limitations of the study include inaccuracies related to probability-weighted case estimation and limitations in reporting injuries. Clinical relevance: Knowledge of the burden of upper extremities injuries associated with this common handheld device can help to both raise awareness of this issue, as well as to potentially inform injury-prevention strategies.

Bucket-Handle Meniscus Tear Management With Meniscectomy Versus Repair Correlates With Patient, Socioeconomic, and Hospital Factors.

INTRODUCTION: Bucket-handle meniscus tears are common knee injuries that are often treated surgically with meniscectomy or meniscal repair. Although clinical factors may influence the choice of one treatment approach over the other, the influence of patient, socioeconomic, and hospital factors remains poorly characterized. This study aimed to estimate the relative nationwide utilization of these two procedures and delineate a variety of factors that are associated with the selection of one treatment approach over the other. METHODS: Meniscal repair and meniscectomy procedures conducted for isolated bucket-handle meniscus tears in 2016 and 2017 were identified in the Nationwide Ambulatory Surgery Sample database. Cases were weighted using nationally representative discharge weights. Univariate analyses and a multivariable logistic regression model were used to compare patient, socioeconomic, and hospital factors associated with meniscal repair versus meniscectomy. RESULTS: In total, 12,239 cases were identified, which represented 17,236 cases after weighting. Of these, meniscal repair was conducted for 4,138 (24.0%). Based on the logistic regression model, meniscal repair was less likely for older and sicker patients. By contrast, several factors were associated with markedly higher odds of undergoing meniscal repair compared with meniscectomy. These included urban teaching hospitals; geographic location in the midwest, south, and west; and higher median household income. DISCUSSION: Using a large nationally representative cohort, the current data revealed that only 24.0% of surgically treated bucket-handle meniscus tears were treated using repair. Identification of patient, socioeconomic, and hospital factors differentially associated with meniscal repair suggest that other factors may systematically influence surgical decision-making for this patient population. Surgeons should be conscious of these potential healthcare disparities when determining the optimal treatment for their patients. LEVEL OF EVIDENCE: Level III.

Previous Isolated Medial Bucket-Handle Meniscus Repair Significantly Increases Risk of Subsequent Ipsilateral Anterior Cruciate Ligament Reconstruction.

Purpose: (1) To define the incidence of surgically treated isolated bucket-handle meniscus tears (BHMTs); (2) to investigate risk of subsequent ipsilateral anterior cruciate ligament reconstruction (ACLR) in patients who underwent previous isolated bucket handle (BH) meniscus repair; and (3) to investigate the risk of subsequent ACLR for various types of surgically treated meniscal tears. Methods: A retrospective review of a national database was conducted to identify patients, aged 10 to 40 years, who underwent primary isolated BH meniscus surgery from 2015 to 2020. Patients were stratified by operative method. A control group of 500,000 age-matched patients was randomly selected to establish a benchmark rate of ACLR. Kaplan-Meier analysis was performed to compare the timing and incidence of subsequent ipsilateral ACLR after primary isolated BH meniscus surgery to the control group within 2 and 5 years. Results: In total, 1,767 patients with isolated BHMTs treated with surgery were identified and met inclusion criteria. The incidence of isolated BHMTs among all surgically treated (repair or meniscectomy) meniscal injuries was 1.67%. Isolated BH repairs had significantly greater odds of ACLR within 5 years compared to the control group (odds ratio [OR] 6.09; 95% confidence interval [CI] 2.86-12.99; P < .001). Medial BH repairs had the greatest odds of ACLR within 5 years (OR 9.15; 95% CI 4.27-19.57; P < .001). Lateral BH repair was not associated with subsequent ipsilateral ACLR within 5 years (OR 2.63; CI 0.37-18.90; P = .340). Conclusions: Isolated BHMTs comprised 1.67% of all surgically treated meniscal injuries. Patients who underwent prior surgery for isolated BHMT were at increased risk of undergoing subsequent ipsilateral ACLR compared with the general population. Isolated medial BHMTs treated with repair had the highest risk for subsequent ACLR. Level of Evidence: Level III, retrospective cohort study.

SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.

Coronal Malalignment-When and How to Perform a Tibial Tubercle Osteotomy.

Coronal malalignment of the patellofemoral joint may contribute to both instability as well as pain and joint overload. The use of distal realignment procedures has evolved to include uniplanar and multiplanar osteotomies, which allows patient-specific treatment. With a careful understanding of the complex pathoanatomy, including osseous, soft tissue, and dynamic muscular factors, an appropriately designed tibial tubercle osteotomy (TTO) is an invaluable tool for the orthopedic surgeon to improve joint biomechanics and off-load articular injuries. Current techniques have improved TTO surgery to limit complications and produce reliably good results.

Resistance Training as Treatment for Sarcopenia: Examining Sex-Related Differences in Physiology and Response.

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.

Epidemiology of Sports-Related Traumatic Hip Dislocations Reported in United States Emergency Departments, 2010-2019.

