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.

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.

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.

The World Health Organization Measles Programmatic Risk Assessment Tool-Pilot Testing in India, 2014.

Measles is a leading cause of child mortality, and reduction of child mortality is a key Millennium Development Goal. In 2014, the World Health Organization and the U.S. Centers for Disease Control and Prevention developed a measles programmatic risk assessment tool to support country measles elimination efforts. The tool was pilot tested in the State of Uttarakhand in August 2014 to assess its utility in India. The tool assessed measles risk for the 13 districts of Uttarakhand as a function of indicator scores in four categories: population immunity, surveillance quality, program delivery performance, and threat. The highest potential overall score was 100. Scores from each category were totaled to assign an overall risk score for each district. From this risk score, districts were categorized as low, medium, high, or very high risk. Of the 13 districts in Uttarakhand in 2014, the tool classified one district (Haridwar) as very high risk and three districts (Almora, Champawat, and Pauri Garhwal) as high risk. The measles risk in these four districts was largely due to low population immunity from high MCV1-MCV2 drop-out rates, low MCV1 and MCV2 coverage, and the lack of a supplementary immunization activity (SIA) within the past three years. This tool can be used to support measles elimination in India by identifying districts that might be at risk for measles outbreaks, and to guide risk mitigation efforts, including strengthening routine immunization services and implementing SIAs.

Antibacterial, antioxidant and Immuno-modulatory properties in extracts of Barleria lupulina Lindl.

BACKGROUND: Antibacterial, immunomodulatory and antioxidant properties of aerial parts of Barleria lupulina Lindl were investigated in the present communication. METHODS: The antibacterial, antioxidant and immunomodulatory properties of B. lupulina (methanol soluble leaf and stem extracts) was analyzed by minimum inhibitory concentration, total phenolic contents, DPPH radical scavenging activity, determination of toxicity, hemagglutination antibody titre, delayed type hypersensitivity and neutrophil adhesion test, respectively. RESULTS: Methanol soluble leaf extract (MLE) contains more soluble bioactive compounds inhibiting the growth of five bacterial pathogens viz., Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella typhi even at MICs of 1.25 and 2.5 mg/mL. Aqueous stem extract (ASE) was least effective while MLE was highly effective in inhibiting the growth and survival of bacterial pathogens. While testing the effect of these extracts in animal model, no mortality of albino rats was recorded by using MLE and MSE at the concentrations from 200 to 600 mg/kg of their body weight. The MLE showed significant result in agglutination reaction and induced paw edema volumes when compared with untreated group (control). Both MLE and MSE extracts significantly increased neutrophil adhesion with increase in doses of extracts. MLE was found to have more potent immune-stimulant properties than the MSE. High phenolic contents were found in MSE while lowest IC50 values were found in MLE in term of DPPH radical scavenging activity. CONCLUSIONS: Methanol soluble leaf and stem extract of Barleria lupulina contains antibacterial, antioxidants and immunomodulating phytochemical compounds that was effective for antibacterial, antioxidant and immunomodulatory properties. These may be used as synthetic drug.

Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014.

Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Predictors of COVID-19 positivity among patients presenting to screening clinic in a dedicated COVID-19 hospital, in chandigarh, India - A cross-sectional study.

Background: The aim of this study was to analyze the clinical features of patients attending the screening clinic of a dedicated COVID-19 hospital (DCH), including COVID-19 RT-PCR test positivity rate, symptom predictors for COVID-19 positivity, the proportion of recovery, and the mortality among COVID-19 positive cases. Methods: We conducted a cross-sectional study of the patients who reported in the screening clinic of a DCH. Data were retrieved from medical records. Step-wise binary logistic regression was applied to determine the symptom predictors for determining the likelihood of the suspects turning out to be COVID-19 positive. Results: A total of 573 patients reported to the screening clinic were enrolled, and their median age was 36 ± 14 years. Of the total patients, 237 (41%) were females and 112 (20%) patients were COVID-19 suspects. Fifty (45%) suspects tested COVID-19 positive. The majority of the positives had complaints of cough, fever, and sore throat. Running nose (OR = 7.951) and history of contact with a COVID-19-positive case (OR = 169.9) were found to be statistically significant symptom predictors for COVID-19 positivity. All patients recovered with nil case fatality. Conclusion: Running nose and history of contact with COVID-positive patients were significant predictors for COVID-19 positivity. In this pandemic state, patients who present with any of the upper respiratory infection (URI) symptoms such as cough, sore throat, running nose, headache, and loss of taste/smell should be tested for COVID-19 for early identification and isolation to break the chain of transmission. The public should be encouraged to undergo COVID-19 testing if they develop any of the URI symptoms.

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.

Suicide deaths among medical students, residents and physicians in India spanning a decade (2010-2019): An exploratory study using on line news portals and Google database.

BACKGROUND: Despite having one of the world's largest medical education consortium, India lacks a comprehensive and nationally representative data on suicide deaths among medical students and physicians unlike the one found in most of the developed nations of the world. AIM: We aimed to explore the different characteristics of suicide deaths among medical students, residents and physicians in India over a decade (2010-2019). METHODS: Content analysis of all suicide death reports among medical students, residents and physicians available from online news portals and other publicly available sites was done. Search was done retrospectively using pertinent search words individually or in combination with language restricted to Hindi and English and timed from January 2010 to December 2019. Reports on completed suicide by allopathic medical students, residents and physicians from India were included. Socio-demographic and suicidological variables were analysed using R software. RESULTS: A total of 358 suicide deaths among medical students (125), residents (105) and physicians (128) were reported between 2010 and 2019. Around 7 out of 10 suicides happened before the age of 30 and had mean age 29.9 (±12.2) years. Female residents and physicians were younger than their male counterparts at the time of suicide. Overall maximum suicide deaths were concentrated in South India except the state of Kerala. The specialty of anesthesiology (22.4%) followed by obstetrics-gynaecology (16.0%) had the highest suicide deaths. Violent suicide methods were more commonly used by all, with hanging being the most common mean of suicide. Academic stress among medical students (45.2%) and residents (23.1%), and marital discord among physicians (26.7%) were the most noticeable reasons for suicide. Mental health problems were the next most common reason in medical students (24%) and physicians (20%) while harassment (20.5%) was in residents. Twenty six percent had exhibited suicide warning signs and only 13% had ever sought psychiatric help before ending their lives. A total of nine reports of suicide pact were found with the average deaths per pact being 2.4 and predominantly driven by financial reasons. CONCLUSION: Academic stress among medical students and residents, and marital discord in physicians emerged as the key reasons for suicide. However, this preventable domain should be further explored through focused research. This is the first of its kind study from India which attempted to explore this vital yet neglected public health issue using the most feasible and practical method of online news content-based analysis.

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.