A General Approach to Activate Second-Scale Room Temperature Photoluminescence in Organic Small Molecules.

Organic small molecules that exhibit second-scale phosphorescence at room temperature are of interest for potential applications in sensing, anticounterfeiting, and bioimaging. However, such materials systems are uncommon-requiring millisecond to second-scale triplet lifetimes, efficient intersystem crossing, and slow rates of nonradiative recombination. Here, a simple and scalable approach is demonstrated to activate long-lived phosphorescence in a wide variety of molecules by suspending them in rigid polymer hosts and annealing them above the polymer's glass transition temperature. This process produces submicron aggregates of the chromophore, which suppresses intramolecular motion that leads to nonradiative recombination and minimizes triplet-triplet annihilation that quenches phosphorescence in larger aggregates. In some cases, evidence of excimer-mediated intersystem crossing that enhances triplet generation in aggregated chromophores is found. In short, this approach circumvents the current design rules for long-lived phosphors, which will streamline their discovery and development.

Role for DPP4 inhibitor therapy in cystic fibrosis related diabetes: A single centre experience.

INTRODUCTION: Insulin remains the only recommended medical treatment for cystic fibrosis related diabetes (CFRD) Whilst there is an established role for orally bioavailable incretin mimetic agents such as the dipeptidyl peptidase-4 inhibitors (DPP4-I) in Type 2 diabetes mellitus, there exists little data on their utility in CFRD. AIM: To examine the use of DPP4-I therapy in patients with CFRD at a single large adult cystic fibrosis center. METHOD: People with CFRD prescribed a DPP4-I were identified from our specialist CFRD clinic and records were retrospectively examined for indication for therapy, tolerability and effectiveness. Analysis of continuous glucose monitoring data Libre 2 was done for these patients (CGM) pre and at least 3 months post therapy was performed. RESULTS: 23 people with CF (PwCF) with a mean (SD) age of 35.0 ± 2.4 years were included in this analysis . In 21 patients DPP4-I was prescribed as a monotherapy and it was given in combination with insulin in 2 others. Indications for therapy included reactive hypoglycaemia (n = 10) post prandial hyperglycaemia (8), insulin avoidance (3), metformin intolerance (1) and unclear (1). Therapy was well tolerated with no discontinuations due to adverse effects. Significant improvements were noted in Time in Range- Pre vs Post: 78.0 [67.5 - 84.0] vs 89.0 [79.8 - 96.0]%, p = 0.005, Time above Range -Pre vs Post: 19.5 [12.5 - 30.8] vs 6.0 [2.5 - 16.5]%, p = 0.006 and glucose variability Pre versus Post: 28.3 [25.4 - 31.1] vs 26.9 [23.1 - 31.3], p = 0.021, Of the 10 subjects who initiated therapy for hypoglycaemia, 7 reported an improvement in symptoms. No significant difference was found in weight pre and post: 61.5 ± 15.0 kg vs 62.5 ± 15.3 kg, p = 0.326 or Hba1c pre vs post: 41.0 [36.0 - 53.3] mmol/mol versus 40.5 [36.8 - 47.3], p = 0.727. CONCLUSION: DPP4-I is well tolerated in CFRD and can lead to an improved glycaemic control in these patients with significant improvement in validated CGM metrics.

A Sb(III)-specific efflux transporter from Ensifer adhaerens E-60.

Antimony is pervasive environmental toxic substance, and numerous genes encoding mechanisms to resist, transform and extrude the toxic metalloid antimony have been discovered in various microorganisms. Here we identified a major facilitator superfamily (MFS) transporter, AntB, on the chromosome of the arsenite-oxidizing bacterium Ensifer adhaerens E-60 that confers resistance to Sb(III) and Sb(V). The antB gene is adjacent to gene encoding a LysR family transcriptional regulator termed LysRars, which is an As(III)/Sb(III)-responsive transcriptional repressor that is predicted to control expression of antB. Similar antB and lysRars genes are found in related arsenic-resistant bacteria, especially strains of Ensifer adhaerens, and the lysRars gene adjacent to antB encodes a member of a divergent subgroup of putative LysR-type regulators. Closely related AntB and LysRars orthologs contain three conserved cysteine residues, which are Cys17, Cys99, and Cys350 in AntB and Cys81, Cys289 and Cys294 in LysRars, respectively. Expression of antB is induced by As(III), Sb(III), Sb(V) and Rox(III) (4-hydroxy-3-nitrophenyl arsenite). Heterologous expression of antB in E. coli AW3110 (Δars) conferred resistance to Sb(III) and Sb(V) and reduced the intracellular concentration of Sb(III). The discovery of the Sb(III) efflux transporter AntB enriches our knowledge of the role of the efflux transporter in the antimony biogeochemical cycle.

