Repurposing of USFDA-approved drugs to identify leads for inhibition of acetylcholinesterase enzyme: a plausible utility as an anti-Alzheimer agent.

In the quest to identify new anti-Alzheimer agents, we employed drug repositioning or drug repositioning techniques on approved USFDA small molecules. Herein, we report the structure-based virtual screening (SBVS) of 1880 USFDA-approved drugs. The in silico-based identification was followed by calculating Prime MMGB-SA binding energy and molecular dynamics simulation studies. The cumulative analysis led to identifying domperidone as an identified hit. Domperidone was further corroborated in vitro using anticholinesterase-based assessment, keeping donepezil as a positive control. The analysis revealed that the identified lead (domperidone) could induce an inhibitory effect on AChE in a dose-dependent manner with an IC50 of 3.67 µM as compared to donepezil, which exhibited an IC50 of 1.37 µM. However, as domperidone is known to have poor BBB permeability, we rationally proposed new analogues utilizing the principles of bioisosterism. The bioisostere-clubbed analogues were found to have better BBB permeability, affinity, and stability within the catalytic domain of AChE via molecular docking and dynamics studies. The proposed bioisosteres may be synthesized in the future. They may plausibly be explored for their implication in the developmental progress of new anti-Alzheimer agent achieved via repurposing techniques in future.

Prevalence of HIV Self-Testing Among Men Who Have Sex With Men: Evidence Synthesis by Systematic Review and Meta-Analysis.

HIV self-testing (HIVST) plays a significant role in addressing the health care needs of high-risk populations, particularly men who have sex with men (MSM). The present systematic review and meta-analysis provide an assessment of the prevalence of HIVST among MSM within the last 5 years. Seven databases (PubMed, Web of Science, Cochrane, Scopus, EMBASE, ProQuest, and EBSCOhost) were searched systematically from January 1, 2018 to March 10, 2023. After an independent search and quality assessment, the pooled prevalence was calculated using a random-effects model. Eight relevant studies were finally included in our study from an initial pool of 288 articles identified through a systematic search. Our meta-analysis revealed that the pooled prevalence of HIVST among MSM is 8% (95% CI: 5%-14%). Significant heterogeneity was noticed among the studies, with an I2 value of 99% and a 95% prediction interval of 3% to 11%. Geography emerged as a significant moderator of this heterogeneity (p < .001). Specifically, studies from China reported a notably higher prevalence of 20% (15%-26%), while other countries reported a lower prevalence of 5% (3%-6%). A symmetrical Doi plot with a Luis-Furuya-Kanamori (LFK) index of -0.57 indicated no publication bias. HIVST has a low take-up among MSM globally. Factors leading to variation in HIVST need to be studied. The coordinated efforts of policymakers, health care providers, and affected communities are required in HIVST promotion.

Cardiovascular risk assessment using non-laboratory based WHO CVD risk prediction chart with respect to hypertension status among older Indian adults: insights from nationally representative survey.

Introduction: Knowledge of the risk of developing cardiovascular diseases (CVD) in the population is an important risk management strategy for the prevention of this disease. This is especially true for India, which has resource-restrained settings with an increased risk in a younger population for the development of the disease. An important modifiable risk factor for CVD is hypertension, with its influence on the development of CVD. Methods: The data from the first wave of the Longitudinal Ageing Study in India (LASI) was used to calculate the 10-year CVD Risk Score among older adults ≥45 years using a WHO (2019) non-laboratory- based chart for South Asia. Univariate analysis was done using Pearson's chi-square test, and multivariable analysis using ordinal logistic regression. Categories of CVD risk score were considered as dependent variable. Socio-demographic variables, regular exercise, history of diabetes and hyperlipidaemia were considered as the independent variables. Relationship between CVD Risk score and hypertensives and self-reported hypertensives were presented using restricted cubic splines. Result: Two-thirds (68.8%) of the population had a 10-year CVD risk of <10, and 2.8% had a risk of ≥20%. The self-reported hypertensives were distributed linearly in restricted cubic splines, with a more scattered distribution in higher scores, while actual hypertensives showed a sigmoid pattern. Urban residents (OR-0.88), being unmarried (OR-0.86), being in the richer (OR-0.94) and richest (OR-0.86) monthly per capita expenditure (MPCE) quintile and exercising regularly (OR-0.68) decreased the odds of being in a higher CVD risk score. Less than primary schooling (1.21) and diabetics (1.69) had higher odds for a higher CVD risk score. Conclusion: In this population, two-thirds had <10% risk for the development of CVD. The study shows a higher risk among rural, poor, and those with a lower education and lower CVD risk for those undertaking physical activity. The sigmoid pattern in actual hypertensives highlights the need for early detection. Even those with undiagnosed hypertension but with a higher BP had a similar risk for disease development, thus highlighting the need for an early detection of hypertension.

