Polypill for prevention of cardiovascular disease in an Urban Iranian population with special focus on nonalcoholic steatohepatitis: A pragmatic randomized controlled trial within a cohort (PolyIran - Liver) – Study protocol

Background: Cardiovascular disease (CVD) is among the most common causes of mortality in all populations. Nonalcoholic steatohepatitis is a common finding in patients with CVD. Prevention of CVD in individual patients typically requires periodic clinical evaluation, as well as diagnosis and management of risk factors such as hypertension and hyperlipidemia. However, this is resource consuming and hard to implement, especially in developing countries. We designed a study to investigate the effects of a simpler strategy: a fixed-dose combination pill consisting of aspirin, valsartan, atorvastatin and hydrochlorthiazide (PolyPill) in an unselected group of persons aged over 50 years. Design: The PolyIran-Liver study was performed in Gonbad city as an open label pragmatic randomized controlled trial nested within the Golestan Cohort Study. We randomly selected 2,400 cohort study participants aged above 50 years, randomly assigned them to intervention or usual care and invited them to participate in an additional measurement study (if they met the eligibility criteria) to measure liver related outcomes. Those agreeing and randomized to the intervention arm were offered a daily single dose of PolyPill. We will follow participants for 5 years. The primary outcome is major cardiovascular events, secondary outcomes include all-cause mortality and liver related outcomes: liver stiffness and liver enzyme levels. Cardiovascular outcomes and mortality will be determined from the cohort study and liver-related outcomes in those consenting to follow up. Analysis will be by allocated group. Trial Status: Between October and December 2011, 1,320 intervention and 1,080 control participants were invited to participate in the additional measurement study. For all these participants, the major cardiovascular events will be determined using blind assessment of outcomes through the cohort study. In the intervention and control arms, 875 (66%) and 721 (67%) respectively, met the eligibility criteria and agreed to participate in the additional measurement study. Liver related outcomes will be measured in these participants. Of the 1,320 participants randomized to the intervention, 787 (60%) accepted the PolyPill. Conclusion: The PolyIran-liver urban study will provide us with important information on the effectiveness of PolyPill on major cardiovascular events, all-cause mortality and liver related outcomes. (ClinicalTrials.gov ID: NCT01245608). © 2015, Academy of Medical Sciences of I.R. Iran. All rights reserved

Effects of pin diameter and number of cycles on microstructure and tensile properties of friction stir fabricated AA1050-Al2O3 nanocomposite

Nanocomposites of Al-Al2O3 are fabricated by means of friction stir processing (FSP). Effects of pin diameter and number of FSP cycles on tensile properties of the nanocomposites are investigated and the variations are correlated to the evolution of microstructure and distribution of nanoparticles in addition to agglomeration of Al2O3 nanoparticles. Investigation of agglomeration has been considered as an indirect indication for efficiency of the process for distribution of nanoparticles. The ductility of the nanocomposite is found to improve due to grain refinement during FSP. However, the ductility is likely to degrade if Al2O3 particles agglomerate and form coarse particles. The composite fabricated using the 6-mm pin indicates the maximum ductility which is attributed to formation of fine grain structure and efficient distribution of nanoparticles in the composite. Although, the grain structure in the composite fabricated using 8-mm pin is well refined, this sample shows significantly lower ductility with respect to the other samples. This was attributed to formation of coarse agglomerated particles. The second pass of FSP is found to slightly improve ductility and strength in composites fabricated using 4- and 6-mm pins but enforce significant improvements in the one with 8-mm pin. This is indeed because the second pass results in significant change in the distribution of nanoparticles or agglomerated particles in the latter case and negligible in the former ones. Grain structure and nanoparticle distribution and agglomeration can all affect the fracture surface of the tensile specimens of the fabricated nanocomposite to be ductile or brittle

