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1.
J Prosthodont ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088703

ABSTRACT

PURPOSE: The objective was the comparison of an occlusal device (OD), and sleep hygiene and progressive muscle relaxation (SH & PMR) on perceived stress and sleep bruxism activity (burst/episode and episode/hour) in participants with sleep bruxism. MATERIAL AND METHODS: Sixty-six participants with self-reported sleep bruxism were selected and randomly allocated into two groups: OD group or SH & PMR group. Assessment of perceived stress and sleep bruxism activity were the primary outcomes. The Perceived Stress Scale-10 (PSS-10 scale) was used to measure perceived stress and bruxism episodes/hour and bursts/episode recorded by electromyography of masseter and temporalis. These outcomes were assessed at baseline, 1 month, 6 months, and 1 year. The paired t-test assessed changes in PSS-10 scores and sleep bruxism activity within the same group over different time points (baseline, 1 month, 6 months, and 1 year). The unpaired t-test compared scores between two groups (OD and SH & PMR) at each time point to evaluate intervention differences. The chi-square test compared gender distribution between both groups. RESULTS: PSS-10 scores were found to decrease with the OD at 1 month and 6 months compared to baseline and SH & PMR at all subsequent follow-ups. This decrease was not statistically significant (p > 0.05) between the OD and SH & PMR groups at all follow-ups. OD and SH & PMR significantly reduced bruxism episodes/hour and bursts/episode at all follow-ups (p < 0.05). There were no adverse effects related to any intervention. CONCLUSIONS: The OD and SH & PMR both effectively reduced PSS-10 scores over 6 months and significantly decreased bruxism episodes and bursts per episode. Both methods are safe and effective for managing sleep bruxism and reducing stress.

2.
Aging Clin Exp Res ; 36(1): 158, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088148

ABSTRACT

BACKGROUND: Population ageing represents a significant global challenge, particularly pronounced in countries like India. AIMS: This study aims to explore how factors such as socio-economic status, behaviour, and health influence healthy ageing across the Indian older population. METHODS: In this study, we utilized the Longitudinal Ageing Study in India - wave 1 dataset for analysis purposes. Scores were generated for five dimensions of healthy aging, including physical, functional, mental, cognitive, and social aspects and these scores were treated as the target variables. Multivariate Regression Trees analysis was employed to identify the behavioural and socio-demographic factors associated with each dimension of healthy ageing. RESULTS: Years of education emerge as crucial across all dimensions, positively impacting cognitive health and mitigating age-related decline in healthy ageing. Marital status, engagement in household activities, spiritual practices, and living arrangements impacts the scores of different aspects of healthy ageing. Gender disparities in healthy aging are noticeable in the 60-74 age group, with women generally having lower scores. Safety of the living environment is a crucial determinant of the mental health of the elderly across all age groups.These findings highlight the complex interplay of factors in healthy ageing outcomes. CONCLUSION: Our study emphasizes the pivotal role of education in fostering healthy ageing in India. Factors such as environmental safety and social participation also influence well-being. Targeted interventions addressing education, gender equality, safety, and healthcare access are vital for enhancing the ageing experience and overall well-being of older adults.


Subject(s)
Healthy Aging , Humans , India , Male , Female , Healthy Aging/physiology , Healthy Aging/psychology , Aged , Middle Aged , Longitudinal Studies , Aging/physiology , Mental Health , Multivariate Analysis , Socioeconomic Factors , Aged, 80 and over , Cognition/physiology , Educational Status , Health Status
3.
Eur J Ophthalmol ; : 11206721241272182, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105228

