Lung development and repair of hyperoxic injury require closely regulated growth and regeneration of alveolar capillaries. Vascular endothelial growth factor (VEGF), a mitogen for endothelial cells, is expressed by alveolar epithelial cells. Alternative splicing of VEGF mRNA results in isoforms of varying mitogenicity and solubility. We examined changes in the proportions of the VEGF splice variant mRNAs in rabbit lung development and in control, oxygen-injured, and recovering newborn and adult rabbit lungs. The proportion of the 189-amino acid VEGF mRNA, which codes for an isoform that binds to the extracellular matrix, increased fivefold during development (from 8% of total VEGF message at 22 days gestation to 40% in 10-day newborn lungs; P < 0.001). During neonatal oxygen injury, its expression declined from 38 to 8% of VEGF message ( P < 0.002) and returned to the control value in recovery. A similar pattern was observed in adults. VEGF protein in lung lavage fluid increased slightly during hyperoxia, declined to barely detectable levels at the 50% lethal dose time point, and increased 10-fold (newborn) or up to 40-fold (adult) in recovering animals. We conclude that alternative splicing may have important roles in the regulation of VEGF activity in developing and injured lungs.
BackgroundThe recent increase in childhood obesity is expected to add significantly to the prevalence of chronic diseases. We used multivariate multilevel analysis to examine associations between parks/green space and childhood overweight/obesity across communities in Calgary, Canada, a city characterized by intensified urban sprawl and high car use.MethodsBody Mass Index was calculated from measured height and weight data obtained from 6,772 children (mean age = 4.95 years) attending public health clinics for pre-school vaccinations. Each child's home postal code was geocoded using ESRI ArcGIS 9.2. We examined four measures of spatial access to parks/green space (based on Geographic Information Systems): 1) the number of parks/green spaces per 10,000 residents, 2) the area of parks/green space as a proportion of the total area within a community, 3) average distance to a park/green space, and 4) the proportion of parks/green space service area as a proportion of the total area within a community. Analyses were adjusted for dissemination area median family income (as a proxy for an individual child's family income) community-level education, and community-level proportion of visible minorities.ResultsIn general, parks/green space at the community level was not associated with overweight/obesity in Calgary, with the exception of a marginally significant effect whereby a moderate number of parks/green spaces per 10,000 residents was associated with lower odds of overweight/obesity. This effect was non-significant in adjusted analyses.ConclusionOur null findings may reflect the popularity of car travel in Calgary, Canada and suggest that the role built environment characteristics play in explaining health outcomes may differ depending on the type of urban environment being studied.
Previously we have demonstrated that prolonged exposure to 100% ambient oxygen leads to a marked loss in functional lung volume and lung compliance, hypoxemia, and surfactant system abnormalities similar to acute respiratory distress syndrome (ARDS). However, 50% oxygen administration is believed to be safe in most clinical settings. In the present study, we have evaluated the effects of a 24-h exposure to 50% oxygen in rabbits immediately following experimental gastric acid aspiration. Mild hypoxemia, but no changes in mortality, lung volume, lung compliance, surfactant metabolism, or edema formation occurred after 24 h of normoxia postacid aspiration. Conversely, a relatively short (24-h) exposure to 50% oxygen after acid aspiration results in increased pulmonary edema, physical signs of respiratory distress, and mortality, as well as decreased arterial oxygenation, lung volume, lung compliance, and type II alveolar cell surfactant synthesis. These results suggest that acid aspiration alters the "set point" for oxygen toxicity, possibly by "priming" cells through activation of inflammatory pathways. This pathogenic mechanism may contribute to the progression of aspiration pneumonia to ARDS.
Readmission and postoperative complications are common after intestinal resection in CD and UC. Clinicians should closely monitor surgical patients who required emergent admission, undergo surgery with stoma formation, or develop in-hospital postoperative complications to anticipate need for readmission or interventions to prevent readmission.
Introduction: In ischaemic stroke care, fast reperfusion is essential for disability free survival. It is unknown if bypassing thrombolysis centres in favour of endovascular thrombectomy (mothership) outweighs transport to the nearest thrombolysis centre for alteplase and then transfer for endovascular thrombectomy (drip-and-ship). We use conditional probability modelling to determine the impact of treatment times on transport decision-making for acute ischaemic stroke.Materials and methods: Probability of good outcome was modelled using a previously published framework, data from the Irish National Stroke Register, and an endovascular thrombectomy registry at a tertiary referral centre in Ireland. Ireland was divided into 139 regions, transport times between each region and hospital were estimated using Google's Distance Matrix Application Program Interface. Results were mapped using ArcGIS 10.3. Results: Using current treatment times, drip-and-ship rarely predicts best outcomes. However, if door to needle times are reduced to 30 min, drip-and-ship becomes more favourable; even more so if turnaround time (time from thrombolysis to departure for the endovascular thrombectomy centre) is also reduced. Reducing door to groin puncture times predicts better outcomes with the mothership model. Discussion: This is the first case study modelling pre-hospital transport for ischaemic stroke utilising real treatment times in a defined geographic area. A moderate improvement in treatment times results in significant predicted changes to the optimisation of a national acute stroke patient transport strategy. Conclusions: Modelling patient transport for system-level planning is sensitive to treatment times at both thrombolysis and thrombectomy centres and has important implications for the future planning of thrombectomy services.
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