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1.
Molecules ; 29(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39274984

RESUMEN

Forced intercalation peptide nucleic acids (FIT-PNAs) are DNA mimics that act as RNA sensors. The sensing event occurs due to sequence-specific RNA hybridization, leading to a substantial increase in fluorescence. The fluorophore in the FIT-PNA is termed a surrogate base. This molecule typically replaces a purine in the PNA sequence. BisQ is a surrogate base that connects two quinolines via a monomethine bond. BisQ-based FIT-PNAs have excellent biophysical features that include high brightness and red-shifted emission (λem, max = 613 nm). In this report, we detail two chemical approaches that allow for the facile synthesis of the BisQ PNA monomer. In both cases, the key compound used for the synthesis of BisQ-CH2COOH is the tBu-ester-modified quinoline synthon (compound 5). Subsequently, one method uses the Alloc acid-protected PNA backbone, whereas the other uses the tBu ester-protected PNA backbone. In the latter case, the overall yield for BisQ acid (compound 7) and BisQ PNA monomer syntheses was 61% in six synthetic steps. This is a substantial improvement to the published procedures to date (7% total yield). Lastly, we have prepared an 11-mer FIT-PNA with either BisQ or thiazole orange (TO) and studied their photophysical properties. We find superior photophysical properties for the BisQ FIT-PNA in terms of the brightness and selectivity, highlighting the added value of using this surrogate base for RNA sensing.


Asunto(s)
Ácidos Nucleicos de Péptidos , Quinolinas , Ácidos Nucleicos de Péptidos/química , Ácidos Nucleicos de Péptidos/síntesis química , Quinolinas/química , Quinolinas/síntesis química , ARN/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , ADN/química
2.
Funct Integr Genomics ; 24(5): 167, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298002

RESUMEN

Long COVID (LC) refers to a condition characterized by a variety of lingering symptoms that persist for more than 4 to 12 weeks following the initial acute SARS-CoV-2 infection. Recent research has suggested that the FOXP4 gene could potentially be a significant factor contributing to LC. Owing to that, this study investigates FOXP4's role in LC by analyzing public datasets to understand its evolution and expression in diverse human populations and searching for drugs to reduce LC symptoms. Population genetic analysis of FOXP4 across human populations unmasks distinct genetic diversity patterns and positive selection signatures, suggesting potential population-specific susceptibilities to conditions like LC. Further, we also observed that FOXP4 experiences high expression during LC. To identify potential inhibitors, drug screening analysis identifies synthetic drugs like Glisoxepide, and natural compounds Kapurimycin A3 produced from Streptomyces sp, and Cucurbitacin B from Begonia nantoensis as promising candidates. Overall, our research contributes to understanding how FOXP4 may serve as a therapeutic target for mitigating the impact of LC.


Asunto(s)
COVID-19 , Factores de Transcripción Forkhead , SARS-CoV-2 , Humanos , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , COVID-19/genética , COVID-19/virología , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Biología Computacional/métodos , Evolución Molecular
3.
RSC Adv ; 14(41): 29812-29826, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39301234

RESUMEN

Phase-change memory (PCM) relies on the characteristics of phase-change materials that exhibit slow resistance state changes and enable multilevel operation with minimal resistance drift. They are emerging as promising candidates for artificial intelligence applications inspired by neuroscience and require high volumes of data. However, achieving the necessary qualities, such as thermal stability and fast operation speed, simultaneously is still a major obstacle for PCM materials. The present study investigated the linear and nonlinear optical and electronic properties of Te(1-x)(GeSe0.5)Y x (x = 0.05, 0.1, 0.15) thin films deposited via a thermal evaporation technique by structural characterization (using XRD), surface morphology analysis (using SEM), and elemental composition analysis (using EDX). Transmission spectra ranging from 500 to 2500 nm were obtained using a UV-visible spectrophotometer to determine the optical properties. The refractive index (n) and extinction coefficient (k) were also determined, and Tauc's relationship was applied to assess the optical absorption data. The absorption coefficient (α) was determined utilizing the Urbach relation. The Wemple-DiDomenico model was employed to calculate the nonlinear refractive index. Furthermore, the dielectric properties, loss tangent, and surface/volume energy loss functions were determined. The optical energy bandgap of the thin films revealed the allowed indirect transitions. The observed enhancement of the optical parameters suggested that the investigated composition is appropriate for different photonic applications.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39221671

