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Abstract Background Chronic, low-grade inflammation provides a link between normal ageing and the pathogenesis of age-related diseases. A series of in vitro tests confirmed the strong anti-inflammatory activities of known inhibitors of NF-κB activation (δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, and dexamethasone). δ-Tocotrienol also suppresses β-hydroxy-β-methylglutaryl coenzyme A (HMG-CoA) reductase activity (the rate-limiting step in de novo cholesterol synthesis), and concomitantly lowers serum total and LDL cholesterol levels. We evaluated these compounds in an avian model anticipating that a dietary additive combining δ-tocotrienol with quercetin, riboflavin, (-) Corey lactone, amiloride, or dexamethasone would yield greater reductions in serum levels of total cholesterol, LDL-cholesterol and inflammatory markers (tumor necrosis factor-α [TNF-α], and nitric oxide [NO]), than that attained with the individual compounds. Results The present results showed that supplementation of control diets with all compounds tested except riboflavin, (-) Corey lactone, and dexamethasone produced small but significant reductions in body weight gains as compared to control. (-) Corey lactone and riboflavin did not significantly impact body weight gains. Dexamethasone significantly and markedly reduced weight gain (>75%) compared to control. The serum levels of TNF-α and NO were decreased 61% - 84% (P < 0.001), and 14% - 67%, respectively, in chickens fed diets supplemented with δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, or dexamethasone as compared to controls. Significant decreases in the levels of serum total and LDL-cholesterol were attained with δ-tocotrienol, quercetin, riboflavin and (-) Corey lactone (13% - 57%; P < 0.05), whereas, these levels were 2-fold higher in dexamethasone treated chickens as compared to controls. Parallel responses on hepatic lipid infiltration were confirmed by histological analyses. Treatments combining δ-tocotrienol with the other compounds yielded values that were lower than individual values attained with either δ-tocotrienol or the second compound. Exceptions were the significantly lower total and LDL cholesterol and triglyceride values attained with the δ-tocotrienol/(-) Corey lactone treatment and the significantly lower triglyceride value attained with the δ-tocotrienol/riboflavin treatment. δ-Tocotrienol attenuated the lipid-elevating impact of dexamethasone and potentiated the triglyceride lowering impact of riboflavin. Microarray analyses of liver samples identified 62 genes whose expressions were either up-regulated or down-regulated by all compounds suggesting common impact on serum TNF-α and NO levels. The microarray analyses further identified 41 genes whose expression was differentially impacted by the compounds shown to lower serum lipid levels and dexamethasone, associated with markedly elevated serum lipids. Conclusions This is the first report describing the anti-inflammatory effects of δ-tocotrienol, quercetin, riboflavin, (-) Corey lactone, amiloride, and dexamethasone on serum TNF-δ and NO levels. Serum TNF-δ levels were decreased by >60% by each of the experimental compounds. Additionally, all the treatments except with dexamethasone, resulted in lower serum total cholesterol, LDL-cholesterol and triglyceride levels. The impact of above mentioned compounds on the factors evaluated herein was increased when combined with δ-tocotrienol.

Hepatopancreatic microsporidiosis (HPM), caused by the microsporidium Ecytonucleospora hepatopenaei (EHP) leads to retarded growth and enhanced susceptibility to other diseases in shrimp resulting in a major loss for the shrimp industry worldwide. It is little understood how EHP infects its host and hijacks its cellular machinery to replicate and exert clinical manifestations in infected shrimp. Since the initial record of HPM, histopathology and polymerase chain reaction (PCR)-based assays were developed for the detection of EHP to prevent spread of the disease. Availability of an antibody-based detection method would complement these existing diagnostic tools and be useful in studying EHP pathogenesis. We describe here an immunofluorescence assay (IFA) for detecting EHP using monoclonal antibodies (mAbs) that were originally developed against Cryptosporidium parvum, a coccidian parasite that infects calves (Bos taurus), other agriculturally important animals, and humans. Forty-one mAbs were screened and two mAbs, 3E2 and 3A12, were found to detect EHP successfully. The utility of these mAbs in detecting EHP was further assessed by testing 36 experimentally challenged EHP-infected shrimp (Penaeus vannamei). EHP-detection data from infected shrimp were compared by Hematoxylin and Eosin (H&E) histology, real-time PCR, and immunofluorescence. The data show IFA using mAbs 3E2 and 3A12 could successfully detect EHP and that the sensitivity of detection is comparable to H&E histology and quantitative PCR. Availability of mAbs that can detect EHP is expected to be immensely beneficial in HPM diagnosis. Since the pathobiology of C. parvum has been so widely studied, these cross-reactive mAbs may also aid in gaining some insight into EHP pathogenesis and disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The gastrointestinal disease cryptosporidiosis, caused by the genus Cryptosporidium , is a common cause of diarrheal diseases in children, particularly in developing countries and frequently fatal in immunocompromised individuals. Cryptosporidium hominis ( Ch )-specific bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) has been a molecular target for inhibitor design. ( Note that this bifunctional enzyme has also been referred to as TS-DHFR in previous literature since the functional biochemical reaction first involves the conversion of methylene tetrahydrofolate to dihydrofolate at the TS site .) While nanomolar inhibitors of Ch DHFR-TS have been identified at the biochemical level, effective delivery of these compounds to achieve anticryptosporidial activity in cell culture and in vivo models of parasite infection remains a major challenge in developing new therapies. Previous studies, using a nanotherapy approach, have shown a promising Ch DHFR-TS inhibitor, 906, that can successfully target Cryptosporidium parasites in cell culture with nanomolar anticryptosporidial activity. This formulation utilized poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) loaded with 906 (NP-906) and conjugated with a Cryptosporidium monoclonal antibody (MAb) on the nanoparticle surface to specifically target the glycoprotein GP25-200 in excysting oocysts. However, a limitation for in vivo use is antibody susceptibility to gastric acidity. To address this gap, a prodrug diethyl ester form of 906 (MAb-NP-Prodrug) was synthesized that allowed higher compound loading in the MAb-coated PLGA nanoparticles. An oral formulation was prepared by loading lyophilized MAb-NP-Prodrug into gelatin capsules with an enteric coating for gastric stability. Proof-of-concept studies with this oral formulation demonstrated antiparasitic activity in a chronic mouse model of Cryptosporidium infection. Efficacy was observed after a low daily dose of 2 × 8 mg kg -1 for 5 days, when examined 6 and 20 days postinfection, offering a new avenue of drug delivery to be further explored., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Microplastics threaten soil ecosystems, strongly influencing carbon (C) and nitrogen (N) contents. Interactions between microplastic properties and climatic and edaphic factors are poorly understood. We conducted a meta-analysis to assess the interactive effects of microplastic properties (type, shape, size, and content), native soil properties (texture, pH, and dissolved organic carbon (DOC)) and climatic factors (precipitation and temperature) on C and N contents in soil. We found that low-density polyethylene reduced total nitrogen (TN) content, whereas biodegradable polylactic acid led to a decrease in soil organic carbon (SOC). Microplastic fragments especially depleted TN, reducing aggregate stability, increasing N-mineralization and leaching, and consequently increasing the soil C/N ratio. Microplastic size affected outcomes; those <200 μm reduced both TN and SOC contents. Mineralization-induced nutrient losses were greatest at microplastic contents between 1 and 2.5% of soil weight. Sandy soils suffered the highest microplastic contamination-induced nutrient depletion. Alkaline soils showed the greatest SOC depletion, suggesting high SOC degradability. In low-DOC soils, microplastic contamination caused 2-fold greater TN depletion than in soils with high DOC. Sites with high precipitation and temperature had greatest decrease in TN and SOC contents. In conclusion, there are complex interactions determining microplastic impacts on soil health. Microplastic contamination always risks soil C and N depletion, but the severity depends on microplastic characteristics, native soil properties, and climatic conditions, with potential exacerbation by greenhouse emission-induced climate change.