Discovery of Crystallizable Organic Semiconductors with Machine Learning.

Crystalline organic semiconductors are known to have improved charge carrier mobility and exciton diffusion length in comparison to their amorphous counterparts. Certain organic molecular thin films can be transitioned from initially prepared amorphous layers to large-scale crystalline films via abrupt thermal annealing. Ideally, these films crystallize as platelets with long-range-ordered domains on the scale of tens to hundreds of microns. However, other organic molecular thin films may instead crystallize as spherulites or resist crystallization entirely. Organic molecules that have the capability of transforming into a platelet morphology feature both high melting point (Tm) and crystallization driving force (ΔGc). In this work, we employed machine learning (ML) to identify candidate organic materials with the potential to crystallize into platelets by estimating the aforementioned thermal properties. Six organic molecules identified by the ML algorithm were experimentally evaluated; three crystallized as platelets, one crystallized as a spherulite, and two resisted thin film crystallization. These results demonstrate a successful application of ML in the scope of predicting thermal properties of organic molecules and reinforce the principles of Tm and ΔGc as metrics that aid in predicting the crystallization behavior of organic thin films.

Preventing Exertional Heat Stroke in Football: Time for a Paradigm Shift.

CONTEXT: Among American sports, football has the highest incidence of exertional heat stroke (EHS), despite decades of prevention strategies. Based on recent reports, 100% of high school and college EHS football fatalities occur during conditioning sessions. Linemen are the at-risk population, constituting 97% of football EHS deaths. Linemen heat up faster and cool down slower than other players. EVIDENCE ACQUISITION: Case series were identified from organized, supervised football at the youth, high school, and collegiate levels and compiled in the National Registry of Catastrophic Sports Injuries. Sources for event occurrence were media reports and newspaper clippings, autopsy reports, certificates of death, school-sponsored investigations, and published medical literature. Articles were identified through PubMed with search terms "football," "exertional heat stroke," and "prevention." STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Football EHS is tied to (1) high-intensity drills and conditioning that is not specific to individual player positions, (2) physical exertion as punishment; (3) failure to modify physical activity for high heat and humidity, (4) failure to recognize early signs and symptoms of EHS, and (5) death when cooling is delayed. CONCLUSION: To prevent football EHS, (1) all training and conditioning should be position specific; (2) physical activity should be modified per the heat load; (3) understand that some players have a "do-or-die" mentality that supersedes their personal safety; (4) never use physical exertion as punishment; (5) eliminate conditioning tests, serial sprints, and any reckless drills that are inappropriate for linemen; and (6) consider air-conditioned venues for linemen during hot practices. To prevent EHS, train linemen based on game demands. STRENGTH-OF-RECOMMENDATION TAXONOMY: n/a.

Arsenate reductase of Rufibacter tibetensis is a metallophosphoesterase evolved to catalyze redox reactions.

An arsenate reductase (Car1) from the Bacteroidetes species Rufibacter tibetensis 1351T was isolated from the Tibetan Plateau. The strain exhibits resistance to arsenite [As(III)] and arsenate [As(V)] and reduces As(V) to As(III). Here we shed light on the mechanism of enzymatic reduction by Car1. AlphaFold2 structure prediction, active site energy minimization, and steady-state kinetics of wild-type and mutant enzymes give insight into the catalytic mechanism. Car1 is structurally related to calcineurin-like metallophosphoesterases (MPPs). It functions as a binuclear metal hydrolase with limited phosphatase activity, particularly relying on the divalent metal Ni2+. As an As(V) reductase, it displays metal promiscuity and is coupled to the thioredoxin redox cycle, requiring the participation of two cysteine residues, Cys74 and Cys76. These findings suggest that Car1 evolved from a common ancestor of extant phosphatases by incorporating a redox function into an existing MPP catalytic site. Its proposed mechanism of arsenate reduction involves Cys74 initiating a nucleophilic attack on arsenate, leading to the formation of a covalent intermediate. Next, a nucleophilic attack of Cys76 leads to the release of As(III) and the formation of a surface-exposed Cys74-Cys76 disulfide, ready for reduction by thioredoxin.

