0292: Endothelial protein tyrosine phosphatase 1B deficiency reduces both endothelial and cardiac dysfunction of in a mouse model of aging

IntroductionAging is associated with an endothelial dysfunction, characterized by a decrease of nitric oxide (NO) production, which is a risk factor of development of cardiovascular diseases. However, the direct link between endothelial dysfunction and aggravation of cardiac function in aging is not established. We reported previously a new potent therapeutic approach of cardiovascular disease, based on inhibition of protein tyrosine phosphatase 1B (PTP1B), which both increases NO production (via restored PI3K/Akt/eNOS signaling) and reduces cardiac dysfunction in both post-ischemic heart failure and aging, however the exact role of endothelial PTP1B in this setting is unknown. To evaluate the endothelial and cardiac consequences of endothelial PTP1B deficiency (endoPTP1B-/-) in a mouse model of aging.Material and methodsEndoPTP1B-/- mice were developed by crossing LOX-P PTP1B mice with mice expressing CRE under the control of the endothelial promoter Tie2, or wild-type (WT). The evolution of cardiac function was assessed by echocardiography at different time points and the vascular function was evaluated ex vivo at 24 months.ResultsCompared to young (3 month-old), WT mice aged (24 month-old) showed a markedly impaired flow-mediated dilatation of isolated mesenteric arteries (3 months: 40±4%; 24 months: 1±1%; p<0.001), which was improved in endoPTP1B-/- mice (17±3%; p<0.001 vs. WT 24 months). This restored response in aged endoPTP1B-/- mice was abolished by a NO-synthase inhibitor, suggesting a restored NO production. In WT mice, aging decreased stroke volume (3 months: 0,070±0,002%; 24 months: 0,065±0,005%; p<0.001) and cardiac output (3 months: 37±1%; 24 months: 29±2%; p<0.001) and these parameters were improved in endoPTP1B-/- mice (24 months: 0.081±0,011% and 34±2%; respectively, p<0.05).ConclusionIn aged mice, endoPTP1B deficiency induced an improvement of endothelial function, and also tended to improved cardiac function. These results provide a direct demonstration of the beneficial effect of endothelial protection in aging

Parental education and inequalitties in child mortality: a global systematic review and meta-analysis

The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals. This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data

Women’s political empowerment and child health in the sustainable development era: A global empirical analysis (1990–2016)

Empowering women is presented as a key strategy to achieve several goals of the sustainable development (SDG) agenda, including child health. However, the literature on the subject shows mixed results and is limited regarding political empowerment. Responding to this gap, we explore whether women’s political empowerment is associated with positive health outcomes for children under 5 years of age. We use the V-Dem project’s ‘Women’s Political Empowerment Index’ (WPEI) in combination with selected SDG indicators of child health from the Institute for Health Metrics and Evaluation’s 2017 Global Burden of Disease, for 161 countries, between 1990 and 2016. We estimate fixed-effects regressions for the WPEI against child mortality, stunting and immunisation coverage, controlling for structural and socio-economic indicators from the SDGs and potential lagged effects. The WPEI is associated with improved nutrition and immunisation but its substantive effect is small. High-, low-income and least developed countries benefit more from the effect of women’s political empowerment on child mortality. The effect of women’s political empowerment on stunting is stronger in middle-income countries while its effect on immunisation is more relevant to low-income and least developed countries. Our study demonstrates the complexity of the relations between women’s political empowerment and child health

Women’s political empowerment and child health in the sustainable development era: A global empirical analysis (1990–2016)

Empowering women is presented as a key strategy to achieve several goals of the sustainable development (SDG) agenda, including child health. However, the literature on the subject shows mixed results and is limited regarding political empowerment. Responding to this gap, we explore whether women’s political empowerment is associated with positive health outcomes for children under 5 years of age. We use the V-Dem project’s ‘Women’s Political Empowerment Index’ (WPEI) in combination with selected SDG indicators of child health from the Institute for Health Metrics and Evaluation’s 2017 Global Burden of Disease, for 161 countries, between 1990 and 2016. We estimate fixed-effects regressions for the WPEI against child mortality, stunting and immunisation coverage, controlling for structural and socio-economic indicators from the SDGs and potential lagged effects. The WPEI is associated with improved nutrition and immunisation but its substantive effect is small. High-, low-income and least developed countries benefit more from the effect of women’s political empowerment on child mortality. The effect of women’s political empowerment on stunting is stronger in middle-income countries while its effect on immunisation is more relevant to low-income and least developed countries. Our study demonstrates the complexity of the relations between women’s political empowerment and child health