RESUMEN

Tobacco, being an established risk factor for significant mortality and morbidity, causes over 7 million annual deaths globally. India is a country with over 270 million active tobacco users. On the one hand, although the willingness to quit amongst tobacco users is as high as 55.4%, the actual quit rates translate to less than 20%. Taking a cue from the economic principle of commitment and consistency, paying a nominal fee can serve as a form of public commitment and motivation to decrease the dropout rate amongst those committed to quitting. This study uses contingent valuation assessment to determine the willingness to pay (WTP) values for an effective tobacco cessation service across individuals with different socio-demographic characteristics. A cross-sectional observational study with multistage cluster sampling in Rajasthan was conducted to recruit 360 active tobacco users from 8 districts. Q-Q plots were used to determine the non-parametric distribution, and statistical differences between median WTP values were compared using Mann-Whitney U and Kruskal-Wallis H tests, considering a p-value less than 0.05 to be statistically significant. The majority of participants were males (57.78%) between the ages of 26 and 35 (40.28%), married (82.50%), and with children (65.83%), with an annual income between USD 7500-10,000 (23.61%) and graduate-level education (40.56%). Exclusive smokers formed the majority of the cohort (48.06%), and 50.83% were willing to quit as well as willing to pay for cessation. Median WTP values were maximum for males (USD 54.05; p<0.05), age group 26-35 years (USD 54.05; p<0.05), post-graduates (USD 81.08; p<0.05), and annual income above USD 20,000 (USD 121.62; p<0.05). Weak positive and significant correlations were observed between WTP and annual spending on tobacco, annual spending on health, and annual income. The study emphasizes the critical importance of early-age interventions for effective tobacco cessation prior to transitioning into dependency, resulting in reduced financial parity for availing health services. These are the first such WTP values from the Southeast Asian region, tailored for different population subsets, specifically for tobacco cessation. Our findings contribute to the growing body of evidence to support innovative approaches to enhance tobacco cessation efforts through financial commitments.

5.
BMC Health Serv Res ; 24(1): 989, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187822

RESUMEN

BACKGROUND: Transgender people comprise an estimated 0.3-0.5% (25 million) of the global population. The public health agenda focuses on understanding and improving the health and well-being of gender minorities. Transgender (TG) persons often have complex healthcare needs and suffer significant health disparities in multiple arenas. The international literature suggests that this community is at a higher risk of depression, and other mental health problems, including HIV. Many transgender people experience gender dysphoria and seek specific medical needs such as sex reassignment surgeries, implants, hormonal therapies, etc., but are unable to access these services due to financial or social reasons. The objective of this study was to assess the healthcare needs and associated barriers experienced by transgender people in Western Rajasthan. METHODOLOGY: A qualitative study was carried out in which multilevel stakeholder interviews were conducted using interview and focus group discussion guides. Data was analyzed using the qualitative thematic analysis technique. RESULTS: Findings reveal that transgender people have expressed their need to access health services for general health needs, including but not limited to mental health, non-communicable diseases, and infectious diseases. Barriers to healthcare services were identified on 3 levels: health system, social and personal. Health system barriers include policy, accessibility, affordability, and acceptability issues. Social factors such as inadequate housing, education, and job opportunities also play an important role in affecting the individual's health-seeking behavior. The knowledge of healthcare providers in this context was also limited in context of health insurance schemes, package of services available for transgenders and the importance of gender sensitive healthcare. CONCLUSION: Transgender people expressed the need for mental health services, programs targeting nutritional improvement, gender-affirmation procedures besides regular screening of non-communicable diseases as operational for males and females. Levels of barriers have been identified at various levels ranging from absence of targeted policies to individual behavior.