Seafloor macrolitter as a settling platform for non-native species: A case study from UK waters.

Marine litter is increasingly recognised as a vector for the spread of non-native species (NNS). However, our understanding of its role in the propagation of NNS in UK waters remains limited. As part of the Clean Seas Environmental Monitoring Programme, we opportunistically analysed seafloor macrolitter items trawled from various locations around the coast of England and Wales and examined each for the presence of NNS. Of the 41 litter items analysed, we identified a total of 133 taxa, including two non-native and four cryptogenic species. This confirms that NNS are settling on seafloor macrolitter in UK waters and that these can be detected using morphological taxonomic analysis. Furthermore, we propose a methodology to classify litter based on size, rugosity and polymer/material type to explore whether there were detectable patterns governing community composition and litter characteristics. This exploratory investigation provides evidence to inform future risk assessments of NNS vectors and pathways.

A Haemophilus ducreyi strain lacking the yfeABCD iron transport system is virulent in human volunteers.

Haemophilus ducreyi causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host, H. ducreyi expresses a TonB-dependent hemoglobin receptor, HgbA, which is necessary and sufficient for H. ducreyi to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by H. ducreyi in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HPΔyfeABΔyfeCD, which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HPΔyfeABΔyfeCD-inoculated sites (P = 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites (P = 0.79). Thus, the ABC transporter encoded by yfeAB and yfeCD was dispensable for H. ducreyi virulence in humans. In the absence of YfeABCD, H. ducreyi likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.

Anticancer Effects of the Trivalent Organoarsenical 2-Amino-4-(dihydroxyarsinoyl) Butanoate.

According to the National Cancer Institute, breast cancer is a leading cause of death in women. The lack of progesterone and estrogen receptors in triple-negative breast cancer (TNBC) cells results in a lack of response to hormonal, monoclonal, or tyrosine kinase inhibitor therapies. Despite intensive drug discovery, there is still no approved targeted treatment for TNBC. The metalloid arsenic has been used in herbal medicines, antibiotics, and chemotherapeutic drugs for centuries. This paper demonstrates that a trivalent arsenic-containing, nonproteogenic amino acid, R-AST-OH (2-amino-4-(dihydroxyarsinoyl) butanoate), inhibits kidney-type glutaminase (KGA), the enzyme that controls glutamine metabolism and is correlated with tumor malignancy. Cell-based assays using the TNBC MDA-MB-231 and HCC1569 cell lines showed that R-AST-OH kills TNBC cells and is not cytotoxic to a control cell line. The results of in silico molecular docking predictions indicate that R-AST-OH binds to the glutamine binding site and forms a covalent bond with an active site cysteine residue. We hypothesize that R-AST-OH is a single warhead for KGA that irreversibly binds to KGA through the formation of an As-S bond. We propose that R-AST-OH is a promising lead compound for the design of new drugs for the treatment of TNBC.

The Importance of Medial Patellar Shape as a Risk Factor for Recurrent Patellar Dislocation in Adults.

