Development and validation of a questionnaire to assess socio-behavioural impact of COVID-19 on the general population

Background and aimThe aim of the study is to develop a valid and reliable tool to assess sociobehavioural changes due to COVID among the general population.MethodsThis mixed method study has two phases. Phase I for questionnaire development (literature review, focus group discussion, expert evaluation and pilot testing). Phase II for establishing construct validity via factor analysis and internal consistency via Cronbach’s ɑ by administering the questionnaire on 179 participants.ResultsA questionnaire comprising 33 questions and five domains was developed having Cronbach’s α of 0·82.ConclusionThe developed questionnaire is a concise, easy to administer and valid tool to assess socio-behavioural changes.     

Neuro-protective potential of quercetin during chlorpyrifos induced neurotoxicity in rats

Chlorpyrifos (CPF) has been considered as one of the most potent organophosphates and is linked to several neurological disorders. On the other hand, Quercetin is a vital plant flavanoid and has been reported to regulate a number of physiological processes in the central nervous system. The present study was conducted to investigate the protective potential of quercetin during chlorpyrifos induced neurotoxicity. Female Wistar rats weighing 150–200?g were divided into four different groups viz: Normal control, CPF treated (13.5?mg/kg.b.wt. every alternate day), Quercetin treated (50?mg/kg.b.wt./day) and combined CPF and quercetin-treated. All the treatments were carried out for a total duration of eight weeks. Chlorpyrifos treatment showed significant alterations in the cognitive behavior and motor activities of rats, which were appreciably improved upon simultaneous supplementation with quercetin. Further, CPF treatment caused a significant inhibition in the enzyme activities of acetylcholinesterase and choline acetyltransferase, but caused an increase in the levels of acetylcholine in the brain. Further, chlorpyrifos exposure significantly elevated the levels of lipid peroxidation and protein carbonyl contents as well as the activities of catalase, superoxide dismutase, which were interestingly found to be decreased following co-treatment with quercetin. In contrast, CPF treatment decreased the activities of glutathione reductase, transferase, as well as levels of reduced and total glutathione in both the cerebrum and cerebellum but co-administration of quercetin, increased these levels. Chlorpyrifos treatment altered the neuro-histoarchitecture, which showed improvement upon quercetin supplementation. Hence, this study suggests that quercetin can be used as a prophylactic intervention to prevent CPF induced neurotoxicity.     

Novel analogs of sulfasalazine as system xc− antiporter inhibitors: Insights from the molecular modeling studies

System x_c⁻ (Sx_c⁻), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sx_c⁻. However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood–brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure–activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sx_c⁻ antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sx_c⁻ inhibitory activity following in vitro Sx_c⁻ inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.