Exploring anticancer properties of the phytoconstituents and comparative analysis of their chemical space parameters with USFDA-approved synthetic anticancer agents.

The present review article thoroughly analyses natural products and their derived phytoconstituents as a rich source of plausible anticancer drugs. The study thoroughly explores the chemical components derived from various natural sources, thus emphasizing their unique structural characteristics and therapeutic potential as an anticancer agent. The review contains the critical chemical constituents' in-depth molecular mechanisms, their source's chemical structures and the categories. The review also comprises an exhaustive and comprehensive analysis of different chemical spacing parameters of the anticancer agents derived from natural products. It compares them with USFDA-approved synthetic anticancer drugs up to 2020, thus providing a meaningful understanding of the relationship between natural and synthetic compounds portraying the anticancer assets. The review also delves more deeply into the chemical analysis of the heterocyclic moieties from the natural product arena, illustrating the anticancer mechanisms. The present article is, therefore, expected to serve as a valuable resource for natural product and medicinal chemists, encouraging and promoting an integrated approach to exploit the potential of natural products in drug discovery development and translational research, which have a prerequisite of bench to bedside approach. The work could guide researchers toward innovative approaches for the ever-evolving field of anticancer drug discovery.

Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity.

Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael's addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.

Internet Addiction and Its Association with Demographic Variables, Depression, Anxiety, and Psychological Well-being in College Students.

Background: Internet is an integral part of the daily life of everyone. Internet addiction (IA) is one of the major concerns, specifically among young adults. The association between IA, depression, anxiety, and psychological well-being (PWB) is least studied in young adults. Purpose: To evaluate IA and its association with psychological morbidity and PWB in a larger sample size. In addition, to examine the factors that are associated with IA. Methods: A total of 1287 young students were evaluated in the present study. Participants were evaluated on the Internet Addiction Test (IAT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Psychological Well-Being Index-22. Results: The mean age of the study's participants is 19.5 years. The majority were female (68.9%), from nuclear families (61.8%), and belonged to urban localities (61.5%). On IAT, 15.9% had a presence of IA with a cut-off score of 50. 27.4% and 20.5% had a presence of depression and anxiety with a cut-off score of 10 on the PHQ-9 and GAD-7, respectively. Approximately two-thirds (66.7%) reported poor PWB. IA had a significant positive association with depression and anxiety and a negative association with PWB. Male students, the presence of depression, anxiety, and poor PWB were independent factors associated with IA. Conclusion: Internet addiction is highly prevalent among college students and has a significant association with anxiety, depression, and poor PWB. There is a need to develop a structured plan, educational strategy, and program to minimize IA in young adults.

Outbreak investigation of acute febrile illness from the Himalayan foothills: Solving the puzzle of fever.