ABSTRACT

PURPOSE: To study cases diagnosed of myelinated retinal nerve fibres (MRNF) continuous with the optic disc and describe the plausible pathogenic mechanism for the ocular features in Straatsma syndrome. METHODS: This retrospective observational study includes clinically diagnosed MRNF cases. MRNF, myopia, and amblyopia defined Straatsma syndrome. MRNF were classified into three types based on location: type 1 in the superior retina, type 2 in the superior and inferior retina, and type 3 in the inferior retina. MRNF size was measured on Optomap® (Optos, Daytona, UK) images and posterior staphyloma location was noted. Demographics and best-corrected refractive error in logMAR units was recorded. Descriptive statistics and Spearman's corelation test were used to analyse MRNF size's relationship to refractive error and logMAR visual acuity. RESULTS: The study included a total of 19 MRNF eyes from 18 patients. Seventeen (89%) eyes had Straatsma syndrome. Median age was 23.50 [range: 4-75] years. One (6%) patient exhibited bilateral presentation. The median logMAR visual acuity was 0.4 log units (interquartile range: 0.18-1.20) and mean refractive error was -7.21 ± 5.32. Type 2 MRNF (n = 14,74%) was the commonest. Average MRNF size was 34.37 ± 40.73 sq.mm. Posterior staphyloma was noted in 17 eyes, all in close MRNF association. Significant positive corelation was noted between logMAR visual acuity and MRNF size (r = 0.5, p = 0.028). CONCLUSION: Large size MRNF corelated with poor visual acuity in the study. The paper explains the possible pathogenetic mechanisms for the ocular findings seen in MRNF.

4.
Int Arch Otorhinolaryngol ; 28(3): e400-e406, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38974634

ABSTRACT

Introduction Eagle syndrome is a rare and an often misdiagnosed entity in otorhinolaryngology. Objective To determine the efficacy of the surgical treatment for Eagle syndrome. Methods The present prospective study included 25 patients who presented with complaints of pain in the throat, ear, and neck, as well as difficulty and/or pain while swallowing; they were assessed for Eagle syndrome. As per patient profile, we performed a clinical assessments along with orthopantomograms (OPGs), three-dimensional computed tomography (3D CT) scans, and cone beam computed tomography (CBCT). Pain was assessed pre- and postoperatively through the Numerical Rating Scale-11 (NRS-11), whose score ranges from 0 to 10. Microscopic tonsillo-styloidectomy was performed in cases in which the conservative treatment failed to relieve pain. Results The mean age of the entire study population was of 36.08 ± 7.19 years, and the male-to-female ratio was of 1.08:1. Referred otalgia was the commonest (44%) complaint. Radiologically, out of 25 patients, 20 patients presented elongated styloid processes. The longest symptomatic styloid process measured radiographically was of 64.7 mm while the shortest was of 28.2 mm. Out of 20 patients, 12 underwent surgery. The postoperative pain assessment through the NRS-11 was performed on day 0 (3.83 ± 0.83), day 7 (1.5 ± 0.52), week 4 (0.5 ± 0.52), and week 12 (0.41 ± 0.51). By 12 weeks, 7 patients were symptom-free, while 5 patients still reported mild pain. Conclusion Eagle syndrome associated with an elongated styloid process is not a rarity, but it often goes undiagnosed. Microscopic tonsillo-styloidectomy shows excellent results in the management of patients with Eagle syndrome.

5.
Am J Biol Anthropol ; : e24992, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949078

ABSTRACT

This synthesis explores specific ethical questions that commonly arise in isotopic analysis. For more than four decades, isotope analysis has been employed in archeological studies to explore past human and animal dietary habits, mobility patterns, and the environment in which a human or animal inhabited during life. These analyses require consideration of ethical issues. While theoretical concepts are discussed, we focus on practical aspects: working with descendant communities and other rights holders, choosing methods, creating and sharing data, and working mindfully within academia. These layers of respect and care should surround our science. This paper is relevant for specialists in isotope analysis as well as those incorporating these methods into larger projects. By covering the whole of the research process, from design to output management, we appeal broadly to archaeology and provide actionable solutions that build on the discussions in the general field.

