Injuries outside of horseracing: is it time to focus on injury prevention of jockeys outside of races?

Objectives: Falls and injuries are frequent in professional horseracing. However, professional jockeys spend a large part of their week in horse-related activities outside of racing such as schooling, exercise riding, and yard-related activities. The injury risk related to these activities remains largely unknown internationally. This study aimed to identify the injury prevalence and injury profile of flat and jump jockeys during non-racing activities. Methods: In total 45.6% and 38.5% of all licensed Irish professional flat and jump jockeys completed a cross-sectional self-recall questionnaire examining injuries that occurred outside of racing during 2018. Injury proportion, repeat incidence proportion, and descriptive statistics were calculated. Results: Fifteen percent of professional jockeys sustained an injury outside of a race, half of those injured receiving at least another injury in 2018 and 66.52 injuries per 1,000 falls were noted. Injuries frequently occurred to the upper limb (36.67%), with fractures common (32.00%). Most injuries occurred due to a fall (60.00%) and 77.27% occurred in the gallops. Half of injuries resulted in the jockey missing racing, with 31.00 ± 47.18 (4-180) days lost on average. Twenty-three percent of jockeys attended hospital and 16.67% required surgery due to injury. Interestingly, just under a third did not report their injury to anyone. Conclusion: Injuries to professional jockeys, whilst not as frequent outside of racing, tend to be serious and can affect jockeys financially and impact their availability to ride. Prioritizing injury prevention strategies to maximize availability of jockeys to race is important. Education on the importance of reporting all injuries regardless of where they occur is important to ensure their management and rehabilitation.

Calcineurin inhibitor (CNI)-associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery.

The use of the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus remains a cornerstone in post-transplantation immunosuppression. Although these immunosuppressive agents have revolutionized the field of transplantation medicine, its increased skin cancer risk poses a major concern. A key contributor to this phenomenon is a reduced capacity to repair DNA damage caused by exposure to ultraviolet (UV) wavelengths of sunlight. CNIs decrease DNA repair by mechanisms that remain to be fully explored. Though CsA is known to decrease the abundance of key DNA repair enzymes, less is known about how tacrolimus yields this effect. CNIs hold the capacity to inhibit both of the main catalytic calcineurin isoforms (CnAα and CnAß). However, it is unknown which isoform regulates UV-induced DNA repair, which is the focus of this review. It is with hope that this insight spurs investigative efforts that conclusively addresses these gaps in knowledge. Additionally, this research also raises the possibility that newer CNIs can be developed that effectively blunt the immune response while mitigating the incidence of skin cancers with immunosuppression.

Use of Big Data to Estimate Prevalence of Defective DNA Repair Variants in the US Population.

Importance: Wide use of genomic sequencing to diagnose disease has raised concern about the extent of genotype-phenotype correlations. Objective: To correlate disease-associated allele frequencies with expected and reported prevalence of clinical disease. Design, Setting, and Participants: Xeroderma pigmentosum (XP), a recessive, cancer-prone, neurocutaneous disorder, was used as a model for this study. From January 1, 2017, to May 4, 2018, the Human Gene Mutation Database and a cohort of patients at the National Institutes of Health were searched and screened to identify reported mutations associated with XP. The clinical phenotype of these patients was confirmed from reports in the literature and National Institutes of Health medical records. The genetically predicted prevalence of disease based on frequency of known pathogenic mutations was compared with the prevalence of patients clinically diagnosed with phenotypic XP. Exome sequencing of more than 200 000 alleles from the Genome Aggregation Database, the National Cancer Institute Division of Cancer Epidemiology and Genetics database of healthy controls, and an Inova Hospital Study database was used to investigate the frequencies of these mutations in the general population. Main Outcomes and Measures: Listing of all reported mutations associated with XP, their frequencies in 3 large exome sequence databases, determination of the number of patients in the United States with XP using modeling equations, and comparison of the observed and reported numbers of patients with XP with specific mutations. Results: A total of 156 pathogenic missense and nonsense mutations associated with XP were identified in the National Institutes of Health cohort and the Human Gene Mutation Database. The Genome Aggregation Database provided frequency data for 65 of these mutations, with a total allele frequency of 1.13%. The XPF (ERCC4) mutation, p.P379S, had an allele frequency of 0.4%, and the XPC mutation, p.P334H, had an allele frequency of 0.3%. With the Hardy-Weinberg equation, it was determined that there should be more than 8000 patients who are homozygous for these mutations in the United States. In contrast, only 3 patients with XP were reported as having the XPF mutation, and 1 patient was reported as having the XPC mutation. Conclusions and Relevance: The findings from this study suggest that clinicians should approach large genomic databases with caution when trying to correlate the clinical implications of genetic variants with the prevalence of disease risk. Unsuspected mutations in known genes with a predisposition for skin cancer may be responsible for some of the high frequency of skin cancers in the general population.