BACKGROUND: Research on the cause of lateral patellar dislocation (LPD) has focused on trochlear morphologic parameters, joint alignment, and patellofemoral soft tissue forces. A paucity of information is available regarding how patellar morphologic parameters influence the risk for LPD. PURPOSE/HYPOTHESIS: The purpose was to assess whether patellar morphology is a risk factor for recurrent LPD. It was hypothesized that (1) patients with recurrent LPD would have decreased patellar width and volume and (2) patellar morphologic parameters would accurately discriminate patients with recurrent LPD from controls. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A total of 21 adults with recurrent LPD (age, 29.7 ± 11.1 years; height, 170.8 ± 9.9 cm; weight, 76.1 ± 17.5 kg; 57% female) were compared with 21 sex- and height-matched controls (age, 27.2 ± 6.7 years; height, 172.0 ± 10.6 cm; weight, 71.1 ± 12.8 kg; 57% female). Three-dimensional axial fat-saturated magnetic resonance imaging scans were used to measure patellar medial, lateral, and total width; patellar volume; patellar medial and lateral facet length; the Wiberg index; and previously validated knee joint alignment and femoral shape measurements (eg, tibial tuberosity to trochlear groove distance, trochlear dysplasia). RESULTS: The LPD group demonstrated reduced medial patellar width (Δ = -3.6 mm; P < .001) and medial facet length (Δ = -3.7 mm; P < .001) but no change in lateral width or facet length. This resulted in decreased total patellar width (Δ = -3.2 mm; P = .009), decreased patellar volume (Δ = -0.3 cm3; P = .025), and an increased Wiberg index (Δ = 0.05; P < .001). No significant differences were found for all other patellar shape measures between cohorts. Medial patellar width was the strongest single discriminator (83.3% accuracy) for recurrent LPD. Combining medial patellar width, patellofemoral tilt, and trochlear groove length increased the discrimination to 92.9%. CONCLUSION: The medial patellar width was significantly smaller in patients with recurrent LPD and was the single most accurate discriminator for recurrent LPD, even compared with traditional trochlear shape and joint alignment measures (eg, trochlear dysplasia, patella alta). Therefore, medial patellar morphology should be assessed in patients with LPD as a risk factor for recurrence and a potential means to improve treatment.

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

Cervical cancer management in a low resource setting: A 10-year review in a tertiary care hospital in Kenya.

Background: Cervical cancer is one of the leading causes of cancer mortality among women in Kenya due to late presentations, poor access to health care, and limited resources. Across many low- and middle-income countries infrastructure and human resources for cervical cancer management are currently insufficient to meet the high population needs therefore patients are not able to get appropriate treatment. Objective: This study aimed to describe the clinicopathological characteristics and the treatment profiles of cervical cancer cases seen at Moi Teaching and Referral Hospital (MTRH). Methods: This was a retrospective cross-sectional study conducted at MTRH involving the review of the electronic database and medical charts of 1541 patients with a histologically confirmed diagnosis of cervical cancer between January 2012 and December 2021. Results: Of the 1541 cases analyzed, 91% were squamous cell carcinomas, 8% were adenocarcinomas, and 1% were other histological types. Thirty-eight percent of the patients were HIV infected and less than 30% of the women had health insurance. A majority (75%) of the patients presented with advanced-stage disease (stage IIB-IV). Only 13.9% received chemoradiotherapy with curative intent; of which 33.8% received suboptimal treatment. Of the 13% who received surgical treatment, 45.3% required adjuvant therapy, of which only 27.5% received treatment. Over 40% of the women were lost to follow-up. Conclusion: Most of the patients with cervical cancer in Kenya present at advanced stages with only a third receiving the necessary treatment while the majority receive only palliative treatment or supportive care.

Sublimed C60 for efficient and repeatable perovskite-based solar cells.

Thermally evaporated C60 is a near-ubiquitous electron transport layer in state-of-the-art p-i-n perovskite-based solar cells. As perovskite photovoltaic technologies are moving toward industrialization, batch-to-batch reproducibility of device performances becomes crucial. Here, we show that commercial as-received (99.75% pure) C60 source materials may coalesce during repeated thermal evaporation processes, jeopardizing such reproducibility. We find that the coalescence is due to oxygen present in the initial source powder and leads to the formation of deep states within the perovskite bandgap, resulting in a systematic decrease in solar cell performance. However, further purification (through sublimation) of the C60 to 99.95% before evaporation is found to hinder coalescence, with the associated solar cell performances being fully reproducible after repeated processing. We verify the universality of this behavior on perovskite/silicon tandem solar cells by demonstrating their open-circuit voltages and fill factors to remain at 1950 mV and 81% respectively, over eight repeated processes using the same sublimed C60 source material. Notably, one of these cells achieved a certified power conversion efficiency of 30.9%. These findings provide insights crucial for the advancement of perovskite photovoltaic technologies towards scaled production with high process yield.

Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is widely used as a host cell for recombinant protein production due to its fast growth, cost-effective culturing, and ability to secrete large and complex proteins. However, one major drawback is the relatively low yield of produced proteins compared to other host systems. To address this issue, we developed an overlay assay to screen the yeast knockout collection and identify mutants that enhance recombinant protein production, specifically focusing on the secretion of the Trametes trogii fungal laccase enzyme. Gene ontology analysis of these mutants revealed an enrichment of processes including vacuolar targeting, vesicle trafficking, proteolysis, and glycolipid metabolism. We confirmed that a significant portion of these mutants also showed increased activity of the secreted laccase when grown in liquid culture. Notably, we found that the combination of deletions of OCA6, a tyrosine phosphatase gene, along with PMT1 or PMT2, two genes encoding ER membrane protein-O-mannosyltransferases involved in ER quality control, and SKI3, which encode for a component of the SKI complex responsible for mRNA degradation, further increased secreted laccase activity. Conversely, we also identified over 200 gene deletions that resulted in decreased secreted laccase activity, including many genes that encode for mitochondrial proteins and components of the ER-associated degradation pathway. Intriguingly, the deletion of the ER DNAJ co-chaperone gene SCJ1 led to almost no secreted laccase activity. When we expressed SCJ1 from a low-copy plasmid, laccase secretion was restored. However, overexpression of SCJ1 had a detrimental effect, indicating that precise dosing of key chaperone proteins is crucial for optimal recombinant protein expression. This study offers potential strategies for enhancing the overall yield of recombinant proteins and provides new avenues for further research in optimizing protein production systems.

Facial injuries in the National Basketball Association: 2013-14 through 2017-18.

OBJECTIVE: To describe the epidemiology, mechanisms, treatment, and disability for facial injuries in National Basketball Association (NBA) athletes. METHODS: This was a retrospective descriptive epidemiological chart review using NBA Electronic Medical Record (EMR) system. Responses to injuries reported in games, practices, and other activities were used for all data analysis, except for game incidence rates. Incidence rates were calculated by the game-related facial injury incidence per total athlete exposure (player-games). RESULTS: There were 440 facial injuries among 263 athletes during the 5 NBA seasons with an overall single-season risk of 12.6% and a game incidence of 2.4 per 1000 athlete-exposures (95% CI: 2.18-2.68). The majority of injuries were lacerations (n = 159, 36.1%), contusions (n = 99, 22.5%), or fractures (n = 67, 15.2%), with ocular (n = 163, 37.0%) being the most commonly injured location. Sixty (13.6%) injuries resulted in at least one NBA game missed (224 cumulative player-games) with ocular injuries resulting in the most cumulative games missed (n = 167, 74.6%). Nasal fractures (n = 39, 58.2%) were the most common fracture location followed by ocular fractures (n = 12, 17.9%) but were less likely to lead to games missed (median = 1, IRQ: 1-3) than ocular (median = 7, IQR: 2-10) fractures. CONCLUSIONS: An average of one in eight NBA players sustained a facial injury each season with ocular injuries being the most common location. While most facial injuries are minor, serious injuries, especially ocular fractures, can result in games missed.

The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Catastrophic Sports Injuries: Causation and Prevention.

➤ Catastrophic injuries in U.S. high school and college athletes are rare but devastating injuries.➤ Catastrophic sports injuries are classified as either traumatic, caused by direct contact during sports participation, or nontraumatic, associated with exertion while participating in a sport.➤ Football is associated with the greatest number of traumatic and nontraumatic catastrophic injuries for male athletes, whereas cheerleading has the highest number of traumatic catastrophic injuries and basketball has the highest number of nontraumatic catastrophic injuries for female athletes.➤ The incidence of traumatic catastrophic injuries for all sports has declined over the past 40 years, due to effective rule changes, especially in football, pole-vaulting, cheerleading, ice hockey, and rugby. Further research is necessary to reduce the incidence of structural brain injury in contact sports such as football.➤ The incidence of nontraumatic catastrophic injuries has increased over the last 40 years and requires additional research and preventive measures. Avoiding overexertion during training, confirming sickle cell trait status in high school athletes during the preparticipation physical examination, and developing cost-effective screening tools for cardiac abnormalities are critical next steps.