118 research outputs found

    Acute Malnutrition and Under-5 Mortality, Northeastern Part of India.

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    We assessed the prevalence of childhood acute malnutrition and under-five mortality rate (U5MR) in Darbhanga district, India, using a two-stage 49-cluster household survey. A total of 1379 households comprising 8473 people were interviewed. During a 90-day recall period, U5MR was 0.5 [95% confidence interval (CI), 0.2-1.4] per 10 000 per day. The prevalence of global acute malnutrition among 1405 children aged 6-59 months was 15.4% (NCHS) and 19.4% (2006 WHO references). This survey suggests that in Darbhanga district, the population is in a borderline food crisis with few food resources. Appropriate strategies should be developed to improve the overall nutritional and health status of children

    NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity

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    <p>Abstract</p> <p>Background</p> <p>The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.</p> <p>Materials and methods</p> <p>We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual γH2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.</p> <p>Results</p> <p>Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of γH2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.</p> <p>Conclusions</p> <p>The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.</p

    Carbonyl sulfide : comparing a mechanistic representation of the vegetation uptake in a land surface model and the leaf relative uptake approach

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    Land surface modellers need measurable proxies to constrain the quantity of carbon dioxide (CO2) assimilated by continental plants through photosynthesis, known as gross primary production (GPP). Carbonyl sulfide (COS), which is taken up by leaves through their stomates and then hydrolysed by photosynthetic enzymes, is a candidate GPP proxy. A former study with the ORCHIDEE land surface model used a fixed ratio of COS uptake to CO2 uptake normalised to respective ambient concentrations for each vegetation type (leaf relative uptake, LRU) to compute vegetation COS fluxes from GPP. The LRU approach is known to have limited accuracy since the LRU ratio changes with variables such as photosynthetically active radiation (PAR): while CO2 uptake slows under low light, COS uptake is not light limited. However, the LRU approach has been popular for COS-GPP proxy studies because of its ease of application and apparent low contribution to uncertainty for regional-scale applications. In this study we refined the COS-GPP relationship and implemented in ORCHIDEE a mechanistic model that describes COS uptake by continental vegetation. We compared the simulated COS fluxes against measured hourly COS fluxes at two sites and studied the model behaviour and links with environmental drivers. We performed simulations at a global scale, and we estimated the global COS uptake by vegetation to be -756 Gg S yr(-1) , in the middle range of former studies (-490 to -1335 Gg S yr(-1)). Based on monthly mean fluxes simulated by the mechanistic approach in ORCHIDEE, we derived new LRU values for the different vegetation types, ranging between 0.92 and 1.72, close to recently published averages for observed values of 1.21 for C-4 and 1.68 for C-3 plants. We transported the COS using the monthly vegetation COS fluxes derived from both the mechanistic and the LRU approaches, and we evaluated the simulated COS concentrations at NOAA sites. Although the mechanistic approach was more appropriate when comparing to high-temporal-resolution COS flux measurements, both approaches gave similar results when transporting with monthly COS fluxes and evaluating COS concentrations at stations. In our study, uncertainties between these two approaches are of secondary importance compared to the uncertainties in the COS global budget, which are currently a limiting factor to the potential of COS concentrations to constrain GPP simulated by land surface models on the global scale.Peer reviewe

    Decentralized, primary-care delivered epilepsy services in Burera District, Rwanda: Service use, feasibility, and treatment

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    Background Integrating epilepsy care into primary care settings could reduce the global burden of illness attributable to epilepsy. Since 2012, the Rwandan Ministry of Health and the international nonprofit Partners In Health have collaboratively used a multi-faceted implementation program- MESH MH—to integrate and scale-up care for epilepsy and mental disorders within rural primary care settings in Burera district, Rwanda. We here describe demographics, service use and treatment patterns for patients with epilepsy seeking care at MESH-MH supported primary care health centers. Methods and findings This was a retrospective cohort study using routinely collected data from fifteen health centers in Burera district, from January 2015 to December 2016. 286 patients with epilepsy completed 3307 visits at MESH-MH participating health centers over a two year period (Jan 1st 2015 to Dec 31st 2016). Men were over twice as likely to be diagnosed with epilepsy than women (OR 2.38, CI [1.77–3.19]), and children under 10 were thirteen times as likely to be diagnosed with epilepsy as those 10 and older (OR 13.27, CI [7.18–24.51]). Carbamazepine monotherapy was prescribed most frequently (34% of patients). Conclusion Task-sharing of epilepsy care to primary care via implementation programs such as MESH-MH has the potential to reduce the global burden of illness attributable to epilepsy

    Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells

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    Introduction: We assessed expression of p85 and p110a PI3K subunits in non-small cell lung cancer (NSCLC) specimens and the association with mTOR expression, and studied effects of targeting the PI3K/AKT/mTOR pathway in NSCLC cell lines. Methods: Using Automated Quantitative Analysis we quantified expression of PI3K subunits in two cohorts of 190 and 168 NSCLC specimens and correlated it with mTOR expression. We studied effects of two PI3K inhibitors, LY294002 and NVP-BKM120, alone and in combination with rapamycin in 6 NSCLC cell lines. We assessed activity of a dual PI3K/mTOR inhibitor
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