Cyanobacteria require liquid water for photosynthesis, whereas green algae can photosynthesise with water vapour alone. We discovered that several Lobaria spp. which normally have cyanobacteria as the sole photobiont, in some regions of the trans-Himalayas also harboured green algae. We tested whether green algal acquisition was: limited to high elevations; obtained from neighbouring chloro- Lobaria species; enabled photosynthesis at low humidity. Lobaria spp. were collected from 2000 to 4000 m elevation. Spectrophotometry quantified green algal abundance by measuring chlorophyll b (absent in cyanobacteria). Thalli cross-sections visually confirmed green algal presence. We sequenced gene regions: Lobaria ( ITS-EF-1α-RPB2 ), green algae ( 18S-RBC-L ) and Nostoc ( 16S ). Phylogenetic analysis determined myco-photobiont associations. We used a custom closed-circuit gas exchange system with an infrared gas analyser to measure CO 2 exchange rates for desiccated specimens at 33%, 76%, 86% and 98% humidity. Cross-sections revealed that the photobiont layers in putative cyano -Lobaria contained both cyanobacteria and green algae, indicating that they should be considered chloro-cyanolichens. Chloro- Lobaria had no visible cephalodia nor cyanobacteria in the photobiont layer. Chloro- Lobaria and chloro-cyano- Lobaria had comparable levels of chlorophyll b . Chloro- Lobaria usually contained Symbiochloris. Chloro-cyano- Lobaria mainly associated with Parachloroidium and Nostoc ; infrequently with Symbiochloris , Apatococcus, Chloroidium , Pseudochlorella, Trebouxia . Sequences from two green algal genera were obtained from within some thalli. Desiccated specimens of every Lobaria species could attain net photosynthesis with light exposure and 33% humidity. CO 2 exchange dynamics over a five-day period differed between species. At all elevations, chloro-cyano- Lobaria spp. had abundant green algae in the photobiont layer, but green algal strains mostly differed to those of chloro- Lobaria spp. Both chloro- Lobaria and chloro-cyano- Lobaria were capable of conducting photosynthesis without liquid water. The data strongly suggest that they attained positive net photosynthesis., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Climate change and other anthropogenic disturbances are increasing liana abundance and biomass in many tropical and subtropical forests. While the effects of living lianas on species diversity, ecosystem carbon, and nutrient dynamics are receiving increasing attention, the role of dead lianas in forest ecosystems has been little studied and is poorly understood. Trees and lianas coexist as the major woody components of forests worldwide, but they have very different ecological strategies, with lianas relying on trees for mechanical support. Consequently, trees and lianas have evolved highly divergent stem, leaf, and root traits. Here we show that this trait divergence is likely to persist after death, into the afterlives of these organs, leading to divergent effects on forest biogeochemistry. We introduce a conceptual framework combining horizontal, vertical, and time dimensions for the effects of liana proliferation and liana tissue decomposition on ecosystem carbon and nutrient cycling. We propose a series of empirical studies comparing traits between lianas and trees to answer questions concerning the influence of trait afterlives on the decomposability of liana and tree organs. Such studies will increase our understanding of the contribution of lianas to terrestrial biogeochemical cycling, and help predict the effects of their increasing abundance., (© 2024 John Wiley & Sons Ltd.)