Asunto(s)
Grupos Focales , Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de Salud , Investigación Cualitativa , Personas Transgénero , Humanos , Personas Transgénero/psicología , Personas Transgénero/estadística & datos numéricos , Masculino , Femenino , Adulto , India , Persona de Mediana Edad , Entrevistas como Asunto , Adulto Joven
6.
Res Sq ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39108482

RESUMEN

Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown. Additionally, it is worth investigating if urate changes after perturbations, such as vaccination, are associated with DNA methylation in a sex-specific manner. Methods: We investigated the association between DNA methylation and serum urate concentrations in a Dutch cohort of 325 healthy individuals. Urate concentration and DNA methylation were measured before and after Bacillus Calmette-Guérin (BCG) vaccination, used as a perturbation associated with increased gout flares. The association analysis included united, interaction, and sex-stratified analysis. Validation of the identified CpG sites was conducted using three independent cohorts. Results: 215 CpG sites were associated with serum urate in males, while 5 CpG sites were associated with serum urate in females, indicating sex-specific associations. Circulating urate concentrations significantly increased after BCG vaccination, and baseline DNA methylation was associated with differences in urate concentration before and after vaccination in a sex-specific manner. The CpG sites associated with urate concentration in males were enriched in neuro-protection pathways, whereas in females, the urate change-associated CpG sites were related to lipid and glucose metabolism. Conclusion: Our study enhances the understanding of how epigenetic factors contribute to regulating serum urate levels in a sex-specific manner. These insights have significant implications for the diagnosis, prevention, and treatment of various urate-related diseases and highlight the importance of personalized and sex-specific approaches in medicine.

7.
Geroscience ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141284

RESUMEN

The number of older adults worldwide is growing exponentially. However, while living longer, older individuals are more susceptible to both non-infectious and infectious diseases, at least in part due to alterations of the immune system. Here, we report on a prospective cohort study investigating the influence of age on immune responses and susceptibility to infection. The RESIST Senior Individuals (SI) cohort was established as a general population cohort with a focus on the elderly, enrolling an age- and sex-stratified sample of 650 individuals (n = 100 20-39y, n = 550 61-94y, 2019-2023, Hannover, Germany). It includes clinical, demographic, and lifestyle data and also extensive biomaterial sampling. Initial insights indicate that the SI cohort exhibits characteristics of the aging immune system and the associated susceptibility to infection, thereby providing a suitable platform for the decoding of age-related alterations of the immune system and unraveling the molecular mechanisms underlying the impaired immune responsiveness in aging populations by exploring comprehensive, unbiased multi-omics datasets.

8.
Indian J Otolaryngol Head Neck Surg ; 76(4): 3338-3344, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39130268

RESUMEN

Background: Voice disorders in occupations connected with excessive voice use can be attributed to the inappropriate use of voice and poor vocal hygiene. Therefore, it is essential for persons in such occupations to be aware of vocal abuse, vocal hygiene, practices and their influence on maintaining healthy voice. Objectives: To assess knowledge, attitude and practice on vocal abuse and vocal hygiene among diverse occupational voice users in Jodhpur. Methodology: A cross-sectional study was conducted in Jodhpur district, Rajasthan. Data was collected from 424 participants (106 Doctors, 106 Teachers, 106 Advocates, 106 Vendors) from May 2023 to July 2023 by administrating a pretested semi structured questionnaire. Microsoft Excel and IBM SPSS (V. 23) statistical software were used for descriptive and inferential statistical analysis. Results: Majority (92%) of the participants felt that their quality of voice was good. About 55% participants were not aware about the term vocal abuse (Doctors 17.9%, Teachers 39.6%, Advocates 79.2%, Vendors 44.3%). Around 56% participants (Doctors 63.3%, Teachers 66.0%, Advocates 32.1%, Vendors 61%) had negative attitude towards vocal hygiene practices. About 47% of the participants preferred home remedies and 44.3% (Doctors 72.6%, Teachers 48.1%, Advocates 41.5%, Vendors 15.1%) preferred to consult ENT specialist for their voice related problem. Perception of vocal abuse on vocal health and hygiene practices was found to statistically significant (p = 0.001) among the different category of occupations. Conclusion: In this perception-based, cross-sectional study it was found that majority of the participants were neither aware about term vocal abuse nor followed vocal hygiene practices. In view of the above findings it is strongly recommended that excessive voice users should be made aware of vocal hygiene practices & repeated reinforcement of the same is required to prevent voice related problem.

