Srimanta Sankaradeva University of Health Sciences, Guwahati, Assam, India is established in 2009 as per The Srimanta Sankaradeva University of Health Sciences Act, 2007. The Srimanta Sankaradeva University of Health Sciences is the only Health Sciences University in the North Eastern Region with its jurisdiction to the whole of Assam.
Abstract The global rise in malaria mortality is significantly influenced by the increasing resistance of Plasmodium falciparum to widely used and affordable antimalarial drugs, among other contributing factors, emphasizing the need for novel therapeutic agents. In this study, a series of 84 quercetin-derived ligands were designed and subsequently evaluated in silico as potential inhibitors of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS; PDB ID: 1J3K), a validated antimalarial drug target. Virtual screening and molecular docking were performed using AutoDock implemented in PyRx v0.8, followed by molecular dynamics simulations using GROMACS v2024.4. Pharmacokinetic and toxicity profiles were assessed using SwissADME and Protox 3.0. Molecular docking identified 35 designed compounds exhibiting higher predicted binding affinities than the reference drugs cycloguanil (− 6.0 kcal/mol) and pyrimethamine (− 5.2 kcal/mol), with ligand binding energies ranging from − 5.8 to − 9.8 kcal/mol. Among these, ligand b.II exhibited the most favorable predicted binding affinity (− 9.8 kcal/mol) and was selected for further molecular dynamics simulations which indicated stable ligand–protein interactions, with minor differences in dynamic behavior compared to the reference drug, pyrimethamine. ADME analysis of the 35 selected compounds indicated that most of them exhibited favorable pharmacokinetic properties, as reflected by acceptable molecular weight, hydrogen bond donors and acceptors (nHBD, nHBA), lipophilicity (iLogP), and topological polar surface area, along with compliance with drug-likeness parameters such as number of Lipinski rule of five violations and synthetic accessibility, while toxicity studies predicted the ligands to have a low risk of hepatotoxicity, cardiotoxicity, and carcinogenicity. Overall, the findings support the potential of quercetin derivatives, particularly b.II, for further investigation. However, given that these results are derived from computational analyses, experimental validation is necessary to confirm their antimalarial efficacy against multidrug-resistant Plasmodium falciparum.
The global rise in malaria mortality is largely driven by the increasing resistance of Plasmodium falciparum to widely used and affordable antimalarial drugs, emphasizing the urgent need for novel therapeutic agents. In this study, thirty-five ligands were computationally evaluated as potential inhibitors of the bifunctional enzyme dihydrofolate reductase–thymidylate synthase (DHFR-TS; PDB ID: 1J3K), a validated antimalarial drug target. Virtual screening and molecular docking were performed using AutoDock implemented in PyRx v0.8, followed by molecular dynamics simulations using GROMACS v2024.4. Pharmacokinetic and toxicity profiles were assessed using SwissADME and Protox 3.0. ADME analysis revealed favorable pharmacokinetic properties for most compounds, while toxicity predictions classified the majority into Classes IV and V, indicating low acute toxicity, with all promising ligands predicted to be non-hepatotoxic, non-cardiotoxic, and non-carcinogenic. Among the evaluated compounds, six ligands (b.II, b.III, b.VIII, I.b, II.b, and VII.b) exhibited higher binding affinities toward DHFR-TS than the reference drugs cycloguanil and pyrimethamine. These ligands formed strong hydrogen bonding and van der Waals interactions with key active-site residues, including SER A:167, LEU A:40, ILE A:14, LEU A:164, ASN A:33, THR A:36, GLU A:25, and CYS A:27, contributing to enhanced binding stability. Notably, ligand b.II demonstrated the strongest binding affinity and sustained stability, identifying it as a promising lead candidate for further experimental validation against multidrug-resistant Plasmodium falciparum.
