Understanding the Cheerleader as an Orthopaedic Patient: An Evidence-Based Review of the Literature.

Cheerleading is a highly popular youth sport in the United States and has been increasingly recognized in recent years for its athleticism and competitive nature. The sport has changed dramatically since its inception. When the sport of cheerleading was first developed, its primary purpose was to entertain crowds and support other athletes. Today, cheerleaders are competitive athletes themselves. Cheerleaders, most of whom are in the pediatric age group, and their parents commonly approach orthopaedic surgeons and sports medicine physicians with questions regarding the risks associated with participation in the sport. Appropriate clinical guidance is especially important for athletes returning to the sport after an injury. However, unlike other popular sports (eg, football, basketball, and volleyball), the intricacies of cheerleading are not well-known to those outside the sport, including many health care providers. Previous studies have reported on the epidemiological patterns of injuries associated with cheerleading and how such aesthetic sports affect the body, finding that fractures and concussions are prevalent and that catastrophic injuries are more common than in most other sports. Here, we provide an evidence-based discussion of 10 pertinent topics regarding cheerleading and its risks to the musculoskeletal system. The purpose of this review is to provide a comprehensive resource for orthopaedic surgeons and sports medicine physicians who care for these athletes.

Molecular target sequence similarity as a basis for species extrapolation to assess the ecological risk of chemicals with known modes of action.

It is not feasible to conduct toxicity tests with all species that may be impacted by chemical exposures. Therefore, cross-species extrapolation is fundamental to environmental risk assessment. Recognition of the impracticality of generating empirical, whole organism, toxicity data for the extensive universe of chemicals in commerce has been an impetus driving the field of predictive toxicology. We describe a strategy that leverages expanding databases of molecular sequence information together with identification of specific molecular chemical targets whose perturbation can lead to adverse outcomes to support predictive species extrapolation. This approach can be used to predict which species may be more (or less) susceptible to effects following exposure to chemicals with known modes of action (e.g., pharmaceuticals, pesticides). Primary amino acid sequence alignments are combined with more detailed analyses of conserved functional domains to derive the predictions. This methodology employs bioinformatic approaches to automate, collate, and calculate quantitative metrics associated with cross-species sequence similarity of key molecular initiating events (MIEs). Case examples focused on the actions of (a) 17α-ethinyl estradiol on the human (Homo sapiens) estrogen receptor; (b) permethrin on the mosquito (Aedes aegypti) voltage-gated para-like sodium channel; and (c) 17ß-trenbolone on the bovine (Bos taurus) androgen receptor are presented to demonstrate the potential predictive utility of this species extrapolation strategy. The examples compare empirical toxicity data to cross-species predictions of intrinsic susceptibility based on analyses of sequence similarity relevant to the MIEs of defined adverse outcome pathways. Through further refinement, and definition of appropriate domains of applicability, we envision practical and routine utility for the molecular target similarity-based predictive method in chemical risk assessment, particularly where testing resources are limited.

Cross-species sensitivity to a novel androgen receptor agonist of potential environmental concern, spironolactone.

Spironolactone is a pharmaceutical that in humans is used to treat conditions like hirsutism, various dermatologic afflictions, and female-pattern hair loss through antagonism of the androgen receptor. Although not routinely monitored in the environment, spironolactone has been detected downstream of a pharmaceutical manufacturer, indicating a potential for exposure of aquatic species. Furthermore, spironolactone has been reported to cause masculinization of female western mosquitofish, a response indicative of androgen receptor activation. Predictive methods to identify homologous proteins to the human and western mosquitofish androgen receptor suggest that vertebrates would be more susceptible to adverse effects mediated by chemicals like spironolactone that target the androgen receptor compared with invertebrate species that lack a relevant homolog. In addition, an adverse outcome pathway previously developed for activation of the androgen receptor suggests that androgen mimics can lead to reproductive toxicity in fish. To assess this, 21-d reproduction studies were conducted with 2 fish species, fathead minnow and Japanese medaka, and the invertebrate Daphnia magna. Spironolactone significantly reduced the fecundity of medaka and fathead minnows at 50 µg/L, whereas daphnia reproduction was not affected by concentrations as large as 500 µg/L. Phenotypic masculinization of females of both fish species was observed at 5 µg/L as evidenced by formation of tubercles in fathead minnows and papillary processes in Japanese medaka. Effects in fish occurred at concentrations below those reported in the environment. These results demonstrate how a priori knowledge of an adverse outcome pathway and the conservation of a key molecular target across vertebrates can be utilized to identify potential chemicals of concern in terms of monitoring and highlight potentially sensitive species and endpoints for testing.