9.
Indian J Public Health ; 68(2): 167-174, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38953801

RESUMEN

BACKGROUND: In tuberculosis (TB) care and management, there are practical challenges existing at the patient-provider level leading to implementation barriers at the primary care level. OBJECTIVES: The objective of the study is to explore the challenges and barriers faced by people with TB and health-care workers in TB care and management. MATERIALS AND METHODS: This study was done as a part of a community intervention study between November 2021 and December 2022. Twenty interviews were taken with treatment for TB (n = 7) and health-care personnel (n = 13). Health-care personnel include nursing staff, medical officers, laboratory technicians, community health workers, and medical personnel from tertiary care hospital. Participants were recruited across all levels of health-care systems. Interviews were carried out in the Hindi language, audio recorded, and translated to English. Participants were asked about their experiences of challenges and barriers faced during TB care and management. Qualitative data were coded, and thematic analysis was done manually. RESULTS: The challenges and barriers at the level of people with TB were issues with communication between providers and people with TB, out-of-pocket expenditure, poor adherence to medicines, lack of proper diet, gender issues, and stigma. The challenges and barriers at the level of health-care providers were a lack of infrastructure and logistics, lack of awareness, COVID-19-related issues, lack of workforce, and technical issues. CONCLUSION: Communication between providers and people with TB must be improved to improve the drug adherence and satisfaction of the end user. Proper funding must be provided for the TB programs. People with TB must be counseled properly regarding the free health care services available near their homes to prevent out-of-pocket expenditure. These will help in fast-tracking the elimination of TB.


Asunto(s)
Personal de Salud , Investigación Cualitativa , Tuberculosis , Humanos , Masculino , Femenino , Tuberculosis/terapia , Tuberculosis/tratamiento farmacológico , Personal de Salud/psicología , India , Adulto , Accesibilidad a los Servicios de Salud , Estigma Social , Entrevistas como Asunto , COVID-19 , Gastos en Salud/estadística & datos numéricos , Cumplimiento de la Medicación
10.
Crit Rev Oncog ; 29(4): 43-54, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38989737

RESUMEN

Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , Receptor ErbB-2 , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Animales
11.
Nicotine Tob Res ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38836838

RESUMEN

INTRODUCTION: Indian cigarillos (bidi) are low-cost alternatives to cigarettes with only 22% imposed taxes, and turnover of upto INR 4 million per annum exempted from taxation. This paper estimates revenue implications and potential loss of life years (YLLs) averted, if bidi industry is subjected to increased regulations and taxation. METHODS: Revenue estimated at 10% increased regulation and 100% regulation were calculated, followed by estimates at taxes equivalent to cigarettes and World Health Organization - Framework Convention on Tobacco Control (WHO-FCTC) recommendation. Price elasticity was considered to assess demand. Price change in separate fractions (previously regulated and unregulated) were calculated to obtain potential YLLs averted. RESULTS: Current revenue of USD 59.25 million is projected to increase to USD 179.25 million with 695,159 averted YLLs at cigarette equivalent taxes and 10% increased regulation; USD 639.38 million with 4,527,597 averted YLLs with 100% regulation; USD 54.75 million, at WHO recommended taxes with 2,233,740 YLLs averted at 10% increased regulation, and 10,486,192 YLLs at 100% regulation. CONCLUSION: Proposed estimates are inline with WHO recommendations as they consider price elasticity and suggest substantial increase in revenue, while averting YLLs. A national action is needed to drive the policy decisions towards increased regulation and taxation and revision of India's tobacco control legislation. IMPLICATIONS: Our study presented empirical evidence of how the currently underutilized tool of taxation, as proposed in the WHO-FCTC, can be utilized to decrease bidi smoking prevalence and save measurable life years while generating government revenue simultaneously. While the revenue statistics counter the misleading tobacco industry narratives, the projected reduction in mortality will be seen as an irrefutable driving force for policy reforms, targeted at strategic increase in regulation and taxation of the traditional Indian cigarillos industry.