In September 2022, Panchkula Civil Hospital reported an outbreak of acute febrile illness (AFI) in Pinjore, located in the Himalayan foothills, Haryana, North India. There was an upsurge of fever cases. Blood samples were taken from suspected patients (n = 58) with AFI and subjected to serology of dengue, chikungunya, Japanese encephalitis, leptospira and scrub typhus. The samples were also screened for West Nile & Zika virus RNA using real-time PCR. Viral strains were characterized by sequencing. Of the 58 cases of AFI, Dengue could be identified in 45 (77.58%) followed by JE and Chikungunya in 2 cases each (3.44%), respectively. Among Dengue positive cases, 44 had monoinfection (97.77%) and 1 patient had dengue and JE. None were positive for Zika, West Nile, Scrub typhus, and Leptospira with the testing protocol. Four patients developed dengue with warning signs, such as abdominal pain in one patient and recurrent vomiting in the remaining three. The dengue serotype could be determined in 17 samples and revealed serotype 2. Molecular evolution analysis based on the complete envelope gene revealed that all DENV-2 strains (n = 13) circulated in the outbreak area belonged to the DENV-2 cosmopoliton genotype. In the early stages of infection, relying only on clinical manifestations is ineffective, so both molecular and serological assays along with clinical diagnosis are noteworthy for determining the aetiology of AFI.

Awareness Regarding Antimicrobial Resistance and Antibiotic Prescribing Behavior among Physicians: Results from a Nationwide Cross-Sectional Survey in India.

(1) Background: Understanding the physicians' knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic.

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure-Activity Relationship Studies.

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression.

An Evaluation of Malaria Surveillance System in Punjab, India, 2020.

Background: India accounted for 6% of global burden of malaria with 95% population residing in malaria endemic areas. However, Punjab is in the malaria elimination phase with annual parasite incidence (API) <1/1000 population. Objectives: We evaluated malaria surveillance system in Punjab using CDC's updated guidelines for evaluating public health surveillance systems to provide recommendations for strengthening the existing system and to overcome the challenges in the path of malaria free Punjab. Methods: We chose two districts of Punjab, Amritsar (lowest API) and Mansa (highest API), interviewed stakeholders, and performed a retrospective desk review. We evaluated the overall usefulness of the system and assessed seven attributes at state, district, health facility, and village level during July-August 2020. Results: In Punjab, there was progressive decline in the malaria cases from 2,955 cases in 2009 to 1,140 in 2019 and no malaria deaths since 2011. Regarding various attributes, overall score for flexibility was good (85.9%); average for simplicity (77%), acceptability (74%), data quality (74%), and timeliness (70%); and poor for representativeness (59%) and stability (57%). Conclusions: Malaria surveillance system was useful in analyzing the trends of morbidity and mortality and for generating data to drive policy decisions. To improve stability, representativeness, and acceptability, surveillance staff should not be engaged in supplemental work, and reports from private sector must be ensured. Supportive supervision and regular trainings should be carried out regarding reporting formats, guidelines, and timely epidemiological investigations to improve timeliness, data quality, and simplicity.

Psychological distress and related factors regarding COVID-19 among the ancillary hospital staff: A cross-sectional study.

Background: Healthcare workers (HCWs) are at the front line of the Coronavirus disease (COVID-19) outbreak response. They have faced great risks to both physical and mental health. We aimed to assess the psychological effect of COVID-19 among ancillary hospital staff. Methods: A cross-sectional study was conducted among 267 on-duty ancillary hospital staff using a semi-structured questionnaire to assess their psychological status and risk perception. In addition, their knowledge, attitude, and practices (KAP) and risk perception were also assessed. The General Health Questionnaire (GHQ-12) was used to screen for psychological distress. Results: Among 267 participants, the mean (±SD) age was 33.5 (7.6) years. The majority knew about the symptoms of COVID-19 (88.4%), droplet spread (99.3%), and the importance of isolation (99.3%). About 35.2% were worried about infecting family members, while 26.2% were worried about colleagues at the frontline. Only 38.9% of them had a good knowledge score. Participants with high school and above education level had significantly good knowledge about COVID-19 (OR = 1.99; 95% CI = 1.17- 3.39) than those with primary school or below. Being female (OR 1.99; 95% CI 1.17-3.39) and working with COVID-19 patients (OR 3.88, 95% CI 1.77-8.47, P = 0.001) was associated with psychological distress. Conclusion: The ancillary hospital staff had insufficient knowledge regarding the risk factors of COVID-19 but possessed positive attitudes and practices. Continued health education and appropriate psychological interventions may improve understanding and reduce psychological distress.