Recent advances in the in vitro cultivation of Cryptosporidium parvum using hollow fiber bioreactor technology (HFB) have permitted continuous growth of parasites that complete all life cycle stages. The method provides access to all stages of the parasite and provides a method for non-animal production of oocysts for use in clinical trials. Here we examined the effect of long-term (>20 months) in vitro culture on virulence-factors, genome conservation, and in vivo pathogenicity of the host by in vitro cultured parasites. We find low-level sequence variation that is consistent with that observed in calf-passaged parasites. Further using a calf model infection, oocysts obtained from the HFB caused diarrhea of the same volume, duration and oocyst shedding intensity as in vivo passaged parasites., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yarlett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hispanic/Latinx communities remain an underserved population in terms of health and physical activity opportunities. The rise of sport specialization can jeopardize these opportunities. Understanding the appeal and welcomeness that minoritized populations feel toward sport and sport specialization culture can play an important role in health promotion and breaking down barriers that widen the gap on physical activity levels in Hispanic/Latinx communities. To date, these studies have not qualitatively investigated Hispanic/Latinx youth sport dyads (parent and child) and how sport specialization perceptions have affected their sport participation experiences. We used a qualitative interpretative phenomenological analysis to explore experiences of Hispanic/Latinx high school athletes. We engaged in semistructured interviews with 12 parent-child dyads. The following 3 interrelated themes emerged: (a) expectations of youth sport participation, (b) meeting expectations of youth sport participation, (c) and (mis)alignment of cultures. Dyads describe a negative youth sport experience when both cultures do not align because of the rise in sport specialization and pay-to-play culture. Findings indicate that dyads understand what is necessary to participate in organized sport and do this by methods that are rooted in their Hispanic/Latinx culture., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Recent advances on the development of bumped kinase inhibitors for treatment of cryptosporidiosis have focused on the 5-aminopyrazole-4-carboxamide scaffold, due to analogs that have less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, and -1708, showed strong efficacy in C. parvum infected mice. Both BKI-1770 and BKI-1841 had efficacy in the C. parvum newborn calf model, reducing diarrhea and oocyst excretion. However, both compounds caused hyperflexion of the limbs seen as dropped pasterns. Toxicity experiments in rats and calves dosed with BKI-1770 showed enlargement of the epiphyseal growth plate at doses only slightly higher than the efficacious dose. Mice were used as a screen to check for bone toxicity, by changes to the tibia epiphyseal growth plate, or neurological causes, by use of a locomotor activity box. These results showed neurological effects from both BKI-1770 and BKI-1841 and bone toxicity in mice from BKI-1770, indicating one or both effects may be contributing to toxicity. However, BKI-1708 remains a viable treatment candidate for further evaluation as it showed no signs of bone toxicity or neurological effects in mice.

Background: Adolescent athletes report that sports specialization improves their ability to receive a collegiate athletics scholarship, though this is not well-understood. The purpose of this study was to examine self-reported trends in high school specialization and influences for sport participation between Division I (D-I) and college-aged club (club) athletes., Hypothesis: There would be no difference in high school sport specialization or sport participation influences between D-I and club athletes., Study Design: Retrospective cross-sectional study., Level of Evidence: Level 3., Methods: A survey included specialization classification (low, moderate, and high) for 9th to 12th grade, age that the athlete started organized sport and his or her collegiate sport, and several influential factors for participation in one's primary high school sport (1 = no influence to 5 = extremely influential). Chi-square analyses were used to compare specialization classifications between groups. Nonparametric tests were used to determine significant differences in age-related variables and influential factors between D-I and club athletes. All analysis were also conducted with boys and girls separately., Results: Participants included 266 D-I (girls, 155; 58%) and 180 club (girls, 122; 68%) athletes. Club athletes were more likely to be classified as low specialization at every grade in high school, and this difference was more pronounced between D-I and club female athletes than male athletes. The number of years an athlete was classified as highly specialized in high school was not different between D-I and club athletes. Club athletes were more influenced by playing with friends than D-I athletes and D-I athletes were more influenced by pursuing a collegiate scholarship than club athletes., Conclusion: High levels of specialization in high school sport may not be necessary for playing at the collegiate level, though some level of specialization in high school might be necessary., Clinical Relevance: Clinicians should advocate for healthy long-term athlete development, which does not support high specialization in high school sports.

Collateral lethality occurs when loss of a gene/protein renders cancer cells dependent on its remaining paralog. Combining genome-scale CRISPR/Cas9 loss-of-function screens with RNA sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase vaccinia-related kinase 1 (VRK1) for their survival in vivo. VRK1 dependency was inversely correlated with expression of its paralog VRK2. VRK2 knockout sensitized cells to VRK1 loss, and conversely, VRK2 overexpression increased cell fitness in the setting of VRK1 loss. DNA methylation of the VRK2 promoter was associated with low VRK2 expression in human neuroblastomas and adult and pediatric gliomas. Mechanistically, depletion of VRK1 reduced barrier-to-autointegration factor phosphorylation during mitosis, resulting in DNA damage and apoptosis. Together, these studies identify VRK1 as a synthetic lethal target in VRK2 promoter-methylated adult and pediatric gliomas and neuroblastomas.

Immunotherapy with anti-GD2 antibodies has advanced the treatment of children with high-risk neuroblastoma, but nearly half of patients relapse, and little is known about mechanisms of resistance to anti-GD2 therapy. Here, we show that reduced GD2 expression was significantly correlated with the mesenchymal cell state in neuroblastoma and that a forced adrenergic-to-mesenchymal transition (AMT) conferred downregulation of GD2 and resistance to anti-GD2 antibody. Mechanistically, low-GD2-expressing cell lines demonstrated significantly reduced expression of the ganglioside synthesis enzyme ST8SIA1 (GD3 synthase), resulting in a bottlenecking of GD2 synthesis. Pharmacologic inhibition of EZH2 resulted in epigenetic rewiring of mesenchymal neuroblastoma cells and re-expression of ST8SIA1, restoring surface expression of GD2 and sensitivity to anti-GD2 antibody. These data identify developmental lineage as a key determinant of sensitivity to anti-GD2 based immunotherapies and credential EZH2 inhibitors for clinical testing in combination with anti-GD2 antibody to enhance outcomes for children with neuroblastoma., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Infection with Cryptosporidium spp. can cause severe diarrhea, leading to long-term adverse impacts and even death in malnourished children and immunocompromised patients. The only FDA-approved drug for treating cryptosporidiosis, nitazoxanide, has limited efficacy in the populations impacted the most by the diarrheal disease, and safe, effective treatment options are urgently needed. Initially identified by a large-scale phenotypic screening campaign, the antimycobacterial therapeutic clofazimine demonstrated great promise in both in vitro and in vivo preclinical models of Cryptosporidium infection. Unfortunately, a phase 2a clinical trial in HIV-infected adults with cryptosporidiosis did not identify any clofazimine treatment effect on Cryptosporidium infection burden or clinical outcomes. To explore whether clofazimine's lack of efficacy in the phase 2a trial may have been due to subtherapeutic clofazimine concentrations, a pharmacokinetic/pharmacodynamic modeling approach was undertaken to determine the relationship between clofazimine in vivo concentrations and treatment effects in multiple preclinical infection models. Exposure-response relationships were characterized using E max and logistic models, which allowed predictions of efficacious clofazimine concentrations for the control and reduction of disease burden. After establishing exposure-response relationships for clofazimine treatment of Cryptosporidium infection in our preclinical model studies, it was unmistakable that the clofazimine levels observed in the phase 2a study participants were well below concentrations associated with anti- Cryptosporidium efficacy. Thus, despite a dosing regimen above the highest doses recommended for mycobacterial therapy, it is very likely the lack of treatment effect in the phase 2a trial was at least partially due to clofazimine concentrations below those required for efficacy against cryptosporidiosis. It is unlikely that clofazimine will provide a remedy for the large number of cryptosporidiosis patients currently without a viable treatment option unless alternative, safe clofazimine formulations with improved oral absorption are developed. (This study has been registered in ClinicalTrials.gov under identifier NCT03341767.).