6.
Article in English | MEDLINE | ID: mdl-38958673

ABSTRACT

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

7.
Explor Target Antitumor Ther ; 5(3): 766-779, 2024.
Article in English | MEDLINE | ID: mdl-38966175

ABSTRACT

Aim: Supratentorial ependymoma (STE) is a rare tumor with distinct genetic alterations, whose imaging features have been scarcely studied. This study aims to review the computed tomography (CT) and magnetic resonance imaging (MRI) features of a cohort of histopathologically proven STE to identify the distinguishing features of STE, and look for specific signs of zinc finger translocation associated (ZFTA) fused STEs. Methods: Ethical clearance was obtained from the institutional ethics committee. The magnetic resonance (MR) images, CT images when available, clinical details, and pathological reports of 25 patients from a single institute with histopathologically proven STE were retrospectively reviewed. Imaging features, demographic details, pathological and molecular features, and type of surgical resection were described and tabulated. Relevant associations with imaging features were computed and tabulated. Results: The study showed that STEs are common in the pediatric population with no sex predilection. The periventricular location was the most common. A significant association between periventricular location and the presence of a cystic component (P value = 0.023) and the presence of the periwinkle sign/stellate sign (P value = 0.045) was found. Common features of ZFTA fused STEs included periventricular or intraventricular location, cystic component, necrosis, and the periwinkle sign. A significant association was found between ZFTA fusion and cystic component (P value = 0.048). Conclusions: This study attempts to identify the imaging features of STEs and their associations with molecular pathology and surgical outcome, and the distinguishing features of ZFTA fused STEs.

8.
Noncoding RNA ; 10(4)2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39051375

ABSTRACT

The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) are short non-coding RNAs that regulate various biological processes by modulating gene expression. While differential expression of specific miRNAs has been observed in women suffering from recurrent miscarriages, paternal miRNAs remain unexplored. We hypothesize that analyzing sperm miRNAs can provide crucial insights into the pathophysiology of iRPL. Therefore, this study aims to identify dysregulated miRNAs in the spermatozoa of male partners of iRPL patients. Total mRNA was extracted from sperm samples of iRPL and control groups, followed by miRNA library preparation and high-output miRNA sequencing. Subsequently, raw sequence reads were processed for differential expression analysis, target prediction, and bioinformatics analysis. Twelve differentially expressed miRNAs were identified in the iRPL group, with eight miRNAs upregulated (hsa-miR-4454, hsa-miR-142-3p, hsa-miR-145-5p, hsa-miR-1290, hsa-miR-1246, hsa-miR-7977, hsa-miR-449c-5p, and hsa-miR-92b-3p) and four downregulated (hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-519a-2-5p, and hsa-miR-520b-5p). Functional enrichment analysis revealed that gene targets of the upregulated miRNAs are involved in various biological processes closely associated with sperm quality and embryonic development.

9.
Viruses ; 16(7)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-39066193

ABSTRACT

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides' immunogenic potential, which needs to be validated in different experimental systems.


Subject(s)
Molecular Docking Simulation , Nucleocapsid Proteins , Peptides , Puumala virus , Puumala virus/immunology , Puumala virus/genetics , Peptides/immunology , Peptides/chemistry , Humans , Nucleocapsid Proteins/immunology , Nucleocapsid Proteins/chemistry , Nucleocapsid Proteins/genetics , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, B-Lymphocyte/chemistry , Hemorrhagic Fever with Renal Syndrome/immunology , Hemorrhagic Fever with Renal Syndrome/virology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/immunology , Toll-Like Receptor 4/chemistry , Computational Biology , Conserved Sequence , Amino Acid Sequence , Protein Binding
10.
Pharm Dev Technol ; 29(6): 639-647, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38980085

ABSTRACT

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.


Subject(s)
Administration, Intranasal , Biological Availability , Brain , Doxepin , Drug Carriers , Lipids , Nanostructures , Animals , Doxepin/pharmacokinetics , Doxepin/administration & dosage , Brain/metabolism , Lipids/chemistry , Drug Carriers/chemistry , Rats , Male , Nanostructures/chemistry , Particle Size , Drug Delivery Systems/methods , Rats, Sprague-Dawley , Drug Liberation , Biopharmaceutics/methods , Nasal Mucosa/metabolism
11.
Cureus ; 16(6): e63212, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39070429

