Suchergebnisse

Access to the right to the highest attainable level of health is a constitutional right that obliges governments and other players to take step to increase all individuals' chances of obtaining good health. At the least, health and education are two crucial requirements for this as well. Iran's vision 2025 is going to lead the country to a developed state with the highest rank of economic, scientific and technological status in the region. Enjoying health, welfare, food security, social security, equal opportunities, etc, are also considered as part of characteristics of Iranian society in 2025. Although health system of Iran has many achievements in providing health services specially for the poor following the Islamic Revolution of 1979, but the evidences gathered to develop the 5th 5-years economical, social and cultural plan (5th5YDP:2011–2015), listed a variety of main challenges in stewardship, financing, resources generation and service provision functions of the existing health system. Thus, to overcome the main challenges, about 11% of general policies of 5th5YDP are directly address health related issues with emphasizing on healthy human and comprehensive health approach with considering: Integration of policy making, planning, evaluation, supervision and public financing; Developing both quantity and quality of health insurance system and reducing out-of-pocket expenditures for health services to 30% by the end of the 5th plan. The strategies of 5th5YDP adopted by the parliament as an Act will change the health system fundamentally through tuning the main drivers; so, its implementation needs brave leaders, capable managers, motivated technical staff and social mobilization.

3'-Phosphoinositide-dependent-Kinase-1(PDK1) is a master regulator whereby its PI3- kinase-dependent dysregulation in human pathologies is well documented. Understanding the direct role for Ptdlns(3,4,5)P-3 and other anionic phospholipids in the regulation of PDK1 conformational dynamics and its downstream activation remains incomplete. Using advanced quantitative-time-resolved imaging (Fluorescence Lifetime Imaging and Fluorescence Correlation Spectroscopy) and molecular modelling, we show an interplay of antagonistic binding effects of Ptdlns(3,4,5)P-3 and other anionic phospholipids, regulating activated PDK1 homodimers. We demonstrate that phosphatidylserine maintains PDK1 in an inactive conformation. The dysregulation of the PI3K pathway affects the spatio-temporal and conformational dynamics of PDK1 and the activation of its downstream substrates. We have established a new anionic-phospholipid-dependent model for PDK1 regulation, depicting the conformational dynamics of multiple homodimer states. We show that the dysregulation of the PI3K pathway perturbs equilibrium between the PDK1 homodimer conformations. Our findings provide a role for the PtdSer binding site and its previously unrewarding role in PDK1 downregulation, suggesting a possible therapeutic strategy where the constitutively active dimer conformer of PDK1 may be rendered inactive by small molecules that drive it to its PtdSer-bound conformer. ; Supported by the Spanish Ministry of Economy grant to B.L. [BFU2015- 65625-P] & Ministerio de Economía y Competitividad in Spain grant to J.R.-I., (MINECO FIS2009-07966); Royal Society grants to J.R.-I. and V.C. (IE120953). Basque Government PhD studentship to G.d.H.; Cancer Research UK Core Funding grants to B.L.; We also acknowledge the support of the Ikerbasque Foundation of Science to BL; Centre National de la Recherche Sciéntifique (CNRS) and Ministere de l'Education Nationale et de l'Enseignement Supérieur et de la Recherche (MENSR) grants to J.D.

Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries. © 2019 Elsevier Ltd