Efficacy and safety of pan-genotypic sofosbuvir and velpatasvir in patients with hepatitis C and HIV coinfection on dolutegravir-based antiretroviral therapy.

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.

Impact of virtual continued medical education on carbon footprint and awareness of digital sobriety: A retrospective cross-sectional study among public health professionals in India.

Background: Due to the COVID-19 pandemic, physical meetings and continuing medical education (CMEs) are being conducted in virtual mode. Digital sobriety has been advocated as a strategy for controlling the environmental emission from online events. The present study was undertaken to assess the impact of virtual CMEs on the environment and the participants' perception, knowledge, attitude, and practices of digital sobriety during the CMEs. Methods: A retrospective cross-sectional Google form-based online study was conducted among the 1,311 registrants of 23 virtual CMEs hosted in India. A pre-tested English questionnaire was used to collect the data. The potential carbon footprint of the significant physical CME activities and the carbon emission (CE) of the virtual CMEs were estimated. Among the registrants contacted, 251 consented and participated in the study. Results: The CE of the virtual CMEs was 0.787 metric tons of carbon dioxide equivalent (MT CO2 Eq). If the CMEs were conducted physically, the potential CE was estimated to be 290.094 MT CO2 Eq. The awareness rate of digital sobriety was 35%. Most of the participants (58.7%) from the current study preferred the hybrid mode of CMEs. Conclusions: Virtual, digitally sober CMEs have reduced the potential CE by 99.7% compared to physical CMEs in India. The awareness and knowledge about digital sobriety is low in India. Knowledge, networking, social interactions, and overall satisfaction were relatively lower in the virtual mode of CMEs than in the physical mode.

Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches.

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33-6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Human rabies control in the era of post-COVID-19: a call for action.

Following the COVID-19 pandemic, there has been a sharp increase in rabies cases and deaths. Rabies outbreaks are being reported worldwide. Multiple disruptions in Rabies control occurred during the pandemic, significantly affecting lower-income countries. Countries need to develop specific action plans to become 'rabies free' by 2030.

Comprehensive assessment of age-specific mortality rate and its incremental changes using a composite measure: A sub-national analysis of rural Indian women.

Background: Diverse socio-economic and cultural issues contribute to adverse health outcomes and increased mortality rates among rural Indian women across different age categories. The present study aims to comprehensively assess age-specific mortality rates (ASMR) and their temporal trends using a composite measure at the sub-national level for rural Indian females to capture cross-state differences. Materials and methods: A total of 19 states were included in the study to construct a composite age-specific mortality index for 2011 (base year) and 2018 (reference year) and examine the incremental changes in the index values across these years at the sub-national level in India. Sub-index values were calculated for each component age group and were subsequently used to compute the composite ASMR index using the geometric mean method. Based on the incremental changes, the performance of states was categorized into four different typologies. Results: Improvement in mortality index scores in the 0-4 years age group was documented for all states. The mortality rates for the 60+ age group were recorded to be high for all states. Kerala emerged as the overall top performer in terms of mortality index scores, while Bihar and Jharkhand were at the bottom of the mortality index table. The overall mortality composite score has shown minor improvement from base year to reference year at all India level. Conclusion: An overall reduction in the mortality rates of rural Indian women has been observed over the years in India. However, in states like Bihar and Jharkhand, mortality is high and has considerable scope for improvement. The success of public health interventions to reduce the under-five mortality rate is evident as the female rural mortality rates have reduced sizably for all states. Nevertheless, there is still sizable scope for reducing mortality rates for other component age groups. Additionally, there is a need to divert attention toward the female geriatric (60+ years) population as the mortality rates are still high.