ABSTRACT

INTRODUCTION: The Uniform Determination of Death Act (UDDA) ensures that individuals with irreversible cessation of circulatory, respiratory, or brain functions receive timely palliative care. Our research has focused on identifying disparities in mortality among individuals with Down syndrome (DS) based on gender, age, racial groups, and geographic regions within the United States over 22 years. This study aims to analyze differences in the location of death, including hospitals, nursing homes, hospice care facilities, and unspecified locations, considering demographic and regional variables. METHODOLOGY: Utilizing a cross-sectional observational study design, we extracted data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) database, specifically targeting deaths coded under the International Classification of Diseases, 11th Revision (ICD-11) code "Q-90." This analysis, covering 1999 to 2020, segmented the data by age, gender, race, and United States Census regions. Death locations were categorized into home/hospice, medical facilities, and nursing/other facilities. Data analysis was conducted using Microsoft Excel, and the Autoregressive Integrated Moving Average (ARIMA) model was applied for statistical assessments. RESULTS: Our analysis included 22604 deaths related to DS, as recorded in the CDC-WONDER database from 1999 to 2020. The majority of these deaths occurred in medical or nursing facilities, with home or hospice deaths accounting for 6106 cases and other locations for 5.29% of deaths. Univariate logistic regression was used to identify predictors of home or hospice deaths, revealing a trend of increasing deaths in these settings over time. CONCLUSIONS: Between 1999 and 2020, there was a notable increase in the number of individuals with DS dying at home or in hospice care, especially among those aged 55-64. Female individuals and those identified as white experienced higher mortality rates than other demographic groups. This shift highlights the need to understand the disparity in places of death within this population, ensuring equitable access to quality end-of-life care for all individuals with DS.

12.
Med J Armed Forces India ; 80(4): 404-411, 2024.
Article in English | MEDLINE | ID: mdl-39071760

ABSTRACT

Adenoid cystic carcinoma (ACC) is an uncommon tumor that usually appears in the major salivary glands of the head and neck region, including the minor glands in the oral cavity, sinonasal tract, and other sites. ACC of the head and neck may have a low-grade histological appearance. This malignant tumor has unusual clinical characteristics such as occasional regional lymph node metastases and a prolonged yet continuously advancing clinical course. Additionally, it is an invasive tumor with perineural invasion, difficult-to-clear margins, metastasis, and localized recurrence. The cribriform and tubular proliferation of basaloid cells, which mostly display a myoepithelial cellular phenotype, are ACC's distinct histologic characteristics. The degree of genetic alterations and aneuploidy observed in tumor genomes are linked to the severity of histologic grade, which correlates with clinical prognosis. The three predominant cell types (PCTs) i.e., conventional ACC (C-ACC), myoepithelial-predominant ACC (M-ACC), and epithelial-predominant ACC (E-ACC)-and their respective applications will be reviewed. The function of extracellular matrix (ECM) components such as laminin, type IV collagen, fibronectin, and tenascin are also emphasized. An attempt has been made to explore the recent molecular diversity, regulatory pathways prevalent in PCT, ECM with its genetic changes, and translational utility with targeted therapies for ACC.

13.
Nanoscale Adv ; 6(15): 3714-3732, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39050960

ABSTRACT

DNA nanostructures have surfaced as intriguing entities with vast potential in biomedicine, notably in the drug delivery area. Tetrahedral DNA nanostructures (TDNs) have received worldwide attention from among an array of different DNA nanostructures due to their extraordinary stability, great biocompatibility, and ease of functionalization. TDNs could be readily synthesized, making them attractive carriers for chemotherapeutic medicines, nucleic acid therapeutics, and imaging probes. Their varied uses encompass medication delivery, molecular diagnostics, biological imaging, and theranostics. This review extensively highlights the mechanisms of functional modification of TDNs and their applications in cancer therapy. Additionally, it discusses critical concerns and unanswered problems that require attention to increase the future application of TDNs in developing cancer treatment.