12.
BMC Geriatr ; 24(1): 519, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877412

RESUMEN

BACKGROUND: The majority of persons with dementia in Sweden reside in their own homes with support from family members. Approximately, 12% of persons with dementia have immigrant background. Within the next 20 years, the number of persons with dementia who are non-ethnic Swedes is said to double. Family caregivers with immigrant backgrounds are noted to receive less support in the community than ethnic Swedes and rate their health status lower than ethnic Swedish peers. The Swedish National Board of Health and Welfare have highlighted the importance of follow-up support for family caregivers with immigrant backgrounds as there is a recognized gap in research and available information tailored to meet the needs of this group. PURPOSE OF THE STUDY: The purpose of the study is to test effectiveness of an mHealth based intervention through which community social workers can improve caregiving competence of non-European immigrant family caregivers of people with dementia living at home in Sweden. The overarching aim is to reduce caregiver burden and depressive symptoms, and improve quality of life. METHODS: A randomized controlled trial (RCT) including wait list control group will be performed consisting of an intervention group (A, n = 44) and a wait list control group (B, n = 44), totaling a sample size of 88. On completion of the 10-weeks long intervention in the intervention group, the intervention will be delivered to group B. Effect of the intervention will be analyzed between and within groups over time. The content of the educational component of the intervention is inspired by the iSupport manual developed by the World Health Organization. The contents, in the form of a booklet, aims to equip the family caregivers with structured information on understanding dementia as a condition and its management at home, including self-care guidance designed specifically for family caregivers themselves. DISCUSSION: Similar telephone-delivered intervention studies targeted for family caregivers to persons with dementia are ongoing in Malaysia and will start in India using the same booklet adapted to the local context. These studies will provide evidence on the effectiveness of using digital technologies to deliver support to those who may not be reached or adequately served by the traditional healthcare system. TRIAL REGISTRATION: ISRCTN registry, Registration number ISRCTN64235563.


Asunto(s)
Cuidadores , Demencia , Telemedicina , Humanos , Cuidadores/psicología , Suecia , Demencia/terapia , Demencia/psicología , Emigrantes e Inmigrantes/psicología , Calidad de Vida/psicología , Femenino , Masculino , Trabajadores Sociales/psicología , Anciano
13.
Curr Obes Rep ; 13(3): 475-495, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38850502

