Background: Maternal mortality is a measure of quality of health care in a community. Assam has the highest maternal mortality rate among all India’s states, which is almost double the national average, with around 328 deaths per 100 000 live births. Three quarters of these deaths are among the tea plantations community. It has serious implications on the family, the society and the nation. Maternal mortality rate (MMR) is a very sensitive index that reflects the quality of reproductive care provided to the pregnant women. The objective of the study was to assess the Institutional maternal mortality and the causes of maternal death over a period of a year at a Tertiary Care Teaching Hospital in Dibrugarh district, Assam.Methods: A retrospective hospital based study of maternal death cases from September 2015 to August 2016 was conducted to assess the maternal mortality. The study was carried out in the Obstetrics and Gynaecology Department of Assam Medical College and Hospital (AMCH), Assam. The study included 48 maternal deaths in the year. The information regarding reproductive parameters was collected from the maternal death register and the results were analyzed by using percentage.Results: Out of 9789 total deliveries, Institutional Maternal Mortality was found to be 490 per 1, 00,000 live births. The maternal death was high among the Tea Garden community (66.7%) at the age group 15–20 years and was prevalent mainly in the illiterates (31.3%). Anaemia (29.1%) was the leading cause of death; followed eclampsia (23.0%) and septicaemia (17.0%) while cardio respiratory failure was indirect leading cause for maternal deaths.Conclusions: There is a wide scope for improvement as a large proportion of the observed deaths were preventable. Most maternal deaths can be limited by utilisation of existing medical facilities and identifying the barriers in accessing health delivery system. Early identification of high risk pregnancies and regular ante-natal check up with timely referral to tertiary care centre can help reduce the mortality among the women.
Investigate the protein-ligand binding affinity and evaluate the receptor binding abilities of different classes of ligands for APOE4 through molecular docking studies. The polymorphic nature of human Apo E gene encodes one of 3 common epsilon (ε) alleles (ε2, ε3, and ε4), reported to influence the risk of cardiovascular diseases. Structural basis of APOE4 involvement in CAD suggests that the intramolecular domain interactions to be a suitable target for therapeutic intervention. Identification of APOE4 modulators, targeted towards therapeutic candidates in CAD using Molecular Docking studies. Various classes of ligands including known drugs used in the treatment of CAD, fragment-based stabilizers and their similar structures and molecules with known bioactivity against APOE4 were screened for their binding affinity and further investigated for their interactions with APOE4. Computational studies show the benzyl amide derived structures to be useful candidates in modulation of APOE4. The protein-ligand binding affinities predicted in the study indicated receptor binding abilities of APOE4 that can lead to have interesting insights on structural conformity of APOE4 and its correlated functional aspects. Understanding modulation of APOE4 can pave ways to use it as biomarker for CAD as well as for its therapeutics. Further analysis of the variation of the docked protein structure, molecular dynamic simulation can be performed to generate a dynamic structure for binding analysis.
Background: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32). Aim: The Present study aims to identify a potential inhibition of MMP9, Proteasome, BTK, and TAK1 and also determine the most suitable and effective protein target for the MCL. Methodology: 9 known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), Oprozomib (PubChem ID: 25067547), Zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds. Results : MMP9 inhibitors shows the commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB3CT. The pharmacophore study of the best virtual screened compound reveals the high efficacy of compound based on various interactions. The better affinity of the virtual screened compound with the target MMP9 protein was deduced using toxicity and integration profile studies. Conclusion: On the basis of ADMET profile, compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was also found to be non-toxic with LD50 values for both the compounds lying in the same range.
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Apolipoprotein E (APOE) polymorphism is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The structural features of the isoforms (APOE2, APOE3, and APOE4) differ by only single amino acid that explicate their unique functions as lipid transporter with a role in cholesterol metabolism. It is therefore hypothesized that the cysteine/arginine change at position 112 results in structural differences within APOE3 and APOE4 leading to variation in binding affinities of ligands. We report for the first time computational and structural studies that reveal selectivity amongst ligands for APOE binding, with possible links to CAD pathogenesis. Molecular dynamics study allowed to understand the APOE conformational flexibility and its stability followed by Molecular docking studies that identified scaffold of Ligand 11802 by screening of 22,203 molecules from ChemDiv Library which showed the highest affinity towards APOE4. The ligand showed the presence of chemical moieties, similar to that present in known APOE4 stabilizers in Alzheimer's Disease, which opened a possibility for the ligand as a potential therapeutic agent that could affect the behaviour of APOE4 in CAD pathogenesis. Further, ligand-binding preferences of each isoform with LDL receptors (LDLR) allowed understanding of the in-vivo mechanism in CAD pathogenesis.
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