RESUMO
Researchers at the Walter Reed Army Institute of Research have taken a joint service approach to filling an identified diagnostic capability gap by leveraging a vector surveillance assay. Specifically, the Army took a field-stable real-time polymerase chain reaction assay, developed by the Air Force, for dengue virus surveillance in arthropod vectors and collaborated with Navy researchers for utility in human diagnostics. As current Department of Defense diagnostic PCR assays employ the Joint Biological Agent Identification and Diagnostic System, the dengue assay was tested for use on this platform. The low rates of false negative and false positive dengue samples in clinical matrices demonstrate excellent utility as a human diagnostic assay. Overall, converting an arboviral vector surveillance assay to human diagnostic assay and potentially vice versa is both cost effective and labor reducing. Codevelopment with harmonization of vector surveillance and diagnostics offers monetary and resource advantages to the Department of Defense and should be considered as a path forward in times when downsizing threatens assay development and pathogen discovery.
Assuntos
Aedes/virologia , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Insetos Vetores/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Animais , Estudos de Coortes , Humanos , Militares , Peru , Vigilância da População , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Sensibilidade e Especificidade , Estados UnidosRESUMO
BACKGROUND: Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia-reperfusion injury after aortic occlusion results from TLR-4-mediated microglial activation in mice. METHODS AND RESULTS: TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines. CONCLUSIONS: The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4-mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.
Assuntos
Microglia/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia do Cordão Espinal/metabolismo , Receptor 4 Toll-Like/fisiologia , Animais , Sobrevivência Celular/fisiologia , Células Cultivadas , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Traumatismo por Reperfusão/patologia , Isquemia do Cordão Espinal/patologia , Receptor 4 Toll-Like/deficiênciaRESUMO
Cardiorespiratory and transcutaneous oxygen monitors were used on 13 preterm neonates to examine physiologic changes during ductus arteriosus ligation. Transcutaneous oxygen decreased 30 seconds after left lung deflation; all infants required increases in inspired oxygen and ventilation to correct abnormal values after the left lung was compressed. Transcutaneous oxygen decreased 30 seconds after ductus arteriosus ligation (mean delta tcPO2 = -17 mm Hg +/- 11.4) but increased 150 seconds after left lung inflation (mean delta tcPO2 = 46.9 mm Hg +/- 28.8). Arterial blood pressure increased (mean delta systolic BP = 17.9 mm Hg +/- 9.5) and heart rate decreased 10 seconds after ductus arteriosus ligation. In five neonates, gradual closure of the ductus arteriosus over 40 to 75 seconds resulted in a more gradual increase in blood pressure. Intraventricular hemorrhage was confirmed in two patients after surgery. Ligation of the ductus arteriosus results in an abrupt increase in blood pressure, which may be related to the pathogenesis of intraventricular hemorrhage. We suggest that the ductus arteriosus be closed gradually to allow a more gradual increase in blood pressure.
Assuntos
Permeabilidade do Canal Arterial/cirurgia , Doenças do Prematuro/cirurgia , Pressão Sanguínea , Hemorragia Cerebral/etiologia , Frequência Cardíaca , Humanos , Recém-Nascido , Complicações Intraoperatórias , Ligadura/efeitos adversos , Pulmão/fisiologia , Métodos , Fatores de TempoRESUMO
The proportion of births to women of New Commonwealth origin in different Area Health Authorities (AHAs) varies widely. The influence of this varying proportion in contributing to differences in perinatal mortality rate (PNMR) between authorities is examined. Firstly, it is shown that the two main 'immigrant' groups have adverse PNMRs compared with Europeans, and that there is a positive correlation between the proportion of immigrant births in an Area and the PNMR. Secondly it is shown that immigrants have PNMRs (standardised for birth weight distribution) better than those of Europeans, and that there is a negative correlation between the proportion of immigrant births in an Area and the standardised PNMR of the whole Area. Thirdly, based on data from Birmingham a correction factor is developed and applied to the standardised PNMR to examine the effect of adjusting for racial mix. Factors other than birthweight contributint to variation between races in their PNMRs are discussed. It is concluded that the effect of race in contributing independently of birthweight to variation between Areas in respect of PNMRs is insufficient to invalidate inter-Area comparisons.
Assuntos
Etnicidade , Mortalidade Infantil , Ásia Ocidental/etnologia , Peso ao Nascer , Emigração e Imigração , Métodos Epidemiológicos , Europa (Continente)/etnologia , Feminino , Humanos , Recém-Nascido , Gravidez , Reino Unido , Índias Ocidentais/etnologiaRESUMO
The proportion of births to women of new commonwealth origin in different Area Health Authorities (AHAs) varies widely. The influence of this varying proportion in contributing to differences in perinatal mortality rate (PNMR) between authorities is examined. Firstly, it is shown that the two main immigrant groups have adverse PNMRs compared with Europeans, and that there is positive correlation between the proportion of immigrant births in an area and the PNMR. Secondly it is shown that immigrants have PNMRs (standardised for birth weight distribution) better than those of Europeans, and that there is negative correlation between the proportion of immigrant births in an area and the standardised PNMR of the whole area. Thirdly, based on data from Birmingham a correction factor is developed and applied to the standardised PNMR to examine the effect of adjusting for racial mix. Factors other than birthweight contributing to variation between races in their PNMRs are discussed. It is concluded that the effect of race in contributing independently of birthweight to variation between areas in respect of PNMRs is sufficient to validate inter area comparisons. (AU)