RESUMEN

PURPOSE OF REVIEW: Since the mid-twentieth century, obesity and its related comorbidities, notably insulin resistance (IR) and type 2 diabetes (T2D), have surged. Nevertheless, their underlying mechanisms remain elusive. Evolutionary medicine (EM) sheds light on these issues by examining how evolutionary processes shape traits and diseases, offering insights for medical practice. This review summarizes the pathogenesis and genetics of obesity-related IR and T2D. Subsequently, delving into their evolutionary connections. Addressing limitations and proposing future research directions aims to enhance our understanding of these conditions, paving the way for improved treatments and prevention strategies. RECENT FINDINGS: Several evolutionary hypotheses have been proposed to unmask the origin of obesity-related IR and T2D, e.g., the "thrifty genotype" hypothesis suggests that certain "thrifty genes" that helped hunter-gatherer populations efficiently store energy as fat during feast-famine cycles are now maladaptive in our modern obesogenic environment. The "drifty genotype" theory suggests that if thrifty genes were advantageous, they would have spread widely, but proposes genetic drift instead. The "behavioral switch" and "carnivore connection" hypotheses propose insulin resistance as an adaptation for a brain-dependent, low-carbohydrate lifestyle. The thrifty phenotype theory suggests various metabolic outcomes shaped by genes and environment during development. However, the majority of these hypotheses lack experimental validation. Understanding why ancestral advantages now predispose us to diseases may aid in drug development and prevention of disease. EM helps us to understand the evolutionary relation between obesity-related IR and T2D. But still gaps and contradictions persist. Further interdisciplinary research is required to elucidate complete mechanisms.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Obesidad , Humanos , Diabetes Mellitus Tipo 2/genética , Obesidad/genética , Evolución Biológica , Predisposición Genética a la Enfermedad , Fenotipo , Genotipo
14.
Pathol Res Pract ; 260: 155390, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38878668

RESUMEN

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy with poor prognosis and patient survival outcome. Protein kinase D2 (PKD2) belongs to Ca++/calmodulin-dependent serine/threonine kinase family and its aberrant expression is associated with many cellular and physiological functions associated with tumorigenesis including cell proliferation. We show that PKD2 is activated during G2/M cell cycle transition and its catalytic inactivation by small molecule inhibitor CRT0066101 or genetic knockdown caused suppression of EOC cell proliferation followed by a delay into mitotic entry. Our RNASeq analysis of PKD2-inactivated EOC cells revealed significant downregulation of genes associated with cell cycle including Aurora kinase A, a critical mitotic regulator. Mechanistically, PKD2 positively regulated Aurora kinase A stability at both transcriptional and post-translational levels by interfering with the function of Fbxw7, drove G2/M cell cycle transition and EOC cell proliferation. Moreover, pharmacological inhibition of Aurora kinase A by small molecule CD532 or its shRNA-mediated genetic knockdown suppressed EOC cell proliferation, induced G2/M cell cycle arrest and mitotic catastrophe followed by apoptosis. Taken together, our results indicated that PKD2 positively regulates Aurora kinase A during G2/M cell cycle entry and pharmacological targeting of PKD2/Aurora kinase A signalling axis could serve as a novel therapeutic intervention against a lethal pathology like EOC.


Asunto(s)
Aurora Quinasa A , Carcinoma Epitelial de Ovario , Proliferación Celular , Neoplasias Ováricas , Proteína Quinasa D2 , Transducción de Señal , Humanos , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/metabolismo , Femenino , Proliferación Celular/efectos de los fármacos , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/genética , Aurora Quinasa A/metabolismo , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa A/genética , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Pirimidinas/farmacología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/genética , Inhibidores de Proteínas Quinasas/farmacología
15.
J Mol Model ; 30(5): 122, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38570356