Context: Sport specialization during adolescence may affect future injury risk. This association has been demonstrated in some professional sport athletes., Objective: To determine the association between adolescent sport specialization levels in high school and injuries sustained during collegiate club sports., Design: Cross-sectional study., Setting: Paper and online surveys., Patients or Other Participants: Collegiate club-sport athletes., Main Outcome Measures(s): An anonymous survey was administered from September 2019 to May 2020. The survey included sport specialization classification via a commonly used 3-point scale (low, moderate, high) for each high school year (9th-12th), high school sports participation, and collegiate club-sport injury history. The number of years (0-4) an individual was highly specialized in high school was calculated. Individuals who participated in the same sport in high school and college were compared with individuals who played a different sport in college than in high school. An injury related to sport club activities was classified as arising from a contact, noncontact, or overuse mechanism required and the individual to seek medical treatment or diagnosis. Injuries were classified into overuse and acute mechanisms for the upper extremity, lower extremity (LE), and head/neck., Results: Single-sport participation and the number of years highly specialized in high school sport were not associated with college club-sport injuries (P > .1). Individuals who played a different collegiate club sport than their high school sport were more likely to report an LE or head/neck acute injury compared with athletes who played the same collegiate and high school sport (LE = 20% versus 8%, χ2 = 7.4, P = .006; head/neck = 16% versus 3%, χ2 = 19.4, P < .001)., Conclusions: Adolescent sport specialization was not associated with reported injuries in collegiate club-sport athletes. Collegiate club-sport athletic trainers should be aware that incoming students exploring a new sport may be at risk for LE and head/neck acute injuries., (© by the National Athletic Trainers' Association, Inc.)

Climate change will affect numerous crops in the future; however, perennial crops, such as tea, are particularly vulnerable. Climate change will also strongly influence fungal pathogens. Here, we predict how future climatic conditions will impact tea and its associated pathogens. We collected data on the three most important fungal pathogens of tea ( Colletotrichum acutatum , Co. camelliae , and Exobasidium vexans ) and then modeled distributions of tea and these fungal pathogens using current and projected climates. The models show that baseline tea-growing areas will become unsuitable for Camellia sinensis var. sinensis (15 to 32% loss) and C. sinensis var. assamica (32 to 34% loss) by 2050. Although new areas will become more suitable for tea cultivation, existing and potentially new fungal pathogens will present challenges in these areas, and they are already under other land-use regimes. In addition, future climatic scenarios suitable range of fungal species and tea suitable cultivation (respectively in CSS and CSA) growing areas are Co. acutatum (44.30%; 31.05%), Co. camelliae (13.10%; 10.70%), and E. vexans (10.20%; 11.90%). Protecting global tea cultivation requires innovative approaches that consider fungal genomics as part and parcel of plant pathology., Competing Interests: Author SR was employed by N. Gene Solution of Natural Innovation, Kathmandu, Nepal. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tibpromma, Dong, Ranjitkar, Schaefer, Karunarathna, Hyde, Jayawardena, Manawasinghe, Bebber, Promputtha, Xu, Mortimer and Sheng.)

This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum). We discuss the potential uses of BKIs for the treatment of diseases caused by apicomplexan parasites in animals and humans, and the improvements that need to be made to further develop BKIs., (Copyright © 2020. Published by Elsevier B.V.)

The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum , which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals. IMPORTANCE Cryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvum in vitro Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite's interactions with exogenous fatty acids during the initial stages of infection., (Copyright © 2020 VanDussen et al.)

Objective: To conduct a survey of parents to determine their knowledge of sport volume recommendations and examine their perceptions toward sport specialization., Design: Cross-sectional survey., Setting: Youth sport athletic tournaments, competitions, and practices., Patients or Other Participants: Parents (n = 1000, 614 women, age: 44.5 ± 6.7 years) of youth athletes completed the survey. Parents had to have a child between 10 and 18 years of age who participated in organized sport in the previous 12 months., Interventions: The survey was anonymous and consisted of yes/no and Likert-scale questions and consisted of background of parent and child and perceptions and knowledge of safe sport recommendations. An expert panel validated the survey., Main Outcome Measures: Data were summarized by frequencies, proportions (%), and mean values and SDs, when appropriate. Chi-square analyses were used to determine if parent sex influenced distributions., Results: Over 80% of parents had no knowledge of sport volume recommendations regarding h/wk (84.5%), mo/yr (82.2%), or simultaneous participation in multiple leagues (89.9%). Twenty-four percent of parents considered it appropriate to participate in multiple leagues in the same sport, whereas 60.5% considered it appropriate to participate in multiple leagues of a different sport. Thirty-four percent of parents indicated that they were concerned about the risk of injury in youth sports. Although 55% of parents considered sport specialization a problem in youth sports, only 43.3% thought that year-round sport participation increased the chances of sustaining an overuse injury. Female parents were more likely to be concerned about injury and believe that year-round sport participation results in overuse injury compared with men., Conclusions: Recommendations associated with youth sport participation are not well known. However, parents are concerned about the risk of injury and consider sport specialization a problem.