A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors

SummaryAim: Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels. Methods: This was a double-blind randomised placebo-controlled trial in residents of Kalaleh, Golestan, Iran. Following an 8-week placebo run-in period, 475 participants, aged 50 to 79 years, without cardiovascular disease, hypertension or hyperlipidaemia were randomised to fixed-dose combination therapy with aspirin 81 mg, enalapril 2.5 mg, atorvastatin 20 mg and hydrochlorothiazide 12.5 mg (polypill) or placebo for a period of 12 months. The primary outcomes were changes in LDL-cholesterol, systolic and diastolic blood pressure and adverse reactions. Analysis was by intention-to-treat basis. Results: At baseline, there were differences in systolic blood pressure (6 mmHg). Taking account of baseline differences, at 12 months, polypill was associated with statistically significant reductions in blood pressure (4.5/1.6 mmHg) and LDL-cholesterol (0.46 mmol/l). The study drug was well tolerated, but resulted in the modest reductions in blood pressure and lipid levels. Conclusion: The effects of the polypill on blood pressure and lipid levels were less than anticipated, raising questions about the reliability of the reported compliance. There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease. © 2010 Blackwell Publishing Ltd

Static and vibration analysis of functionally graded beams using refined shear deformation theory

Static and vibration analysis of functionally graded beams using refined shear deformation theory is presented. The developed theory, which does not require shear correction factor, accounts for shear deformation effect and coupling coming from the material anisotropy. Governing equations of motion are derived from the Hamilton's principle. The resulting coupling is referred to as triply coupled axial-flexural response. A two-noded Hermite-cubic element with five degree-of-freedom per node is developed to solve the problem. Numerical results are obtained for functionally graded beams with simply-supported, cantilever-free and clamped-clamped boundary conditions to investigate effects of the power-law exponent and modulus ratio on the displacements, natural frequencies and corresponding mode shapes

CD8+ T Cells as a Source of IFN-γ Production in Human Cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is usually a self-healing skin lesion caused by different species of Leishmania parasite. Resistance and susceptibility of mice to Leishmania major infection is associated with two types of CD4+ T lymphocytes development: Th1 type response with production of cytokine IFN-γ is associated with resistance, whereas Th2 type response with production of cytokines IL-4 and IL-5 is associated with susceptibility. A clear Th1/Th2 dichotomy similar to murine model is not defined in human leishmaniasis and we need as much information as possible to define marker(s) of protection. We purified CD4+/CD8+ T cells, stimulated them with Leishmania antigens and analysed gene and protein expression of Th1/Th2 cytokines in volunteers with a history of self-healing CL who are presumed to be protected against further Leishmania infection. We have seen significant upregulation of IFN-γ gene expression and high IFN-γ production in the Leishmania stimulated CD4+ T cells and CD8+ T cells. We concluded that both antigen-specific IFN-γ producing CD4+ Th1 cells and IFN-γ producing CD8+ T cells contribute to the long term protection in individuals with a history of CL. This proves the importance of CD8+ T cells as a source of IFN-γ in Th1-like immune responses

Addressing vulnerability, building resilience:community-based adaptation to vector-borne diseases in the context of global change

Abstract Background The threat of a rapidly changing planet – of coupled social, environmental and climatic change – pose new conceptual and practical challenges in responding to vector-borne diseases. These include non-linear and uncertain spatial-temporal change dynamics associated with climate, animals, land, water, food, settlement, conflict, ecology and human socio-cultural, economic and political-institutional systems. To date, research efforts have been dominated by disease modeling, which has provided limited practical advice to policymakers and practitioners in developing policies and programmes on the ground. Main body In this paper, we provide an alternative biosocial perspective grounded in social science insights, drawing upon concepts of vulnerability, resilience, participation and community-based adaptation. Our analysis was informed by a realist review (provided in the Additional file 2) focused on seven major climate-sensitive vector-borne diseases: malaria, schistosomiasis, dengue, leishmaniasis, sleeping sickness, chagas disease, and rift valley fever. Here, we situate our analysis of existing community-based interventions within the context of global change processes and the wider social science literature. We identify and discuss best practices and conceptual principles that should guide future community-based efforts to mitigate human vulnerability to vector-borne diseases. We argue that more focused attention and investments are needed in meaningful public participation, appropriate technologies, the strengthening of health systems, sustainable development, wider institutional changes and attention to the social determinants of health, including the drivers of co-infection. Conclusion In order to respond effectively to uncertain future scenarios for vector-borne disease in a changing world, more attention needs to be given to building resilient and equitable systems in the present

Epidemiological study on some environmental and management parameters affecting on WSD occurrence in Fenneropenaeus indicus and Penaeus vannamei