Background: Traumatic hip dislocations are rare injuries that most commonly occur in motor vehicle accidents. There is a paucity of literature that describes sports-related hip dislocations. Purpose: To estimate the incidence of sports-related hip dislocations and determine any sport- or sex-related epidemiological trends using the National Electronic Injury Surveillance System (NEISS) database. Study Design: Descriptive epidemiology study. Methods: Data regarding sports-related hip dislocations from 2010 to 2019 were retrieved from the NEISS, a database that catalogs injury information during emergency department visits from 100 hospitals across the United States to produce nationwide estimates of the injury burden. The estimated number of injuries was calculated using weights assigned by the NEISS database. The injuries were then stratified by sport and sex to determine any epidemiological patterns. Results: A total of 102 hip dislocation injuries were identified over the surveyed 10 years, indicating 2941 estimated injuries nationwide. Overall, 10 (9.8%) of 102 sports-related hip dislocations presented with concomitant acetabular fractures, representing an estimated 288 injuries nationally over 10 years. Male athletes sustained more sports-related hip dislocations than female athletes, with a relative incidence of 12.51 (P < .001). Adolescents aged 15 to 19 years recorded the highest number of hip dislocations. There were 17 sports identified as having caused at least 1 hip dislocation over the 10-year period. More hip dislocation injuries were sustained from contact sports (91.2%) than noncontact sports (8.8%) (P < .001). Football (estimated 164 injuries per year; 55.6%), snowboarding (28 per year; 9.5%), skiing (26 per year; 8.8%), and basketball (21 per year; 7.1%) had the highest rates of hip dislocation. Additionally, 43 (82.7%) football-related injuries were caused by tackling mechanisms, and 9 (17.3%) were caused by nontackling mechanisms (P < .001). Conclusion: The incidence of traumatic sports-related hip dislocations was extremely low in the United States during the study period. Male adolescents, aged 15 to 19 years, sustained the greatest number of injuries during football. Significantly more hip dislocations occurred in contact sports, most commonly football, snowboarding, skiing, and basketball, compared with noncontact sports. As adolescent athletes may have limited treatment options if osteonecrosis occurs, these data serve to increase the clinical awareness of these injuries.

Orthogonal control of gene expression in plants using synthetic promoters and CRISPR-based transcription factors.

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.

Patient Demographic and Socioeconomic Factors Associated With Physical Therapy Utilization After Uncomplicated Meniscectomy.

INTRODUCTION: The extent to which physical therapy (PT) is used after meniscectomy is unknown. The objective of this study was to estimate the extent to which PT is implemented after meniscectomy and to identify factors associated with its utilization. METHODS: The Mariner PearlDiver database was queried to identify patients who underwent uncomplicated meniscectomy. The number of PT visits for each patient was tabulated. Logistic regressions were used to compare demographic factors associated with no use of PT and use of nine or more PT visits. RESULTS: In total, 92,291 patients met inclusion criteria. Of these patients, 72.21% did not use PT and 27.8% used 1 or more PT visits. Of the patients who used PT, 19.76% had 1 to 8 PT visits and 8.03% had 9 or more PT visits. Older age and noncommercial insurance types were associated with no PT use. Male sex, Medicaid, and Medicare were associated with markedly lower odds of increased PT utilization. CONCLUSION: PT is used in the minority of the time after meniscectomy. Among patients who do use PT, however, notable variation exists in the amount of PT visits used. Patient age, sex, insurance status, and geographic variables were independently associated with PT utilization.

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.

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.

Sex- and Sports-Specific Epidemiology of Traumatic Lumbar Spine Injuries Sustained During Sporting Activities: Male Snowboarders and Female Horseback Riders at Greatest Risk.

PURPOSE: To generate national estimates of sports-related traumatic lumbar spine injury incidence rates using the National Electronic Injury Surveillance System (NEISS) database and determine any sports- and sex-specific epidemiologic patterns of these traumatic injuries. METHODS: Data regarding traumatic lumbar spine injuries sustained through sporting activities from 2009 to 2018 were extracted from the NEISS, a database generating nationwide estimates through patient information collected during emergency department visits from 100 NEISS hospitals across the United States. The estimated number of injuries was calculated using weights assigned by the NEISS database depending on the geographic location of the injury. RESULTS: A total of 497 traumatic lumbar spine injuries were identified over the course of 10 years, suggesting 19,208 estimated injuries. The estimated average injury rate was 6.1 injuries per million persons per year. When analyzed by sex, the incidence rate of traumatic lumbar spine injury was 3.6 injuries per million persons per year for male patients and 2.5 injuries per million persons per year for female patients (P = .663). In male patients, 47% of the injuries occurred in individuals aged between 10 and 29 years, whereas injuries in female patients were more equally distributed across different age groups. Horseback riding (27%), skiing (5%), and roller skating (4%) were the leading causes of traumatic lumbar injuries in female patients. In male patients, most injuries were experienced as a result of snowboarding (13%), weightlifting (10%), and football (6%). CONCLUSIONS: From 2009 to 2018, the estimated incidence of sports-associated traumatic lumbar spine injuries was approximately 6.1 injuries per million persons per year. Male patients experienced a greater number of traumatic lumbar injuries (3.60) than female patients (2.46), with a relative incidence rate of 1.46. The most common source of injury was snowboarding in male patients and horseback riding in female patients. LEVEL OF EVIDENCE: Level III, retrospective comparative study.