Post, EG, Trigsted, SM, Schaefer, DA, Cadmus-Bertram, LA, Watson, AM, McGuine, TA, Brooks, MA, and Bell, DR. Knowledge, attitudes, and beliefs of youth sports coaches regarding sport volume recommendations and sport specialization. J Strength Cond Res 34(10): 2911-2919, 2020-Overuse injuries in youth athletes are becoming increasingly common, which may be a result of the prevalence of year-round specialized sport participation. Previous research has identified sport volume recommendations related to months per year, hours per week, and simultaneous participation in multiple sports leagues. Coaches are a primary influence on a youth athlete's decision to specialize in a single sport. Therefore, identifying coaches' baseline beliefs and perceptions is important for developing strategies to educate coaches about safe sport participation. A total of 253 youth sport coaches (207 males) completed an anonymous online questionnaire regarding knowledge of sport volume recommendations and attitudes and beliefs regarding sport specialization. Eligible participants were required to serve as a head or assistant coach of a youth sport team in the past 12 months whose members were between the ages of 12 and 18 years. Most coaches were unaware of recommendations regarding the maximum number of months per year (79.4%), hours per week in 1 sport (79.3%), or number of simultaneous leagues for an athlete to participate in to reduce injury (77.6%). Fewer than half (43.2%) of all coaches were "very" or "extremely" concerned about the risk of injury in youth sports. A majority (60.1%) believed that sport specialization was either "quite a bit" or "a great deal" of a problem. Two-thirds (67.2%) responded that year-round participation in a single sport was either "very" or "extremely" likely to increase an athlete's risk of injury. Although the responses to this survey were predominantly from coaches from 1 state, our results suggest that coaches are unaware of sport volume recommendations but are concerned about specialization. Future efforts are needed to communicate these recommendations to coaches to reduce the risk of overuse injury in youth sports.

Context: Young athletes are encouraged to participate in high-intensity sport programs. However, most research on the association between training volume (TV) and injury has been performed on adult or professional athletes., Objective: To evaluate the association between acute and chronic TV (hours/week) and reported injury (yes/no) and evaluate the relationship between acute : chronic TV and injury while controlling for sex, age, and prior injury in young athletes., Design: Cohort study., Setting: Online surveys., Patients or Other Participants: Middle school-aged adolescents., Main Outcome Measure(s): We conducted a baseline survey at the start of the 2017-2018 academic year. The baseline survey solicited information regarding demographics, injury history, and primary sport. Subsequent surveys were delivered electronically at the start of each week. Information obtained with the weekly survey included weekly TV and injuries sustained the previous week. Injuries were reported and classified (eg, acute or gradual onset) by the participants. Weekly TV was aggregated as rolling averages over the prior 2, 3, and 4 weeks. Acute:chronic TV was calculated for each participant for every week as the prior week TV divided by the TV during the prior 2 (1 : 2), 3 (1 : 3), and 4 (1 : 4) weeks of the study period., Results: A total of 244 recruits participated. Higher average TV over the prior 4 weeks (odds ratio [OR] = 0.97; 95% confidence interval [CI] = 0.93, 1.00; P = .05) was associated with fewer reported injuries. Additionally, higher average TV over the prior 2 (OR = 0.96; 95% CI = 0.93, 0.99; P = .04), 3 (OR = 0.95; 95% CI = 0.91, 0.99; P = .02), and 4 (OR = 0.95; 95% CI = 0.91, 0.99; P = .05) weeks was associated with fewer reported acute injuries the following week. Acute:chronic TV and any injury type were not related., Conclusions: Consistent, higher levels of physical activity may offer protection against acute injury in young athletes., (© by the National Athletic Trainers' Association, Inc.)

Objectives: The purpose of this study was to compare the association of sport specialization with previous overuse and acute injuries between male and female adolescent athletes., Design: Cross-sectional study., Methods: Questionnaires were completed by adolescent athletes from various sports at sport club summer events in the state of Wisconsin. Adolescent athletes (12-18 years old) who were active in organized sports in the previous year were recruited. The questionnaire contained demographics, sport participation, sport specialization classification, and previous injury history. Sport specialization classification was determined using common methods in sport specialization research. Previous injury was restricted to athletic injuries that occurred in the past year., Results: Two-thousand and eleven participants (age=13.7±1.6 years, females=989) completed the questionnaire. Highly specialized athletes were more likely to report both acute and overuse injuries compared to low specialization athletes. However, this relationship differed by sex, with only moderate and highly specialized females being more likely (Moderate: OR [95%CI]=1.74 [1.18-2.58], p=0.005; High: OR [95%CI]=1.69 [1.14-2.53], p=0.010) to report an overuse injury compared to low specialization females. Highly specialized female athletes were more likely to report an acute injury (High: OR [95%CI]=1.46 [1.06-2.02], p=0.022) compared to low specialization females. Highly specialized male athletes were not associated with overuse or acute injuries., Conclusions: Highly specialized athletes were more likely to report acute and overuse injuries. However, when this analysis was separated by sex, only highly specialized females were more likely to report a previous overuse or acute injury., (Copyright © 2020 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new compound after such limited screening strongly encourages further mining of invertebrate symbionts for new anti-parasitic therapeutics., Competing Interests: The authors have declared that no competing interests exist.

Bumped Kinase Inhibitors, targeting Calcium-dependent Protein Kinase 1 in apicomplexan parasites with a glycine gatekeeper, are promising new therapeutics for apicomplexan diseases. Here we will review advances, as well as challenges and lessons learned regarding efficacy, safety, and pharmacology that have shaped our selection of pre-clinical candidates., (Copyright © 2020. Published by Elsevier Ltd.)

