Effects of Phosphodiesterase 4 Inhibition on Alveolarization and Hyperoxia Toxicity in Newborn Rats

International audienceBACKGROUND: Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. METHODOLOGY/FINDINGS: Rat pups were placed under hyperoxia (FiO2>95%) or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. CONCLUSIONS: Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization

The 2018 GaN power electronics roadmap

Gallium nitride (GaN) is a compound semiconductor that has tremendous potential to facilitate economic growth in a semiconductor industry that is silicon-based and currently faced with diminishing returns of performance versus cost of investment. At a material level, its high electric field strength and electron mobility have already shown tremendous potential for high frequency communications and photonic applications. Advances in growth on commercially viable large area substrates are now at the point where power conversion applications of GaN are at the cusp of commercialisation. The future for building on the work described here in ways driven by specific challenges emerging from entirely new markets and applications is very exciting. This collection of GaN technology developments is therefore not itself a road map but a valuable collection of global state-of-the-art GaN research that will inform the next phase of the technology as market driven requirements evolve. First generation production devices are igniting large new markets and applications that can only be achieved using the advantages of higher speed, low specific resistivity and low saturation switching transistors. Major investments are being made by industrial companies in a wide variety of markets exploring the use of the technology in new circuit topologies, packaging solutions and system architectures that are required to achieve and optimise the system advantages offered by GaN transistors. It is this momentum that will drive priorities for the next stages of device research gathered here

Radiochemical Applications in Industry – A Journey through Time with RC Tritec

Over the course of time, radioactive applications have changed from miracle cures to a material that is treated with caution in public perception. As a Swiss company, which has always been working with radioactive materials, RC Tritec is an interesting example how the applications in private industry have changed over the years: The company was originally a Ra-226 activated luminous paint manufacturer which managed to become a leader in the field of tritium labelling, the construction of manifolds for the handling of ionizing gases, source production and neutron imaging

Enablers and Barriers in Implementing Integrated Care.

Abstract-The integration of medical and social care aims to address the fragmentation in patient services observed in many health care systems. Increasing rates of chronic disease and multimorbidity have drawn attention to the often significant reforms necessary to address these problems. In this article we discuss how integration may be achieved. To date there is no single best practice model or well-defined guidelines for integration. We suggest that three groups of patients with complex health needs would experience the greatest benefit: multimorbid patients with two or more chronic diseases, patients with moderate or severe mental health conditions, and the elderly. Integration has been demonstrated to achieve improvements in the coordination, quality, efficiency, and cost control of health care. Considering these benefits, a broad effort should be made to implement integrated care

Unemployment, public–sector health care expenditure and HIV mortality: An analysis of 74 countries, 1981–2009

Background: The global economic downturn has been associated with increased unemployment and reduced public–sector expenditure on health care (PSEH). We determined the association between unemployment, PSEH and HIV mortality. Methods: Data were obtained from the World Bank and the World Health Organisation (1981–2009). Multivariate regression analysis was implemented, controlling for country–specific demographics and infrastructure. Time–lag analyses and robustness–checks were performed. Findings: Data were available for 74 countries (unemployment analysis) and 75 countries (PSEH analysis), equating to 2.19 billion and 2.22 billion people, respectively, as of 2009. A 1% increase in unemployment was associated with a significant increase in HIV mortality (men: 0.1861, 95% CI: 0.0977 to 0.2744, P = 0.0000, women: 0.0383, 95% CI: 0.0108 to 0.0657, P = 0.0064). A 1% increase in PSEH was associated with a significant decrease in HIV mortality (men: –0.5015, 95% CI: –0.7432 to –0.2598, P = 0.0001; women: –0.1562, 95% CI: –0.2404 to –0.0720, P = 0.0003). Time–lag analysis showed that significant changes in HIV mortality continued for up to 5 years following variations in both unemployment and PSEH. Interpretation Unemployment increases were associated with significant HIV mortality increases. PSEH increases were associated with reduced HIV mortality. The facilitation of access–to–care for the unemployed and policy interventions which aim to protect PSEH could contribute to improved HIV outcomes

Changes in government spending on healthcare and population mortality in the European union, 1995-2010:a cross-sectional ecological study

OBJECTIVE: Economic measures such as unemployment and gross domestic product are correlated with changes in health outcomes. We aimed to examine the effects of changes in government healthcare spending, an increasingly important measure given constrained government budgets in several European Union countries. DESIGN: Multivariate regression analysis was used to assess the effect of changes in healthcare spending as a proportion of total government expenditure, government healthcare spending as a proportion of gross domestic product and government healthcare spending measured in purchasing power parity per capita, on five mortality indicators. Additional variables were controlled for to ensure robustness of data. One to five year lag analyses were conducted. SETTING AND PARTICIPANTS: European Union countries 1995–2010. MAIN OUTCOME MEASURES: Neonatal mortality, postneonatal mortality, one to five years of age mortality, under five years of age mortality, adult male mortality, adult female mortality. RESULTS: A 1% decrease in government healthcare spending was associated with significant increase in all mortality metrics: neonatal mortality (coefficient −0.1217, p = 0.0001), postneonatal mortality (coefficient −0.0499, p = 0.0018), one to five years of age mortality (coefficient −0.0185, p = 0.0002), under five years of age mortality (coefficient −0.1897, p = 0.0003), adult male mortality (coefficient −2.5398, p = 0.0000) and adult female mortality (coefficient −1.4492, p = 0.0000). One per cent decrease in healthcare spending, measured as a proportion of gross domestic product and in purchasing power parity, was both associated with significant increases (p < 0.05) in all metrics. Five years after the 1% decrease in healthcare spending, significant increases (p < 0.05) continued to be observed in all mortality metrics. CONCLUSIONS: Decreased government healthcare spending is associated with increased population mortality in the short and long term. Policy interventions implemented in response to the financial crisis may be associated with worsening population health