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1.
Chem Biol Drug Des ; 103(6): e14561, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38862268

RESUMO

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.


Assuntos
Antineoplásicos , Produtos Biológicos , Humanos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Descoberta de Drogas , Estados Unidos , United States Food and Drug Administration
2.
Bioorg Chem ; 147: 107363, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657527

RESUMO

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.


Assuntos
Antioxidantes , Dipeptidil Peptidase 4 , Hipoglicemiantes , Pirazóis , Triazóis , alfa-Amilases , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/síntese química , Relação Estrutura-Atividade , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Dipeptidil Peptidase 4/metabolismo , Estrutura Molecular , Humanos , Relação Dose-Resposta a Droga , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/síntese química , Simulação de Acoplamento Molecular , Picratos/antagonistas & inibidores , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Compostos de Espiro/síntese química , Oxindóis/farmacologia , Oxindóis/química , Oxindóis/síntese química , Benzopiranos , Nitrilas
3.
Ann Neurosci ; 31(1): 21-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38584979

RESUMO

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.

4.
Front Pharmacol ; 14: 1159377, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954851

RESUMO

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.

5.
Antibiotics (Basel) ; 12(10)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37887197

RESUMO

(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.

6.
Pharmaceutics ; 15(9)2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37765177

RESUMO

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.

7.
Indian J Community Med ; 48(3): 407-412, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469921

RESUMO

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.

9.
J Viral Hepat ; 30(9): 740-745, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37260083

RESUMO

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.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Sofosbuvir/efeitos adversos , Antivirais/efeitos adversos , Hepacivirus/genética , Coinfecção/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Genótipo , Resultado do Tratamento
10.
J Family Med Prim Care ; 12(4): 694-700, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37312788

RESUMO

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.

11.
Front Public Health ; 11: 1118685, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36992884

RESUMO

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.


Assuntos
COVID-19 , Educação Médica Continuada , Humanos , Estudos Transversais , COVID-19/prevenção & controle , Pegada de Carbono , Pandemias , Dióxido de Carbono , Saúde Pública , Estudos Retrospectivos
12.
J Travel Med ; 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36715149

RESUMO

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.

13.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677860

RESUMO

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.


Assuntos
Antineoplásicos , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Tubulina (Proteína)/metabolismo , Simulação de Acoplamento Molecular , Proliferação de Células , Quinoxalinas/farmacologia , Colchicina/farmacologia , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/química , Ensaios de Seleção de Medicamentos Antitumorais
14.
Front Med (Lausanne) ; 9: 1046072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523773

RESUMO

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.

15.
J Rural Med ; 17(4): 228-235, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36397796

RESUMO

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.

16.
Front Public Health ; 10: 994206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262227

RESUMO

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.


Assuntos
COVID-19 , Vacinas contra Influenza , Humanos , Vacinas contra COVID-19/uso terapêutico , Pandemias , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Aceitação pelo Paciente de Cuidados de Saúde , Pessoal de Saúde
17.
Front Mol Neurosci ; 15: 937133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090249

RESUMO

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.

18.
Clin Epidemiol Glob Health ; 17: 101113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935532

RESUMO

Background: Vaccine hesitancy is of considerable concern as it threatens the great potential of a vaccine against COVID-19. This study aims to determine factors associated with community health workers' willingness to participate in clinical trials of COVID-19 vaccine, and their vaccination intention, in India. Methods: A cross-sectional study was conducted among 377 community health workers using self-administered anonymous questionnaire during the lockdown periods in India. Participant's socio-demographics, willingness-to-participate in COVID-19 vaccine trials, intention to accept COVID-19 vaccine were recorded in a Likert scale. Data were analysed descriptively, and a multivariate logistic regression model was used to investigate factors associated with willingness to participate and accept the vaccine. Results: Among 377 CHWs, 70 (19%) intended to participate in COVID-19 vaccine trial, 151 (40%) responded positively regarding their intention to get vaccinated. Those with knowledge on development of COVID-19 vaccine [aOR 3.05 (95% CI: 1.18-7.88), p = 0.021], and men [aOR 3.69 (95% CI: 1.51-8.97), p = 0.004] were more willing to participate in clinical-trial, while an undergraduate degree, and trust in domestic vaccines were identified as deterrents for the same. Perceiving COVID-19 as risk [aOR 2.31 (95% CI: 1.24-4.31), p = 0.009], and male gender [aOR 2.39 (95% CI: 1.17-4.88), p = 0.017] were factors associated with intention to get vaccinated. Respondents who had knowledge about COVID-19 virus were less likely to uptake the hypothetical vaccine [aOR 0.32 (95% CI: 0.12-0.88), p = 0.027]. Conclusions: Increasing knowledge regarding COVID-19 is not enough to improve vaccine acceptance rates. Targeted interventions addressing socio-demographic determinants related to COVID-19 vaccination should help improve acceptance.