Context: Sport specialization among youth athletes has been associated with increased risk of overuse injuries. Previous research demonstrates that children perceive specialization to be beneficial in making their high school team and receiving athletic college scholarships. Previous research demonstrates that parents play a significant role in their child's sport experience. However, it is unknown if parents and children answer questions related to specialization factors in a similar manner., Objective: To evaluate the beliefs of youth athletes and parents on factors related to sport specialization and evaluate the level of agreement between dyads on sports specialization., Design: Cross-sectional., Setting: Online and paper surveys., Patients or Other Participants: Aim 1: 1998 participants (993 children and 1005 parents). Aim 2: 77 paired parent-child dyads., Interventions: Self-administered survey., Main Outcome Measures: The responses were summarized via frequency and proportions (%). Chi-squares were calculated between parent and child responses. Kappa coefficients were calculated for dyads to determine level of agreement. Sport specialization was classified using a common 3-point scale., Results: The parents were more concerned about risk of injury in sports compared with children (P < .001, χ2 = 231.4; parent: extremely: 7.1%; child: extremely: 3.7%). However, children were more likely to believe that specialization was associated with their chances of obtaining an athletic college scholarship compared with parents (P < .001, χ2 = 201.6; parent: very/extremely likely: 13.7%; child: very/extremely likely: 15.8%). Dyad subanalysis indicated a moderate level of agreement for "quitting other sports to focus on one sport" (κ = .50) and a low level of agreement for "identifying a primary sport" (κ = .30) and "training >8 months per year in primary sport" (κ = .32)., Conclusions: Parents and youth athletes had differing beliefs on the factors related to sport specialization. Dyad analysis shows that parents and children answer sport specialization classification questions differently. Health care providers should be aware of these differences, and messaging should be individualized to the audience.

Benjamin, CL, Hosokawa, Y, Curtis, RM, Schaefer, DA, Bergin, RT, Abegg, MR, and Casa, DJ. Environmental conditions, preseason fitness levels, and game workload: Analysis of a female NCAA DI National Championship Soccer Season. J Strength Cond Res 34(4): 988-994, 2020-The purpose of this study was to determine the independent and combined moderating effect of aerobic fitness and environmental conditions on physical workloads during collegiate female soccer matches. Nineteen National Collegiate Athletic Association female soccer athletes were included in this study (mean ± SD: age, 20.6 ± 1.4 years; height, 169 ± 6.1 cm; body mass 64.7 ± 5.3 kg). Maximal oxygen consumption (V[Combining Dot Above]O2max) was estimated from the yo-yo intermittent recovery test before preseason training and wet-bulb globe temperature (WBGT) was recorded onsite for home matches and at the nearest weather station for away matches. Relative distance (TD), relative high-speed running distance (%HSD), and relative high metabolic load (%HML) performance were collected during each match using a global positioning system unit (Viper Pod; STATSports, Chicago, IL). Statistically significant differences were observed in TD between LOW WBGT and MOD WBGT (mean difference [MD] = 7.08 m·min; effect size [ES] = 0.54; p < 0.001), in %HSD between LOW WBGT and MOD WBGT (MD = 1.97%; ES = 0.64; p = 0.01) and between LOW WBGT and HIGH WBGT (MD = 2.71%; ES = 1.01; p < 0.001), and in %HML between LOW WBGT and MOD WBGT (MD = 1.24%; ES = 0.56; p < 0.001) and between LOW WBGT and HIGH WBGT (MD = 1.55%; ES = 0.78; p = 0.01). There was a significant interaction between WBGT and V[Combining Dot Above]O2max for %HSD (p = 0.03). These findings demonstrate that physical performance metrics were affected by increased WBGT. In addition, aerobic fitness seemed to moderate the effect of increasing WBGT on %HSD, meaning maximizing aerobic capacity is important for optimizing running performance in the heat. Coaches and sports medicine staff could alter training time and session length based on environmental conditions as well as potentially use aggressive cooling strategies to mitigate the imposed heat stress and decrements in physical performance.

Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a moderate-to-severe diarrheal disease now recognized as one of the leading causes of morbidity and mortality in livestock globally, and in humans living in resource-limited parts of the world, particularly those with AIDS or malnourished individuals. This recognition has fueled efforts for the discovery of effective therapeutics. While recent progress in drug discovery has been encouraging, there are presently no acceptably effective parasite-specific drugs for the disease. The urgent need for new drug discovery or drug repurposing has also increased the need for refined animal models of clinical disease for therapeutic efficacy evaluation. Here, we describe an acute model of cryptosporidiosis using newborn calves to evaluate well-defined clinical and parasitological parameter outcomes, including the effect on diarrhea severity and duration, oocyst numbers produced, and multiple measures of clinical health. The model is highly reproducible and provides unequivocal direct measures of treatment efficacy on diarrhea severity and parasite replication.

Background: Significant evidence has emerged that sport specialization is associated with an increased risk of overuse injury in youth athletes. Several recommendations exist to reduce the risk of overuse injury in youth sports, but the risk of overuse injuries may be dependent on specific movements required by a given sport., Hypotheses: Associations between specialized sport participation and overuse injury will exist in volleyball athletes but not soccer or basketball athletes. Female athletes will be more likely to report an overuse injury in the previous year, regardless of sport., Study Design: Cross-sectional study., Level of Evidence: Level 3., Methods: Youth athletes between the ages of 12 and 18 years were recruited in-person at club team tournaments, competitions, and events around the state of Wisconsin during the 2016-2017 school year. Participants were asked to complete an anonymous questionnaire that consisted of (1) participant demographics, (2) sport specialization status, (3) monthly and weekly sport volume, and (4) sport-related injury history in the previous year., Results: A total of 716 youth athletes completed the questionnaire (70.8% female; mean age, 14.21 ± 1.50 years; 43.2% basketball, 19.4% soccer, 37.4% volleyball; 41.8% highly specialized; 32.3% reported overuse injury in the previous year). Sex was associated with overuse injury among basketball athletes, with female basketball athletes nearly 4 times more likely to report an overuse injury compared with male basketball athletes (odds ratio, [OR], 3.7; 95% CI, 2.1-6.6; P < 0.001). High specialization (OR, 2.3; 95% CI, 1.1-4.9; P = 0.02) and participating in a single sport for more than 8 months per year (OR, 2.0; 95% CI, 1.1-3.5; P < 0.05) were associated with overuse injury only among volleyball athletes., Conclusion: Specialization and exceeding 8 months per year in a single sport was associated with overuse injury in volleyball, which is one of the most popular youth sports for female athletes. Specialization was not associated with overuse injury in basketball or soccer athletes. Female basketball athletes were nearly 4 times more likely to report a history of overuse injury compared with male basketball athletes. The sex of a youth athlete and the sport that he or she plays may influence the risk of overuse injury associated with sport specialization., Clinical Relevance: Youth athletes, parents, and clinicians should be aware that the potential risks of specialization might vary based on the athlete's sport and sex.

