Background Elucidating the molecular pathogenesis underlying East Texas bleeding disorder (ET) led to the discovery of alternatively spliced F5 transcripts harboring large deletions within exon 13. These alternatively spliced transcripts produce a shortened form of coagulation factor V (FV) in which a large portion of its B‐domain is deleted. These FV isoforms bind tissue factor pathway inhibitor alpha (TFPIα) with high affinity, prolonging its circulatory half‐life and enhancing its anticoagulant effects. While two missense pathogenic variants highlighted this alternative splicing event, similar internally deleted FV proteins are found in healthy controls. Objective We identified a novel heterozygous 832 base pair deletion within F5 exon 13, termed F5‐Atlanta (F5‐ATL), in a patient with severe bleeding. Our objective is to investigate the effect of this deletion on F5 and FV expression. Methods & Results Assessment of patient plasma revealed markedly elevated levels of total and free TFPI and a FV isoform similar in size to the FV‐short described in ET. Sequencing analyses of cDNA revealed the presence of a transcript alternatively spliced using the ET splice sites, thereby removing the F5‐ATL deletion. This alternative splicing pattern was recapitulated by heterologous expression in mammalian cells. Conclusions These findings support a mechanistic model consisting of cis‐acting regulatory sequences encoded within F5 exon 13 that control alternative splicing at the ET splice sites and thereby regulate circulating FV‐short and TFPIα levels.

Hoverboards were recently introduced to the US consumer market and experienced rapid popularity. Given the high frequency of musculoskeletal injury with other wheeled recreation devices, we sought to analyze hoverboard injuries in children. A retrospective review of patients with musculoskeletal injury related to hoverboard use was performed at a tertiary care children's hospital. From November 2015 to January 2016, 2.3% of all fractures were related to hoverboards. Common injury mechanisms were fall (79%) and finger entrapment between wheel and wheel-well (10%). The most frequently fractured sites included the distal radius (43%) and phalanx (17%). Common surgical procedures were nailbed repair and pinning for Seymour fracture and percutaneous pinning for distal radius fracture. There exists high risk for distal radius fractures from falls and phalanx fractures from finger entrapment between the wheel and wheel-well. Hoverboard safety can be improved with regular use of wrist guards and improved wheel-well design.

Purpose: Despite the growing evidence that ecological factors contribute to substance use, the relationship of ecological factors and illicit drugs such as marijuana use is not well understood, particularly among adolescents in Latin America. Guided by social disorganization and social stress theories, we prospectively examined the association of disaggregated neighborhood characteristics with marijuana use among adolescents in Santiago, Chile, and tested if these relationships varied by sex. Methods: Data for this study are from 725 community-dwelling adolescents participating in the Santiago Longitudinal Study, a study of substance using behaviors among urban adolescents in Santiago, Chile. Adolescents completed a two-hour interviewer administered questionnaire with questions about drug use and factors related to drug using behaviors. Results: As the neighborhood levels of drug availability at baseline increased, but not crime or noxious environment, adolescents had higher odds of occasions of marijuana use at follow up, approximately 2 years later (odds ratio [OR] = 1.39; 95% CI = 1.16–1.66), even after controlling for the study’s covariates. No interactions by sex were significant. Discussion: The findings suggest that “poverty”, “crime”, and “drug problems” may not be synonyms and thus can be understood discretely. As Latin American countries re-examine their drug policies, especially those concerning decriminalizing marijuana use, the findings suggest that attempts to reduce adolescent marijuana use in disadvantaged neighborhoods may do best if efforts are concentrated on specific features of the “substance abuse environment”.

No abstract