ABSTRACT
Particulate matter (PM) exposure is a global health issue that impacts both urban and rural communities. Residential communities in the Southwestern United States have expressed concerns regarding the health impacts of fugitive PM from rural, legacy mine-sites. In addition, the recent literature suggests that exosomes may play a role in driving toxicological phenotypes following inhaled exposures. In this study, we assessed exosome-driven mechanisms and systemic health impacts following inhaled dust exposure, using a rodent model. Using an exosome inhibitor, GW4869 (10 µM), we inhibited exosome generation in the lungs of mice via oropharyngeal aspiration. We then exposed mice to previously characterized inhaled particulate matter (PM) from a legacy mine-site and subsequently assessed downstream behavioral, cellular, and molecular biomarkers in lung, serum, and brain tissue. Results indicated that CCL-2 was significantly upregulated in the lung tissue and downregulated in the brain (p < 0.05) following PM exposure. Additional experiments revealed cerebrovascular barrier integrity deficits and increased glial fibrillary acidic protein (GFAP) staining in the mine-PM exposure group, mechanistically dependent on exosome inhibition. An increased stress and anxiety response, based on the open-field test, was noted in the mine-PM exposure group, and subsequently mitigated with GW4869 intervention. Exosome lipidomics revealed 240 and eight significantly altered positive-ion lipids and negative-ion lipids, respectively, across the three treatment groups. Generally, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) lipids were significantly downregulated in the PM group, compared to FA. In conclusion, these data suggest that systemic, toxic impacts of inhaled PM may be mechanistically dependent on lung-derived, circulating exosomes, thereby driving a systemic, proinflammatory phenotype.
ABSTRACT
The United States has a rich history of mining including uranium (U)-mining, coal mining, and other metal mining. Cardiovascular diseases (CVD) are largely understudied in miners and recent literature suggests that when compared to non-U miners, U-miners are more likely to report CVD. However, the molecular basis for this phenomenon is currently unknown. In this pilot study, a New Mexico (NM)-based occupational cohort of current and former miners (n = 44) were recruited via a mobile screening clinic for miners. Serum- and endothelial-based endpoints were used to assess circulating inflammatory potential relevant to CVD. Non-U miners reported significantly fewer pack years of smoking than U-miners. Circulating biomarkers of interest revealed that U-miners had significantly greater serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (ICAM-1, ng/mL), soluble vascular cell adhesion molecule 1 (VCAM-1, ng/mL), and VCAM-1 mRNA expression, as determined by the serum cumulative inflammatory potential (SCIP) assay, an endothelial-based assay. Even after adjusting for various covariates, including age, multivariable analysis determined that U-miners had significantly upregulated VCAM-1 mRNA. In conclusion, VCAM-1 may be an important biomarker and possible contributor of CVD in U-miners. Further research to explore this mechanism may be warranted.
ABSTRACT
BACKGROUND: With a reported incidence of up to 10% compared to all spinal trauma, spinal injuries in children are less common than in adults. Children can have spine fractures with or without myelopathy, or spinal cord injuries without radiological abnormalities (SCIWORA). METHODS: We retrospectively reviewed the cases of children with spinal injuries treated at a level 1 pediatric trauma centre between 1990 and 2013. RESULTS: A total of 275 children were treated during the study period. The mean age at admission was 12 ± 4.5 years, and the male:female ratio was 1.4:1. Spinal injuries were more common in children of ages 12-16 years, with most injuries among ages 15-16 years. The top 3 mechanisms of spinal injury were motor vehicle-related trauma (53%), sports (28%) and falls (13%). Myelopathy occurred in 12% and SCIWORA occurred in 6%. The most common spine levels injured were L2-sacrum, followed by O-C2. Associated injuries, including head injuries (29%), and fractures/dislocations (27%) occurred in 55% of children. Overall mortality was 3%. Surgical intervention was required in 14%. CONCLUSION: The creation of a pediatric spinal injury database using this 23-year retrospective review helped identify important clinical concepts; we found that active adolescent boys had the highest risk of spine injury, that noncontiguous spine injuries occured at a rate higher than reported previously and that nonaccidental spine injuries in children are underreported. Our findings also emphasize the importance of maintaining a higher index of suspicion with trauma patients with multiple injuries and of conducting detailed clinical and radiographic examinations of the entire spine in children with a known spinal injury.
CONTEXTE: Les traumatismes médullaires sont moins fréquents chez l'enfant que chez l'adulte, avec une incidence d'au plus 10 % de tous les cas déclarés. Les enfants peuvent subir des fractures de la colonne vertébrale avec ou sans myélopathie, ou un traumatisme médullaire sans anomalie radiologique visible (SCIWORA). MÉTHODES: Nous avons effectué une analyse rétrospective des cas d'enfants atteints d'un traumatisme médullaire admis dans un centre de traumatologie spécialisé en pédiatrie de niveau 1 entre 1990 et 2013. RÉSULTATS: Au total, 275 enfants ont été traités durant la période de l'étude. L'âge moyen au moment de l'hospitalisation était de 12 ± 4,5 ans, et le ratio garçons:filles était de 1,4:1. Les adolescents de 12 à 16 ans formaient le groupe le plus représenté, et l'incidence de traumatisme la plus élevée a été observée chez les jeunes de 15 et 16 ans. Les 3 mécanismes lésionnels les plus fréquents étaient les accidents de la route (53 %), la pratique d'un sport (28 %) et les chutes (13 %). Le taux d'incidence de la myélopathie était de 12 %, et celui du SCIWORA, de 6 %. La section du rachis touchée le plus fréquemment s'étendait de L2 au sacrum, les vertèbres entre l'occiput et C2 arrivant au deuxième rang. Des lésions concomitantes, dont des blessures à la tête (29 %) et des fractures et luxations (27 %), ont été observées chez 55 % des enfants. Le taux global de mortalité était de 3 %. L'intervention chirurgicale a été nécessaire chez 14%. CONCLUSION: La création à partir de cette étude rétrospective d'une base de données sur les traumatismes médullaires chez l'enfant a mis en évidence quelques constatations cliniques dignes d'intérêt : les garçons adolescents actifs présentent le risque le plus élevé de traumatisme médullaire; les lésions médullaires non contiguës surviennent plus fréquemment que ce qui avait été rapporté précédemment; les traumatismes médullaires non accidentels chez l'enfant sont sous-déclarés. Nos conclusions viennent aussi souligner l'importance de maintenir un indice de suspicion élevé dans le cas de patients atteints de lésions multiples et d'effectuer un examen clinique et radiographique détaillé de la totalité de la colonne vertébrale des enfants ayant une lésion médullaire connue.