Context: Recent studies suggested that a large population of high school-aged athletes participate on club sport teams. Despite attempts to document emergency preparedness in high school athletics, the adherence to emergency and medical coverage standards among club sport teams is unknown., Objective: To determine if differences in emergency preparedness and training existed between coaches of high school teams and coaches of high school-aged club teams., Design: Cross-sectional survey., Setting: Online questionnaire., Patients or Other Participants: A total of 769 coaches (females = 266, 34.6%) completed an anonymous online questionnaire regarding their emergency preparedness and training., Main Outcome Measure(s): The questionnaire consisted of (1) demographics and team information, (2) emergency preparedness factors (automated external defibrillator [AED] availability, emergency action plan [EAP] awareness, medical coverage), and (3) emergency training requirements (cardiopulmonary resuscitation/AED, first aid)., Results: High school coaches were more likely than club sport coaches to be aware of the EAP for their practice venue (83.9% versus 54.4%, P < .001), but most coaches in both categories had not practiced their EAP in the past 12 months (70.0% versus 68.9%, P = .54). High school coaches were more likely to be made aware of the EAP during competitions (47.5% versus 37.1%, P = .02), but the majority of coaches in both categories indicated that they were never made aware of EAPs. High school coaches were more likely than club coaches to (1) have an AED available at practice (87.9% versus 58.8%, P < .001), (2) report that athletic trainers were responsible for medical care at practices (31.2% versus 8.8%, P < .001) and competitions (57.9% versus 31.2%, P < .001), and (3) be required to have cardiopulmonary resuscitation, AED, or first-aid training ( P < .001)., Conclusions: High school coaches displayed much greater levels of emergency preparedness and training than coaches of high school-aged club teams. Significant attention and effort may be needed to address the lack of emergency preparedness and training observed in club coaches.

Context: Previous researchers have identified sport specialization as being associated with various negative outcomes (eg, overuse injuries and adverse psychosocial outcomes). However, little is known regarding how the underlying attitudes, beliefs, and values of sport stakeholders may be shaping this trend., Objective: To examine the perceptions of coaches in the high school versus club sport setting and compare their attitudes and behaviors toward sport specialization., Design: Cross-sectional survey., Patients or Other Participants: A total of 769 coaches (497 high school coaches, 272 club sport coaches)., Main Outcome Measure(s): Participants completed a novel measure that surveyed their perceptions regarding various aspects of youth sport specialization. Additionally, each coach completed a questionnaire detailing his or her relevant demographic and sport background information., Results: High school coaches and club sport coaches differed in their perceptions of sport specialization ( t 767 = 1.41, P < .001); club coaches (2.43 ± 0.25) were more likely than high school coaches (2.31 ± 0.21) to rate specialization as a positive, adaptive practice. The multiple linear regression equations for both the high school and club coaches indicated that no educational, experiential, or demographic factors predicted coaches' perceptions of specialization ( P values > .05)., Conclusions: Club sport coaches were more likely to possess attitudes in favor of sport specialization. Additionally, coaches' background characteristics did not predict their perceptions of specialization, suggesting that the competitive context itself (high school versus club) may be the most salient influencer of these perceptions. Athletes and sports medicine practitioners should be aware of the heightened expectation of specialized participation and resulting increased injury risk in these contexts. Pediatric sport researchers and practitioners should continue to explore how these different group perceptions manifest in participation behaviors and may link to overall athlete health, wellbeing, and development.

Background: Club sport participation is increasingly common among high school athletes. Sport participation characteristics may vary widely between the high school and club sport settings. However, there have been no large-scale comparisons of sport participation volume between high school and club teams from similar sports., Purpose/hypothesis: The purpose of this study was to compare the sport participation characteristics of high school and high school-aged club teams. We hypothesized that club team athletes would participate in more months per year and hours per week and would take more overnight trips than high school athletes and that club team coaches would be less likely to track their athletes' sport volume than high school coaches., Study Design: Cross-sectional study., Methods: A total of 769 coaches (266 female; 34.6%) from 3 sports (basketball, volleyball, soccer) completed an anonymous online questionnaire regarding their team's sport volume and their knowledge, attitudes, and beliefs regarding sport specialization. Coaches were eligible to participate if they had served as the head or assistant coach of a high school sport team or high school-aged club sport team in the past 12 months., Results: Overall, 64.6% (n = 497) were coaches of a high school team, and 35.4% (n = 272) were coaches of a club team with high school-aged athletes. Club coaches' teams played more months out of the year and took more overnight trips for competitions than high school coaches' teams but participated in fewer hours per week of practices or competitions during their season. There were no differences between club and high school coaches in tracking their athletes' sport volume, with most coaches in both settings reporting that they do not track the amount of time that their athletes participate in other sports., Conclusion: Significant differences in sport participation volume exist between the teams of high school and club coaches., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.A.B. has received research funding from DJO Global and AnthroTronix and has received a consulting fee from the National Basketball Association–GE Healthcare. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objectives: To describe the socioeconomic status, measured by household income and educational attainment, of parents with children participating on youth club sport teams., Design: Cross-sectional survey., Setting: Local sport events., Participants: 949 parents (571 female) of youth athletes between 10 and 18 years old were recruited at club team events and practices to complete an anonymous questionnaire., Main Outcome Measures: SES variables included total household income (THI) and educational attainment. Sport specialization was classified as low, moderate, or high using a previously utilized 3-point specialization scale. Chi-square tests were used to compare frequencies SES categories with child specialization., Results: Parents reported spending a median of 1500 [500-3000] USD per year on their children's club sports activities. Most parents reported a THI greater than 100,000 USD per year and a bachelor's degree or higher level of education. Parents in the higher THI categories were more likely to have a child that is highly specialized in one sport., Conclusion: The current youth sports system in the United States, which emphasizes year-round participation on club teams, may be limiting the participation of families without the resources to participate in this system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Stem-cell-derived organoids recapitulate in vivo physiology of their original tissues, representing valuable systems to model medical disorders such as infectious diseases. Cryptosporidium, a protozoan parasite, is a leading cause of diarrhoea and a major cause of child mortality worldwide. Drug development requires detailed knowledge of the pathophysiology of Cryptosporidium, but experimental approaches have been hindered by the lack of an optimal in vitro culture system. Here, we show that Cryptosporidium can infect epithelial organoids derived from human small intestine and lung. The parasite propagates within the organoids and completes its complex life cycle. Temporal analysis of the Cryptosporidium transcriptome during organoid infection reveals dynamic regulation of transcripts related to its life cycle. Our study presents organoids as a physiologically relevant in vitro model system to study Cryptosporidium infection.