Role of protein tyrosine phosphatase 1B in cardiovascular diseases

International audienceProtein Tyrosine Phosphatase 1B (PTP1B) is mostly involved in negative regulation of signaling mediated by Ty-rosine Kinase Receptors, especially the insulin and leptin receptors. This enzyme thus plays a major role in the development of diseases associated with insulin resistance, such as obesity and diabetes. PTP1B inhibition is currently considered as an attractive treatment of insulin resistance and associated metabolic disorders. In parallel, emerging evidence also suggests that PTP1B is widely expressed in cardiovascular tissues, notably in the heart and the endothelium, and that it could also be a potential treatment of several cardiovascular diseases. PTP1B is especially present in endothelial cells, and appears to contribute to endothelial dysfunction. Indeed, preclinical evidence shows that pharmacological inhibition of gene deletion of PTP1B reduces endothelial dysfunction in various cardiovascular diseases associated or not with insulin resistance. In parallel, because PTP1B also negatively modulates VEGF signaling, inhibition of this enzyme also tends to favor cardiac angiogenesis. Importantly, blocking PTP1B also results in beneficial effects on cardiac dysfunction and remodeling not only in metabolic diseases but also in the context of heart failure, thus this enzyme represents an attractive new target for the treatment of this disease. This beneficial effect in heart failure may to a large extent result from the endothelial protective and/or proangiogenic effects of PTP1B blockade. Finally, PTP1B inhibition also reduces cardiac dysfunc-tion, but also systemic inflammation and mortality in experimental models of septic shock, and thus may also constitute a new treatment of this disease. Altogether, accumulating preclinical evidence suggests that PTP1B represents an interesting molecular target to treat both cardiovascular and metabolic diseases, which often share the same risk factors. This concept now deserves to be tested in clinical studies that should soon be possible with the current development of selective PTP1B inhibitors

Broadband Antenna Radiation Pattern Measurement From Backscattering Coefficient in a Reverberation Chamber

International audienceThis paper deals with the contactless measurement of the radiation pattern of a log-periodic antenna within a reverberation chamber (RC). This method relies on backscattering measurement, i.e., avoiding to connect the antenna under test (AUT) to any analyzer, for two distinct AUT load conditions. The post-processing is based on a sinusoidal regression applied on the difference between the reflection coefficients measured for the two load conditions. A critical parameter to estimate is the frequency of the sinusoidal regression that depends here on the distance between the measurement antenna and the AUT. It is shown in this paper that the variation of the antenna phase center as a function of frequency has to be taken into account

Biased Estimation of Antenna Radiation Efficiency Within Reverberation Chambers Due to Unstirred Field: Role of Antenna Stirring

International audienceReverberation chambers (RCs) are now a reliable alternative to anechoic chambers to perform antenna radiation efficiency measurements. Most methods, including the two-antenna one used in this paper, are based on the evaluation of the stirred components of the scattering parameters. They are obtained by subtracting the average scattering parameters from the measured ones. This averaging is performed thanks to mechanical stirring, that is sometimes supplemented by additional stirring such as antenna stirring (which includes platform stirring and source stirring). In this paper, we present an extensive study on the role of antenna stirring in the retrieved radiation efficiency. Four measurement campaigns were successively performed: without antenna stirring, with platform stirring only, with source stirring only, and with a combined stirring of both antennas. Performing only source stirring or platform stirring leads to a biased estimation of the radiation efficiency. Therefore, we showed that the stirring of both antennas is mandatory in order to obtain an unbiased estimation of the radiation efficiency

Contactless Antenna Gain Pattern Estimation From Backscattering Coefficient Measurement Performed Within Reverberation Chambers

International audienceThis paper presents the antenna gain pattern estimation from backscattering coefficient measurement performed within a reverberation chamber (RC). The antenna backscattering coefficient is measured for two load conditions, namely an open circuit and a 50 Ω load, enabling to distinguish the radiation and structural modes from the total backscattered field. This approach is applied to the measurement of the gain pattern of a Vivaldi antenna at 6.5 GHz and compared to a conventional transmission-type measurement within an anechoic chamber. The main lobe of the radiation pattern is in good agreement between both measurements. The difference between maximal gains, retrieved after a reference measurement using a metallic plate, is equal to 0.04 dB. A second validation is performed using a log-periodic antenna at 3.5 GHz, showing less than 0.76 dB difference over the measured angular range. To the author's knowledge, this is the first time that a contactless gain pattern measurement is performed and validated within an RC

Mesure de l'efficacité de rayonnement d'antennes en chambre réverbérante : impact de l'estimation de l'efficacité de l'antenne de référence

International audienceLa caractérisation d'antenne en chambre réverbérante (CR) représente une nouvelle orientation dans le domaine des mesures d'antenne. Cet article compare deux méthodes de caractérisation d'antenne en CR. Ces méthodes sont appliquées dans le but de déterminer l'efficacité de rayonnement d'une antenne patch et d'une antenne log-périodique. Les résultats obtenus sont comparés et présentent une bonne cohérence. La précision des différentes méthodes appliquées est étudiée et une solution est proposée dans le but d'améliorer la précision de la méthode fondée sur l'utilisation d'une antenne de référence