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1.
PLoS One ; 12(9): e0184039, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28880936

RESUMO

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1ß and tumor necrosis factor (TNF)-α. MiR-503 expression was decreased in COPD lung fibroblasts. The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α. In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control. Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release. As expected, COPD fibroblasts proliferated more slowly than control fibroblasts. MiR-503 did not affect proliferation of either control or COPD lung fibroblasts. MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3' untranslated region of VEGF mRNA. Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2. Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF. In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD. Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD.


Assuntos
Fibroblastos/metabolismo , Regulação da Expressão Gênica , Pulmão/patologia , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Regiões 3' não Traduzidas/genética , Adulto , Sequência de Bases , Estudos de Casos e Controles , Células Cultivadas , Doença Crônica , Dinoprostona/metabolismo , Matriz Extracelular/metabolismo , Feminino , Fibronectinas/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
2.
Prehosp Disaster Med ; 32(2): 224-230, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28134064

RESUMO

Rural communities face barriers to disaster preparedness and considerable risk of disasters. Emergency preparedness among rural communities has improved with funding from federal programs and implementation of a National Incident Management System. The objective of this project was to design and implement disaster exercises to test decision making by rural response partners to improve regional planning, collaboration, and readiness. Six functional exercises were developed and conducted among three rural Nebraska (USA) regions by the Center for Preparedness Education (CPE) at the University of Nebraska Medical Center (Omaha, Nebraska USA). A total of 83 command centers participated. Six functional exercises were designed to test regional response and command-level decision making, and each 3-hour exercise was followed by a 3-hour regional after action conference. Participant feedback, single agency debriefing feedback, and regional After Action Reports were analyzed. Functional exercises were able to test command-level decision making and operations at multiple agencies simultaneously with limited funding. Observations included emergency management jurisdiction barriers to utilization of unified command and establishment of joint information centers, limited utilization of documentation necessary for reimbursement, and the need to develop coordinated public messaging. Functional exercises are a key tool for testing command-level decision making and response at a higher level than what is typically achieved in tabletop or short, full-scale exercises. Functional exercises enable evaluation of command staff, identification of areas for improvement, and advancing regional collaboration among diverse response partners. Obaid JM , Bailey G , Wheeler H , Meyers L , Medcalf SJ , Hansen KF , Sanger KK , Lowe JJ . Utilization of functional exercises to build regional emergency preparedness among rural health organizations in the US. Prehosp Disaster Med. 2017;32(2):224-230.


Assuntos
Planejamento em Desastres/organização & administração , Auxiliares de Emergência/educação , Regionalização da Saúde/organização & administração , Serviços de Saúde Rural/organização & administração , Treinamento por Simulação , Humanos , Nebraska , Desenvolvimento de Programas , Estados Unidos
3.
Prehosp Disaster Med ; 31(6): 658-662, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27640879

RESUMO

This report outlines a 3-year health care coalition effort to advance and test community capacity for a large-scale hospital evacuation. The multi-year effort utilized a variety workshops, seminars, webinars, tabletops, functional exercises, and culminated with a full-scale exercise testing hospital evacuation. While most hospital evacuation exercises focus on internal movement of patients, this exercise process tested command-level decision making and it tested external partners such as transportation agencies, law enforcement, receiving hospitals, and local emergency management. This process delivered key coalition-building activities and offered a variety of training and exercise opportunities to assist a number of organizations, all at different stages of hospital evacuation planning. The 2012 Hospital Preparedness Program outlined the incorporation of health care coalition activities to transform individual organization preparedness to community-level readiness. This report outlines a health care coalition effort to deliver training and exercises to advance community capacity for a large-scale hospital evacuation. Lowe JJ , Hansen KF , Sanger KK , Obaid JM . A 3-year health care coalition experience in advancing hospital evacuation preparedness. Prehosp Disaster Med. 2016;31(6):658-662.


Assuntos
Comportamento Cooperativo , Planejamento em Desastres/organização & administração , Hospitais , Trabalho de Resgate/normas , Coalizão em Cuidados de Saúde , Humanos , Avaliação de Programas e Projetos de Saúde
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