OBJECTIVE:To identify the risk factors for intrapartum stillbirth and examine whether these are different from that of antepartum stillbirth, and investigate the survival probabilities of fetuses by gestational age in high-risk pregnancies. METHODS:We conducted a secondary data analysis of a hospital-based cohort study from India, including 9774 singleton pregnancies from 13 hospitals across six states. We conducted modified Poisson regression analysis to assess associations between potential risk factors and intrapartum stillbirth. Kaplan-Meier survival curves were used to explore survival probabilities of fetuses among pregnant women who had anemia and hypertensive disorders in pregnancy (HDP) compared with those who did not have these problems. RESULTS:There were 167 intrapartum stillbirths and 9607 live births; representing an incidence of 17.1 per 1000 total births (95% confidence interval [CI]: 14.6-19.9). Risk factors identified were illiteracy (adjusted risk ratio [aRR]: 2.37, 95% CI: 1.33-4.38), age > 34 years (aRR: 3.17, 1.41-7.36), <4 antenatal check-ups (aRR: 1.90, 1.27-2.87), <100 days of iron and folic acid supplementation (aRR: 9.10, 4.15-21.05), other HDP (aRR: 2.48, 1.36-4.25), severe anemia (aRR: 3.33, 1.82-6.63), preterm birth (aRR: 3.25, 2.26-4.69) and <10th percentile birth weight-for-gestational age (aRR: 1.57, 1.14-2.17). These were similar to the risk factors for antepartum stillbirths. Survival probabilities for fetuses among women with pre-eclampsia/eclampsia and severe anemia decreased from 34 weeks' and 30 weeks' gestation, respectively. CONCLUSION:In this high-risk hospital cohort of pregnant women undergoing labor induction or augmentation, risk factors for intrapartum stillbirth overlapped substantially with those for antepartum stillbirth, although the antepartum analysis was underpowered. Targeted monitoring of women with severe anemia and HDP from 30 weeks may reduce intrapartum stillbirth risk in similar settings.
IntroductionMyocardial ischemia–reperfusion injury (IRI) continues to impede the advancement of effective cardioprotective therapies. Experimental limitations, particularly the lack of accessible and cost-effective ex vivo platforms, restrict mechanistic and translational research. This study aimed to develop a simplified, resource-conscious proof-of-concept ex vivo rat heart perfusion model capable of inducing key features of myocardial IRI, rather than establishing a fully validated replacement for conventional Langendorff systems.MethodsTwelve adult male Wistar rats were randomly assigned to a non-ischemic control group (n = 6) or an IRI group (n = 6). Following a 10 min stabilization period, hearts in the IRI group underwent 30 min of global ischemia using potassium-based Krebs–Henseleit buffer (KHB) cardioplegic solution, followed by 60 min of reperfusion. Control hearts received continuous perfusion without ischemic insult. Coronary flow was assessed to evaluate functional changes. Myocardial injury was quantified using triphenyl tetrazolium chloride (TTC) staining, and structural alterations were examined through histopathological analysis.ResultsThe IRI group demonstrated an approximately 4.7-fold reduction in coronary flow during early reperfusion, reflecting acute vascular dysfunction. TTC staining revealed significant infarct development compared to controls. Histopathological examination confirmed cardiomyocyte degeneration, cytoplasmic vacuolization, inflammatory cell infiltration, and interstitial edema. Functional impairment strongly correlated with structural myocardial injury, demonstrating consistent induction of myocardial injury within the experimental setting.DiscussionThis simplified ex vivo model reproduces fundamental features of myocardial IRI within a resource-conscious framework. However, it should be interpreted as a proof-of-concept platform rather than a replacement for conventional Langendorff systems.
Introduction: Essential Newborn care is a comprehensive strategy to reduce the death of newborn through effective interventions before conception during pregnancy, immediately after birth and postnatal period1 . These will contribute to sustained reduction in neonatal mortality. Objectives: To evaluate the effect of Structured Teaching Program (STP) on Knowledge and Practices of Essential Newborn Care (ENBC) among Post-Natal Mothers admitted in the selected government hospital of Kamrup (M), Assam. Material and Methods: The study was conducted using Pre-experimental One group pre-test post- test design research design with a total of 35 Post-Natal Mothers by purposive sampling. Data was collected by interview with selfstructured questionnaire for knowledge and checklist to assess the Practice of Essential Newborn Care. Results: The findings revealed 6% of Post Natal Mother had inadequate knowledge, 63% had moderately adequate knowledge and 31 % had adequate knowledge in the pre test where as in the post test 100% of Post Natal Mothers had adequate knowledge regarding Essential Newborn Care. 3% Post Natal Mother had poor practice, another 86% average practice and another 11% Post Natal Mother had good practice on Essential Newborn Care in pretest whereas in post test 14% of Post Natal Mother had average practice and majority 86% of them had good practice on Essential Newborn Care. Post test Practices score were higher than pre test Practices score on Essential Newborn care. The data also shows that the‘t’ value for knowledge is (t=11.75), p <0.05 and‘t’ value for practices are (t=9.743), p value <0.05 is highly significant at 0.05 level of significance. Conclusion: In conclusion, the study revealed that the structured teaching program proved highly effective in significantly improving knowledge and practice of Post Natal Mothers on Essential New Born Care.