RESUMEN

CONTEXT: In this study, we have investigated the structure, reactivity, bonding, and electronic transitions of DPA and PDTC along with their Ni-Zn complexes using DFT/TD-DFT methods. The energy gap between the frontier orbitals was computed to understand the reactivity pattern of the ligands and metal complexes. From the energies of FMO's, the global reactivity descriptors such as electron affinity, ionization potential, hardness (η), softness (S), chemical potential (µ), electronegativity (χ), and electrophilicity index (ω) have been calculated. The complexes show a strong NLO properties due to easily polarization as indicated by the narrow HOMO-LUMO gap. The polarizability and hyperpolarizabilities of the complexes indicate that they are good candidates for NLO materials. Molecular electrostatic potential (MEP) maps identified electrophilic and nucleophilic sites on the surfaces of the complexes. TDDFT and NBO analyses provided insights into electronic transitions, bonding, and stabilizing interactions within the studied complexes. DPA and PDTC exhibited larger HOMO-LUMO gaps and more negative electrostatic potentials compared to their metal complexes suggesting the higher reactivity. Ligands (DPA and PDTC) had absorption spectra in the range of 250 nm to 285 nm while their complexes spanned 250 nm to 870 nm. These bands offer valuable information on electronic transitions, charge transfer and optical behavior. This work enhances our understanding of the electronic structure and optical properties of these complexes. METHODS: Gaussian16 program was used for the optimization of all the compounds. B3LYP functional in combination with basis sets, such as LanL2DZ for Zn, Ni and Cu while 6-311G** for other atoms like C, H, O, N, and S was used. Natural bond orbital (NBO) analysis is carried out to find out how the filled orbital of one sub-system interacts with the empty orbital of another sub-system. The ORCA software is used for computing spectral features along with the zeroth order regular approximation method (ZORA) to observe its relativistic effects. TD-DFT study is carried out to calculate the excitation energy by using B3LYP functional.

16.
Paediatr Anaesth ; 34(7): 665-670, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38661287

RESUMEN

BACKGROUND: The purpose of this study is to provide comprehensive and efficient pre-anesthesia counseling (PAC) utilizing audiovisual aids and to examine their effect on parental anxiety. METHODS: For this prospective, controlled study, 174 parents were recruited and randomized into three groups of 58 (Group A: video, Group B: brochure, and Group C: verbal). During pre-anesthesia counseling, the parent was provided with a detailed explanation of preoperative preparation, fasting instructions, transport to the operating room, induction, the emergence of anesthesia, and nursing in the post-anesthesia care unit based on their assigned group. We evaluated parental anxiety using Spielberger's State-Trait Anxiety Inventory before and after the pre-anesthesia counseling. RESULTS: The results of our study show a statistically significant difference in the final mean STAI scores among the three groups (Group A: 34.69 ± 5.31, Group B: 36.34 ± 8.59, and Group C: 43.59 ± 3.39; p < .001). When compared to the brochure and verbal groups, the parents in the video group have the greatest difference in mean baseline and final Spielberger's State-Trait Anxiety Inventory scores (12.207 ± 5.291, p .001). CONCLUSION: The results of our study suggest that pre-anesthesia counseling by video or a brochure before the day of surgery is associated with a higher reduction in parental anxiety when compared to verbal communication.


Asunto(s)
Ansiedad , Comunicación , Consejo , Folletos , Padres , Cuidados Preoperatorios , Humanos , Ansiedad/prevención & control , Ansiedad/psicología , Padres/psicología , Femenino , Cuidados Preoperatorios/métodos , Masculino , Estudios Prospectivos , Consejo/métodos , Anestesia/métodos , Grabación en Video , Recursos Audiovisuales , Adulto , Niño , Preescolar
17.
Sci Rep ; 14(1): 5381, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443485

RESUMEN

The qualitative and quantitative assessment of groundwater is one of the important aspects for determining the suitability of potable water. Therefore, the present study has been performed to evaluate the groundwater quality for Achhnera block in the city of Taj, Agra, India, where groundwater is an important water resource. The groundwater samples, 50 in number were collected and analyzed for major ions along with some important trace element. This study has further investigated for the applicability of groundwater quality index (GWQI), and the principal component analysis (PCA) to mark out the major geochemical solutes responsible for origin and release of geochemical solutes into the groundwater. The results confirm that, majority of the collected groundwater samples were alkaline in nature. The variation of concentration of anions in collected groundwater samples were varied in the sequence as, HCO3- > Cl- > SO42- > F- while in contrast the sequence of cations in the groundwater as Na > Ca > Mg > K. The Piper diagram demonstrated the major hydro chemical facies which were found in groundwater (sodium bicarbonate or calcium chloride type). The plot of Schoellar diagram reconfirmed that the major cations were Na+ and Ca2+ ions, while in contrast; major anions were bicarbonates and chloride. The results showed water quality index mostly ranged between 105 and 185, hence, the study area fell in the category of unsuitable for drinking purpose category. The PCA showed pH, Na+, Ca2+, HCO3- and fluoride with strong loading, which pointed out geogenic source of fluoride contamination. Therefore, it was inferred that the groundwater of the contaminated areas must be treated and made potable before consumption. The outcomes of the present study will be helpful for the regulatory boards and policymaker for defining the actual impact and remediation goal.