14.
Indian J Psychol Med ; 46(4): 305-312, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39056034

ABSTRACT

Background: Nomophobia is a situational phobia evoked by unavailability of smart phone or the thought of the possibility of not having it, not being able to use it and losing it. Currently used instruments for assessment of severity of nomophobia offers challenges of administration and have limited applicability in the Indian setting. Therefore, this study was aimed to depict and understand the lived experience of college students with nomophobia and making sense of it. Methods: This interpretative phenomenological analysis research design study was carried out on 17 undergraduate students belonging to different academic streams including Science, Social science and Commerce from the three study sites situated in different locations of India. An in-depth interview guide was prepared. The students who scored more than 90 on nomophobia questionnaire (NMP-Q Questionnaire) were included in the study. The data was recorded in audio and video format, it was transcribed, and translated from Hindi to English language. Coding was done and the theme were extracted. Results: The findings identified six superordinate themes: Digital Obsession, Digital Compulsion, Approval Motivation, Digital Intensement, Digital Well-being and Insight. Conclusion: The lived experiences of the students with nomophobia had explicitly shown a strong inclination towards the smartphone. They also focused on some of the significant aids provided by the smartphone. Further the intensive use of the smartphone was posing major challenges to the students when they were away from it.

15.
J Clin Gastroenterol ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39042482

ABSTRACT

Despite advancements in treatment strategies, the mortality from colorectal cancer (CRC) remains high. Evidence suggests that aspirin (ASA) may have a protective effect on CRC incidence and metastasis through various mechanisms. The 2016 to 2020 National Inpatient Sample was used to identify adult patients (age above 18 y) with the principal diagnosis of CRC. Patients were stratified into 2 groups based on ASA use. The outcomes studied were in-hospital mortality and rates of total, gastrointestinal (GI), non-GI, and lymphoid metastasis. A multivariate logistic regression analysis was performed to evaluate the impact of ASA use on outcomes after adjusting for patient demographics, comorbidities, and the Elixhauser Comorbidity Index (ECI). Of the 814,270 patients, 88,620 (10.8%) used ASA, with the majority being aged above 65 years (78%), male (57%), white (77.6%), and had Medicare insurance (74.5%). There was a higher prevalence of Diabetes mellitus, Hypertension, Chronic pulmonary disease, Coronary artery disease, Chronic kidney disease, Chronic heart failure, Obesity, and Smoking among aspirin users than among non-ASA users. Patients who used ASA had a lower prevalence of total (47.3% vs. 32.5%, P<0.001), GI (22.2% vs. 32.4%, P<0.001), non-GI (9.9% vs. 15.3%, P<0.001), and lymphoid (9.3% vs. 10.9%, P<0.001) metastasis compared with those who did not use ASA. After adjusting for confounding factors, patients with ASA use had lower odds of total (aOR: 0.75, 95% CI: 0.72-0.78, P<0.001), GI (aOR: 0.74, 95% CI: 0.71-0.77, P<0.001), non-GI (aOR: 0.72, 95% CI: 0.68-0.77, P<0.1), and statistically insignificant odds of lymphoid (aOR: 0.95, 95% CI: 0.90-1.00, P=0.098) metastasis. The use of ASA is associated with a decrease in the prevalence of metastasis among individuals diagnosed with CRC, but additional studies are required to elucidate the mechanism and duration of therapy needed to be effective.

16.
Nature ; 631(8022): 876-883, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38987605

ABSTRACT

Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance1. In addition to genetic mutations2, recent research has identified a role for non-genetic plasticity in transient drug tolerance3 and the acquisition of stable resistance4,5. However, the dynamics of cell-state transitions that occur in the adaptation to cancer therapies remain unknown and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell-state transitions accompanied by a progressive increase in cell fitness, which we denote as the 'resistance continuum'. This cellular adaptation involves a stepwise assembly of gene expression programmes and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that epithelial-to-mesenchymal transition or stemness programmes-often considered a proxy for phenotypic plasticity-enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify the acquisition of metabolic dependencies, exposing vulnerabilities that can potentially be exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell-state transitions.


Subject(s)
Adaptation, Physiological , Cell Plasticity , Drug Resistance, Neoplasm , Neoplasms , Female , Humans , Mice , Adaptation, Physiological/drug effects , Adaptation, Physiological/genetics , Cell Line, Tumor , Cell Plasticity/drug effects , Cell Plasticity/genetics , Cellular Reprogramming/drug effects , Cellular Reprogramming/genetics , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Epigenesis, Genetic , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Phenotype
17.
Int J Mol Sci ; 25(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38892281

ABSTRACT

Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1ß, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1ß, 6, 8 (IL-1ß, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.