For the first time white spot disease (WSD) was reported in shrimp farms of khoozestan province, in southwest of IRAN in 2002. Then in 2005 the neighbor province, boushehr, was contaminated. In 2008 WSD outbreak reported in sistan-bloochestan province in southeast of Iran. In 2015 all of southern shrimp farms of country except Hormozgan, the middle southern province, which has remained free of WSD, are being contaminated. White Spot disease suspended shrimp culture in thousands hectares of shrimp farms. Considering that white spot disease has not been observed in Hormozgan province yet, the question is; to what extent environmental and management factors participated in preventing WSD outbreak or cause WSD outbreak. In this study (20102012), the effects of environmental factors and management, stressors that decrease immune system function of shrimp are discussed. In addition, the role of pathogen as the main factor of outbreak is discussed. The goal of this study is to define environmental parameters and management practices associates with outbreak of white spot disease in affected provinces and discover reasons of being Hormozgan province free of this disease. In this study the role of the local environmental factors and management practice stressors in susceptibility to WSD was determine. Both the effects of environmental factors in water of ponds including total ammonia, nitrogen, dissolved oxygen, pH, salinity, transparency, and temperature and management issues related to biosecurity are studied. There were overlaps on physical and chemical parameter values obtained in clear areas with contaminated areas .Results of the data analysis suggest that lack of association with WSD incidence was 7 times greater than WSD incidence despite of disease outbreak in sistan-bloochestan province, so other sources of white spot disease virus incidence was suspected in affected areas. Histopathological examinations and polymerase chain reaction (PCR) tests during project performance did not reveal white spot disease virus evidences in post larvae examined from khoozestan province stocked in farms but disease outbreak was happened in that farms , so we suspected to management practice include feed , pond preparation and carrier of disease. Recorded values of temperature and salinity in some months during inspection in Hormozgan province specified stressful condition that may lead to WSD outbreak, however the disease did not appear. Therefore the hypothesis that the water physical and chemical conditions are reasons to prevent disease outbreak in Hormozgan province is being rejected. The policy of Hormozgan’s fishery authorities, to replaced Fenneropenaeus indicus with specific pathogen free Litopenaeus vannamei, that is more resistant to some of diseases, before incidence of WSD in farms and to before being endemic in the Hormozgan province, made an advantage compare to affected southern provinces that introduced Litopenaeus vannamei after WSD prevalence to their farms. However it does not guarantee to maintain current trend of being Hormozgan province farms free of white spot disease. Therefore establishing the principals of biosecurity are strongly emphasized. Strategies taken by the proficient authorities in preparation of SPF shrimp broodstock can be the most important factor in preventing WSD. Regarding biosecurity principals purchased feed must be free of shrimp head powder. Construction the new shrimp farms should be as far as it could be away from contaminated areas

Electrode kinetics and electrochemical properties of poly-1, 8-diaminonaphthalene modified electrodes in aqueous acid solutions

606-612The electrochemical behavior and charge transport processes of poly-1 , 8-diaminonaphthalene have been studied by cyclic potential sweep method in aqueous solutions. At scan rates lower than 100 mV/s the film shows semiinfinite diffusion behavior and then the electrode reaction can be considered in the same manner as of a solution phase redox species at an uncoated electrode. The effects of pH and temperature on the peak currents and peak potentials have been studied. The kinetic parameters of polymeric film have been estimated and a redox mechanism of poly-I ,8- diaminonaphthalene film proposed

Simulation of Seepage and Water Tightening Limit in Dam Foundation by Using of Hydro Mechanical Analysis: Upper Gotvand Dam

Seepage and ways of water tightening is one of the fundamental parameters in choosing the situation of large dames. In the field of seepage estimation considering the position of joints because of high capability of fluid flow in comparison to the porosity of the rock is so important. Also fluid of flow in rock mass as a result of changes in aperture of the joints is so impressible of effective stresses exerted on it. In this paper it has been tried to create a 3dimentional model of upper Gotvand dam with capability of hydro mechanical simulation by using of distinct element method, with the results of numerical modeling the water tightening limit was estimated 85 meter and seepage between 3.2 to 16.8 (m3/s)