18.
Nanoscale ; 16(8): 4176-4188, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38323839

RESUMEN

Triboelectric nanogenerators have the ability to harvest low- and mid-frequency vibrational energy from the environment; however, achieving stable performance of the nanogenerator device in high-temperature conditions remains challenging. In this work, a flexible and temperature-stable polyvinyl alcohol (PVA)/layered double hydroxides (LDH) nanocomposite-based triboelectric nanogenerator was developed to harvest unexploited vibrational energy for the first time. Crystalline ZnAl LDH nanosheets grown by a hydrothermal route are used to fabricate the high-performance flexible nanogenerator. The ZnAl LDH exhibits fire-retardancy and high-temperature stability (∼500 °C). A triboelectric nanogenerator based on the ZnAl LDH-PVA nanocomposite generated a very high output voltage of 60 V even under a low vertical pressure of 1 kgf. Surprisingly, the developed device shows ultra-stable output performance even up to a temperature of 200 °C. In addition, a ZnAl LDH-nanosheet-reinforced PVA nanocomposite film shows very high dielectric constant of about 5 × 105 at the low-frequency side. The tremendous increase in the output voltage and stable performance are discussed in terms of the high dielectric constant and synergistic effect of the LDH nanosheets and PVA. Furthermore, the device was also used to monitor human body movements such as finger and wrist bending to develop self-powered sensors.

19.
BMC Public Health ; 24(1): 527, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378536

RESUMEN

BACKGROUND: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.


Asunto(s)
Diabetes Gestacional , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/diagnóstico , Embarazo , Femenino , Prevalencia , India/epidemiología
20.
JNMA J Nepal Med Assoc ; 62(270): 68-71, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38409988

RESUMEN

Introduction: Birth asphyxia causes significant morbidity and mortality among neonates, especially in low-income and middle-income countries like Nepal. However, there is a paucity of data regarding its burden. This study aimed to find the prevalence of birth asphyxia among neonates admitted to the neonatal intensive care unit of a tertiary care hospital. Methods: This descriptive cross-sectional study was conducted among neonates at a tertiary care hospital between 15 January 2022 to 14 January 2023 after obtaining ethical approval from the Institutional Review Committee. Neonates with gestational age ≥35 weeks were included and those with major congenital anomalies were excluded. A convenience sampling method was used. A point estimate was calculated at a 95% Confidence Interval. Results: Among 902 neonates, 120 (13.30%) (11.08-15.52, 95% Confidence Interval) had birth asphyxia. A total of 108 (90%) were outborn, and 84 (70%) were males. HIE stage-I, II and III were seen in 47 (39.17%), 64 (53.33%) and 9 (7.50%) of the asphyxiated neonates respectively. Poor suck 92 (76.67%), seizures 73 (60.83%) and lethargy 70 (58.33%) were common abnormal neurological findings. Death occurred in 15 (12.50%) neonates in the hospital. Conclusions: The prevalence of birth asphyxia was found to be similar to other studies done in similar settings. The high burden underscores an urgent need to implement better perinatal care and delivery room management practices. Keywords: hypoxic-ischemic encephalopathy; neonates; prevalence.


Asunto(s)
Asfixia Neonatal , Unidades de Cuidado Intensivo Neonatal , Recién Nacido , Masculino , Embarazo , Femenino , Humanos , Lactante , Estudios Transversales , Centros de Atención Terciaria , Asfixia , Asfixia Neonatal/epidemiología
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