COVID-19 vaccination uptake and adverse events following COVID-19 immunization in pregnant women in Northern India: a prospective, comparative, cohort study.

Objectives: The most commonly used vaccine in India, Covishield, is a recombinant adenovirus vector vaccine for which safety data in pregnant women are not available. The present study was conducted to assess the uptake of COVID-19 vaccines and monitor adverse events following COVID-19 immunization among pregnant women in northern India. Patients and Methods: A prospective cohort study was conducted among pregnant women registered with the antenatal clinics in Chandigarh Union Territory (U.T.) in northern India. The study included 247 pregnant women and a comparative group of age-matched, non-pregnant women (247) who received the first dose of the COVID-19 vaccine and were followed up by telephone interviews for adverse events following immunization at three time points until 28 days after vaccination. Multivariate regression (logistic and linear) was used for the adjusted analysis, with adverse events following immunization and the duration of adverse events following immunization as the outcomes. Results: The COVID-19 vaccination uptake rate was 66.8% among the pregnant women. The 28-day incidence rate of adverse events following immunization among the pregnant women was 76.5%. The overall 28-day incidence of adverse events following immunization in pregnant women did not differ significantly from that of non-pregnant women (P=0.153). Conclusion: The Covishield vaccine is safe for pregnant women in India. Further follow-up of the cohort for feto-maternal outcomes needs to be conducted with an adequate sample size to confirm the overall safety profile of the vaccine.

Trends in willingness to receive COVID-19 vaccines among healthcare workers in India: Findings from repeated cross-sectional national surveys.

Background: COVID-19 vaccination of the healthcare workers (HCWs) is a key priority in the fight against the SARS-CoV-2 pandemic. India launched its COVID-19 vaccination program in January 2021. We aimed to understand the trends in willingness to receive COVID-19 vaccines and its associated factors among HCWs in India. Methods: Using a repeated cross-sectional survey design, we collected information from HCWs in three critical time points: before (n = 937, October 2020), during (n = 1346, January 2021); and after (n = 812, May 2021) the introduction of COVID-19 vaccines in India. The third survey coincided with the peak of the second wave of COVID-19 pandemic in India. Findings: Of the study participants, 43.7, 60.2, and 73.2% were willing to receive COVID-19 vaccines during the first, second and third rounds of surveys, respectively. In multivariable logistic regression analysis, participants who trusted the health care system were more likely to report willingness to receive a COVID-19 vaccine; medical trust emerged as a significant factor in all the three rounds of surveys (First survey-aOR: 2.24, 95% CI: 1.67-2.99; Second survey-aOR: 3.38, 95% CI: 2.64-4.33; Third survey-aOR: 2.54, 95% CI: 1.65-3.91). Having confidence in domestic vaccines (Second survey-aOR: 2.21, 95% CI: 1.61-3.02; Third survey-aOR: 2.05, 95% CI: 1.24-3.37); and high perceived risk of contracting COVID-19 (Second survey-aOR: 1.48, 95% CI: 1.13-1.93; Third survey-aOR: 2.02, 95% CI: 1.31-3.13) were found to be associated with willingness to receive vaccines. Among socio-demographic characteristics, being married (aOR: 1.71, 95% CI: 1.08-2.71) and having high socio-economic status (aOR: 3.01, 95% CI: 1.65-5.51) emerged as significant factors associated with willingness to receive COVID-19 vaccines in the third round of the surveys. Interpretation: Willingness to receive COVID-19 vaccine increased with time, as the severity of the pandemic increased. To increase COVID-19 acceptance and coverage among HCWs, it is important to instill confidence in domestic vaccines and assist in accurate assessment of risk toward contracting COVID-19 infection.

Neuronal cell death mechanisms in Alzheimer's disease: An insight.

Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid ß peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-ß plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer's Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD.