Pathways and Mechanism of Caffeine Binding to Human Adenosine A2A Receptor

Caffeine (CFF) is a common antagonist to the four subtypes of adenosine G-protein-coupled receptors (GPCRs), which are critical drug targets for treating heart failure, cancer, and neurological diseases. However, the pathways and mechanism of CFF binding to the target receptors remain unclear. In this study, we have performed all-atom-enhanced sampling simulations using a robust Gaussian-accelerated molecular dynamics (GaMD) method to elucidate the binding mechanism of CFF to human adenosine A2A receptor (A2AAR). Multiple 500–1,000 ns GaMD simulations captured both binding and dissociation of CFF in the A2AAR. The GaMD-predicted binding poses of CFF were highly consistent with the x-ray crystal conformations with a characteristic hydrogen bond formed between CFF and residue N6.55 in the receptor. In addition, a low-energy intermediate binding conformation was revealed for CFF at the receptor extracellular mouth between ECL2 and TM1. While the ligand-binding pathways of the A2AAR were found similar to those of other class A GPCRs identified from previous studies, the ECL2 with high sequence divergence serves as an attractive target site for designing allosteric modulators as selective drugs of the A2AAR

Fructosamine: an alternative assessment of past glycaemic control in developing countries

Fructosamine assay determines glycaemic control in diabetic patients by measuring glycosylated plasma protein. This study was done to assess the value of fructosamine as an alternative test to HbA1c as a measure of glycaemia. Sixty patients (both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus) were selected from the diabetic clinic and fasting blood samples were collected for estimation of glucose, HbA1c and fructosamine levels. The results were compared by correlation analysis and major discrepancies/discordance was detected by dividing the results into 3 clinical categories and detecting the cases in which the values fell in opposite clinical categories. Fructosamine correlated well with HbA1c (r = 0.41, p \u3c 0.01) and with fasting blood glucose (r = 0.45 p \u3c 0.01). Major discordance was detected in the results of only 7 patients which can partly be attributed to different periods over which HbA1c and fructosamine reflect average glycaemia. Fructosamine measures glycaemia over the past 2-3 weeks and HbA1c over 8 weeks. As fructosamine assay is relatively inexpensive, reliable and simple to perform; it can be used as an alternative to HbA1c and is particularly suited for developing countries

Food and Nutrition Security in the Rural Plains of Nepal: Impact of the Global Food Price Crisis

Background: Poverty and food insecurity are often associated and may lead to malnutrition. All three remain high in Nepal and may have been aggravated by the 2008 food price crisis. Methods to measure changes in food and nutrition security and track the localised impact of changes in global food prices required further development so as to provide better guidance to policy makers. Aim: To describe and compare measures of poverty and food security in Dhanusha District, Nepal, derived from the Household Economy Approach (HEA) and Household Surveillance Data (HSD), and assess changes in food prices and the affordability of a nutritionally adequate diet among different wealth groups in before, during, and after the 2008 food price crisis. Methods: HEA baseline data collected in 2006 was used to describe livelihoods, food insecurity, and food prices in Dhanusha. Principal Component Analysis was used to generate asset indices from HEA and HSD data and examine their correlations. Additional surveys collected food prices in 2008 and 2009, and data on income levels in 2005 and 2008. Inflation in food prices was estimated using Dhanusha food and beverage index, calculated for 2005, 2008 and 2009 (Sep-Oct). Linear programming was used to estimate the minimum cost of a nutritionally adequate diet in 2005 and 2008 (Sep-Oct). Results: HEA and HSD asset indices were weakly associated. HEA data provided detailed descriptions of the livelihoods of the wealth groups, but underestimated food insecurity. Annual inflation in food prices was much higher (18.8%) in 2009 than average inflation between 2005 and 2008 (9.5%). The nutritionally adequate diet was unaffordable to poorer households in both 2005 and 2008. The situation did not deteriorate much due to increasing levels of household income that accompanied the rise in food prices. Conclusions: Application of the HEA method is demanding on skill and such skills may not be readily transferable. Poorer households are vulnerable to increased food insecurity and malnutrition due to continued increases in food prices after 2008

Multiple-relaxation-time lattice Boltzmann simulation of natural convection flow in a partitioned cavity using GPU computing

© 2019 Author(s). In this paper, we demonstrated the implementation of General Purpose Graphics Processing Unit (GPGPU) programming in Compute Unified Device Architecture (CUDA) C for the simulation of natural convection flow in a side-heated three-dimensional (3D) rectangular cavity with a partition. In the present lattice Boltzmann method (LBM) D3Q19 multiple-relaxation-time (MRT) and D3Q6 single relaxation-time (SRT) model are implemented for the simulation of fluid flow and temperature phenomena, respectively. The parallel code is validated with the benchmark problem of a side heated cubic cavity. The results are presented by the temperature distribution in terms of isotherms, local and average Nusselt number and 3D view of iso-surface for the different Rayleigh number (Ra) and the Prandtl number fixed at Pr = 0.71. It is also observed that the present parallel implementation of the MRT-lattice Boltzmann simulation in GPU has a substantial computational effciency rather than the sequential programming in central processing units (CPU)

Diabetic ketoacidosis in a hospital based population in Pakistan

Sixty-two consecutive episodes of diabetic ketoacidosis (DKA) were studied at Aga Khan University Hospital, Karachi. Forty-four (71%) were type I and 18 (29%) type II diabetics. Mean age was 28.1 years and mean duration of diabetes 4.1 years. Infections were the most common precipitating factor accounting for 28 episodes (45.2%). Twenty-two patients (35.5%) had hyperosmolality (serum osmolality \u3e 320 mosmol/L). Mean serum Na+ was 131.7 mmol/L and K+ 4.6 mmol/L. Twenty-three (37.1%) were hyperkalemic at presentation with seven patients (11.3%) being comatosed and 35 (56.5%) alert. Mean random blood glucose (RBG) was 624 mg/dl, mean pN 7.09, osmolality 316 mosmol/L and the neurological status correlated statistically significantly with mean RBG, pH and osmolality. A leukemoid response was seen in 83.9% episodes. Mortality rate was 8.0% in patients with DKA managed in this hospital

Geographical inequalities in health in a time of austerity: Baseline findings from the Stockton-on-Tees cohort study

Stockton-on-Tees has the highest geographical inequalities in health in England with the life expectancy at birth gap between the most and deprived neighbourhoods standing at over 17 years for men and 11 years for women. In this study, we provide the first detailed empirical examination of this geographical health divide by: estimating the gap in physical and general health (as measured by EQ. 5D, EQ. 5D-VAS and SF8PCS) between the most and least deprived areas; using a novel statistical technique to examining the causal role of compositional and contextual factors and their interaction; and doing so in a time of economic recession and austerity. Using a stratified random sampling technique, individual-level survey data was combined with secondary data sources and analysed using multi-level models with 95% confidence intervals obtained from nonparametric bootstrapping. The main findings indicate that there is a significant gap in health between the two areas, and that compositional level material factors, contextual factors and their interaction appear to be the major explanations of this gap. Contrary to the dominant policy discourse in this area, individual behavioural and psychosocial factors did not make a significant contribution towards explaining health inequalities in the study area. The findings are discussed in relation to geographical theories of health inequalities and the context of austerity

Effect of different sowing dates on yield of tomato genotypes

The experiment was conducted at Agricultural Research Station, Thakurgaon, Bangladesh during October 2009 to March 2010 to observe the effect of sowing dates on yield of tomato genotypes. Three sowing dates viz. October 1, October 15 and October 30 were considered as factor A and tomato variety viz., BARI Tomato-2, BARI Tomato-3, BARI Tomato-4, BARI Tomato-9 and BARI Hybrid Tomato-4 considered as factor B. The experiment was laid out in RCBD (Factorial) with three replications. Early flowering (52.40 days) as well as early fruit harvesting (119.13 days) was occurred in October 1 sowing, where as sowing on October 30 resulted in delayed flowering (71.73 days) and fruit harvesting (140.67 days), respectively. Number of fruits per plant was also the highest (27.40) in October 1 sowing and the lowest (13.73) was in October 30 sowing. Seed sowing of October 1 was found better in respect of yield (74.75 tha-1) compared to October 15 (58.55 tha-1) and October 30 (24.60 tha-1) sowing. Among the variety, BARI Tomat-2 produced the highest (68.12 tha-1) marketable yield followed by BARI Tomato-9 (56.16 tha-1) and BARI Tomato-3 while BARI Tomato-4 gave the lowest (36.91 tha-1) marketable yield. DOI: http://dx.doi.org/10.3329/ijarit.v4i1.21090 Int. J. Agril. Res. Innov. & Tech. 4 (1): 40-43, June, 201

Change in cost and affordability of a typical and nutritionally adequate diet among socio-economic groups in rural Nepal after the 2008 food price crisis

Diet quality is an important determinant of nutrition and food security and access can be constrained by changes in food prices and affordability. Poverty, malnutrition, and food insecurity are high in Nepal and may have been aggravated by the 2008 food price crisis. To assess the potential impact of the food price crisis on the affordability of a nutritionally adequate diet in the rural plains of Nepal, data on consumption patterns and local food prices were used to construct typical food baskets, consumed by four different wealth groups in Dhanusha district in 2005 and 2008. A modelled diet designed to meet household requirements for energy and essential nutrients at minimum cost, was also constructed using the ‘Cost of Diet’ linear programming tool, developed by Save the Children. Between 2005 and 2008, the cost of the four typical food baskets increased by 19% – 26% and the cost of the nutritionally adequate modelled diet increased by 28%. Typical food baskets of all wealth groups were low in macro and micronutrients. Income data for the four wealth groups in 2005 and 2008 were used to assess diet affordability. The nutritionally adequate diet was not affordable for poorer households in both 2005 and 2008. Due to an increase in household income levels, the affordability scenario did not deteriorate further in 2008. Poverty constrained access to nutritionally adequate diets for rural households in Dhanusha, even before the 2008 food price crisis. Despite increased income in 2008, households remain financially unable to meet their nutritional requirements