19.
Front Med (Lausanne) ; 9: 806702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35665354

RESUMO

Background: Despite the success of adult vaccination against COVID-19, providing vaccines to children remains a challenge for policymakers globally. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination in India. Methods: A cross-sectional web-based study was designed, parents or caregivers (N = 770) were recruited through snowball sampling using Google form. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with sociodemographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior. Multivariable logistic regression analysis was performed to compute the predictors of child vaccination intention among Indian parents. Results: Seven hundred and seventy parents across the country have completed the survey. Of the 770 participants, 258 (33.5%) have shown intent to vaccinate their children. The stated likelihood of child vaccination was greater among parents who had a bachelor's degree or higher education (aOR: 1.98, 95% CI: 1.15-3.51); as well as among parents who intended to vaccinate themselves (aOR: 2.35, 95% CI: 1.30-4.67). Parental concerns centered around vaccine safety and side effects. Conclusion: Indian parents reported high knowledge of the COVID-19 virus and were aware of the development of a vaccine. However, about one-third of parents intended to vaccinate their children, and about half of them were not sure whether to vaccinate their children or not against the COVID-19 virus. The study highlighted the need for health promotion strategies that promote vaccine uptake among parents.

20.
Front Public Health ; 10: 870880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734756

RESUMO

Background: Responding to the fast transmission rates and increasing fatality rates, countries across the world expedited the development and deployment of the vaccine for coronavirus disease 2019 (COVID-19). Evaluation of individuals' willingness to pay (WTP) would provide pertinent information regarding future demand and financing preferences, which shall help to devise the effective payment strategy for COVID-19 vaccination. Methods: A nationwide, cross-sectional, and self-administered online survey using a structured questionnaire was conducted to identify the sociodemographic determinants of willingness and extent to pay for COVID-19 vaccine in India. A non-probability convenience sampling followed by snowball sampling was employed to recruit participants (n = 3,341). The likelihood of sociodemographic determinants to predict willingness and extent to pay was modeled using the multivariate binary logistic regression analysis. Results: Out of 3,341 participants, 68% (n = 2,271) were willingness to pay for COVID-19 vaccine. Results showed significantly higher odds for willingness to pay among participants who were single [adjusted odds ratio (aOR) = 1.394, p < 0.01] and having a family size of 4 members (aOR = 1.346, p < 0.01). The adjusted odds ratio sizably increased from 1.396 for participants whose monthly income was between INR 10,000 and 20,000/month to 2.240 for participants whose monthly income was above INR 50,000/month. Further, out of 2,271 of those participants who were willingness to pay for COVID-19 vaccine, majority (n = 1,246, 54.9%) of participants were willingness to pay below 50% of COVID-19 vaccine cost. This study found that those who are single (aOR = 0.688, p < 0.01), having an income between INR 20,000 and 50,000/month (aOR = 0.686, p < 0.05), and those who belonged to socially disadvantaged category (aOR = 0.450, p < 0.01) were estimated to have significantly lower odds of willingness to pay more than 50% of COVID-19 vaccine cost. Conclusion: This study observed that majority of those participants who willingness to pay for COVID-19 vaccine were willingness to pay only up to 50% of COVID-19 vaccine and income was observed as a precursor predictor of the willingness and extent to pay for COVID-19 vaccine. The understanding on the willingness and extent to pay for COVID-19 vaccine and its sociodemographic determinants will be helpful for making the strategic decisions related to the financing of COVID vaccine in India.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Humanos , Inquéritos e Questionários , Vacinação
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