RESUMEN
Road user fatalities account for a leading cause of preventable death in Latin America with pedestrians and bicyclists at higher risk for more extensive injuries as compared to other road users. Despite these vulnerable road user (VRU) risks, encouraging individuals to walk and cycle is an important public health strategy for addressing the region's obesity epidemic through promoting physical activity via active transportation (AT). However, in order to promote AT as a viable source of physical activity, safety of the VRU must be considered. The purpose of this systematic review and metasummary is to describe the effectiveness of interventions that have been implemented in Latin America to improve pedestrian and bicyclist safety. A systematic search of public health, policy, and engineering databases was completed using terms generated through the PICO method. The PRISMA framework was used for article screening. Eight articles detailing nine interventions across four countries were included for final synthesis and organized according to the Three E's Model of Injury Prevention, including three education-based interventions, two engineering, three enforcements, and one utilizing all Three E's. VRU outcomes assessed ranged from attitudes and behaviors to fatal injuries, with only enforcement-based interventions reporting on the latter. No interventions reported on non-fatal injury outcomes. Interventions rooted in each arm of the Three E's demonstrated limited ability to improve VRU outcomes, with enforcement-based interventions providing the strongest body of evidence. Findings demonstrate the limited research on VRU safety in Latin America, and further efforts should be of urgent public health priority.
RESUMEN
OBJECTIVE: Investigate the requirement of Aggrecan (Acan) cleavage during aortic wall development in a murine model with ADAMTS (a disintegrin-like and metalloprotease domain with thrombospondin-type motifs) 5 deficiency and bicuspid aortic valves. APPROACH: Mice with altered extracellular matrix remodeling of proteoglycans will be examined for anomalies in ascending aortic wall development. Neo-epitope antibodies that recognize ADAMTS cleaved Acan fragments will be used to investigate the mechanistic requirement of Acan turnover, in aortic wall development. RESULTS: Adamts5-/-;Smad2+/- mice exhibited a high penetrance of aortic anomalies (n=17/17); Adamts5-/-;Smad2+/- mice with bicuspid aortic valves (7/17) showed a higher number of anomalies than Adamts5-/-;Smad2+/- mice with tricuspid aortic valves. Single mutant Adamts5-/- mice also displayed a high penetrance of aortic anomalies (n=19/19) compared with wild type (n=1/11). Aortic anomalies correlated with Acan accumulation that was apparent at the onset of elastogenesis in Adamts5-/- mice. Neo-epitope antibodies that recognize the initial amino acids in the Acan cleaved fragments neo-FREEE, neo-GLGS, and neo-SSELE were increased in the Adamts5-/- aortas compared with WT. Conversely, neo-TEGE, which recognizes highly digested Acan core fragments, was reduced in Adamts5-/- mice. However, mice containing a mutation in the TEGE373↓374ALGSV site, rendering it noncleavable, had low penetrance of aortic anomalies (n=2/4). Acan neo-DIPEN and neo-FFGVG fragments were observed in the aortic adventitia; Acan neo-FFGVG was increased abnormally in the medial layer and overlapped with smooth muscle cell loss in Adamts5-/- aortas. CONCLUSIONS: Disruption of ADAMTS5 Acan cleavage during development correlates with ascending aortic anomalies. These data indicate that the mechanism of ADAMTS5 Acan cleavage may be critical for normal aortic wall development.