Background: There are a variety of proposed motivations for sport specialization, such as improving sport skills to an elite level, making all-star or travel teams, or receiving a scholarship or professional contract. However, there has not been a quantitative examination of the attitudes and beliefs that may be contributing to the trend of sport specialization and year-round sport participation., Purpose: The primary aim was to describe the attitudes and beliefs of youth club sport athletes regarding sport specialization and sport participation. A secondary objective was to investigate whether an association exists between the level of sport specialization and the belief in receiving a college scholarship., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A total of 974 youth athletes (578 female; mean age, 14.2 ± 1.6 years) completed an anonymous questionnaire that focused on attitudes and beliefs toward sport specialization and sport participation. Questions were developed utilizing the feedback of a panel of content area experts and the University of Wisconsin Survey Center. Data were summarized using frequencies, proportions (%), and means ± SDs., Results: Fewer than half of all athletes (45.8%) believed that specialization increased their chances of getting injured either "quite a bit" or "a great deal." However, 91% of athletes believed that specialization increased their chances of getting better at their sport either "quite a bit" or "a great deal." Similarly, the majority of athletes believed that specialization increased their chances of making their high school team (80.9%) or a college team (66.9%) either "quite a bit" or "a great deal." Overall, 15.7% of athletes believed that they were either "very" or "extremely" likely to receive a college scholarship based on athletic performance. Highly specialized athletes were nearly twice as likely to have a high belief in receiving a college scholarship compared with low-specialization athletes (20.2% vs 10.2%, respectively; χ 2 = 18.8; P = .001)., Conclusion: Most youth athletes in this study believe that specialization increases their sport performance and ability to make not only a college team but also their high school team. Highly specialized athletes were more likely to believe that they will receive a college scholarship., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by a grant that was cofunded by the American Medical Society for Sports Medicine and the American College of Sports Medicine. M.A.B. has received research funding from the National Collegiate Athletic Association, the Department of Defense, DJO Global, and AnthroTronix and has received consulting fees from the National Basketball Association–GE Healthcare to review scientific research proposals.

Background: Sport specialization has been associated with overuse injuries and is more common in larger high schools, which are often located in more urban/suburban settings. However, sport participation characteristics have not been compared between suburban and rural high schools., Purpose/hypothesis: The purpose of this study was to examine the differences in sport participation characteristics between athletes at suburban and rural high schools. It was hypothesized that suburban high school students would be more likely to be highly specialized, participate in more athletic competitions per year, and play in a league outside of school. We also hypothesized that suburban high school students would start playing their primary sport at a younger age, would have participated in their primary sport for longer, and would play more months per year and hours per week., Study Design: Cross-sectional study., Methods: High school athletes from 4 high schools (2 suburban and 2 rural) participated in this study (N = 354 [222 females]; mean age, 15.7 ± 1.2 years). Athletes were on a school-sponsored athletic team in 1 of 4 sports (volleyball, tennis, basketball, soccer). The suburban schools (study enrollment, n = 226) had total school enrollments of 2271 and 622 students, while the rural schools (study enrollment, n = 128) had total school enrollments of 443 and 297. Participants completed a questionnaire prior to the start of their high school sport season. The questionnaire consisted of demographic information, a sport specialization scale, and sport participation information. Primary sport competition volume in the previous 12 months was classified as high (>60 primary sport competitions), moderate (30-60), or low (<30). Sport specialization status was classified via a 3-point scale as low, moderate, or high., Results: As compared with athletes at rural schools, athletes at suburban schools started playing their primary sport at a younger age (suburban, 7.8 ± 2.9 years; rural, 9.7 ± 3.2 years; P < .001) and participated for more years (suburban, 7.9 ± 3.1 years; rural, 6.1 ± 3.3 years; P < .001), more months per year (suburban, 7.6 ± 3.6 months; rural, 5.6 ± 2.8 months; P < .001), and more hours per week (suburban, 15.2 ± 5.1 hours; rural, 12.9 ± 3.3 hours; P < .001). Athletes at suburban schools were more likely than rural athletes to be classified as highly specialized (χ 2 = 52.5, P < .001), participate in more competitions (χ 2 = 16.5, P < .001), play in a league outside of school (χ 2 = 18.4, P < .001), and train in their primary sport for >8 months per year (χ 2 = 27.8, P < .001) and >16 hours per week (χ 2 = 15.0, P < .001)., Conclusion: High school athletes at suburban schools are more likely to exhibit sport participation patterns that are associated with increased risk of overuse injury. These include being classified as highly specialized, playing their primary sport >8 months per year and >16 hours per week, engaging in a high competition volume, and participating in a sport league (eg, club) outside of school. Efforts aimed at safe sport participation should target these groups, as they seem more likely to violate safe sport recommendations., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported in part by a grant from the American Medical Society for Sports Medicine.