Subject(s)
Cytokines , Disease Models, Animal , Gastrointestinal Microbiome , Persian Gulf Syndrome , Animals , Persian Gulf Syndrome/immunology , Persian Gulf Syndrome/microbiology , Humans , Mice , Cytokines/metabolism , Fecal Microbiota Transplantation
18.
Cureus ; 16(5): e59856, 2024 May.
Article in English | MEDLINE | ID: mdl-38854271

ABSTRACT

Background Cervical cancer ranks among the top five cancers in India, with human papillomavirus (HPV) types 16 and 18 causing up to 70% of related lesions. HPV infection, acquired through various routes, poses risks for both men and women, especially in the age group of 16 to 25 years. Effective prevention is possible through HPV vaccination, with Cervarix and Gardasil approved for use in India. Despite its proven efficacy, HPV vaccine use remains minimal. This study aims to evaluate awareness, willingness, and barriers among female healthcare students while assessing the impact of a health education program on their knowledge and attitude. Methods The present study is an educational interventional study conducted on 489 female students in the healthcare sector in the age group of 19-25 years. Two questionnaires (pre-lecture and post-lecture) were used. After the pre-lecture questionnaire, a session on cervical cancer and vaccine education was delivered by the subject expert. Afterward, the post-lecture questionnaire was given and the impact of session was analyzed using various statistical tools. Result A total of 489 students across MBBS (Bachelor of Medicine, Bachelor of Surgery), BAMS (Bachelor of Ayurvedic Medicine and Surgery), BHMS (Bachelor of Homoeopathic Medicine and Surgery), paramedical, and nursing courses participated in the study. Prior to the lecture, knowledge regarding cervical cancer and vaccines was generally low across subgroups, witnessing improvements ranging from 60% to 100% in various questionnaire sections post-education. Understanding of the importance of a Pap smear (Papanicolaou test) increased significantly from 21% to 79% after the educational session. The most preferred measure to boost coverage was the inclusion of the HPV vaccine in the National Immunization Schedule, with lack of awareness identified as the most significant barrier. Conclusion An educational session not only enhances knowledge but also boosts willingness for cervical cancer vaccination. Inclusion of the vaccine in the National Immunization Schedule not only increases acceptability but also indirectly raises awareness.

19.
ACS Org Inorg Au ; 4(3): 319-328, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38855338

ABSTRACT

As the SIRTi analogue series (HL1-HL6) show potent antitumor activity in vitro, we synthesized their corresponding zinc(II) complexes (ZnL1-ZnL6) and investigated their potential as anticancer agents. The Zn(II) complexes showed substantially greater cytotoxicity than HL1-HL6 alone in several cancer cell-types. Notably, distinct structure-activity relationships confirmed the significance of tert-butyl (ZnL2) pharmacophore inclusion in their activity. ZnL2 complexes were found to transmetalate with copper ions inside cells, causing the formation of redox-active copper complexes that induced reactive oxygen species (ROS) production, mitochondrial membrane depolarization, ATP decay, and cell death. This is the first study to exhibit Zn(II) complexes that mediate their activity via transmetalation with copper ions to undergo paraptosis cell death pathway. To further confirm if the SIRT1/2 inhibitory property of SIRTi analogues is conserved, a docking simulation study is performed. The binding affinity and specific interactions of the Cu(II) complex obtained after transmetalation with ZnL2 were found to be higher for SIRT2 (K i = 0.06 µM) compared to SIRT1 (K i = 0.25 µM). Thus, the concurrent regulation of several biological targets using a single drug has been shown to have synergistic therapeutic effects, which are crucial for the effective treatment of cancer.

20.
Agric Food Secur ; 13(1)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38855478

ABSTRACT

Background: Food insecurity and hunger are global concerns further exacerbated by the unprecedented COVID-19 pandemic. There is a need to understand the depth of this impact, especially among smallholder farmers, and recognize specific coping strategies that offered resilience to inform preparedness in future. The present cross-sectional study assessed the impact of the second wave of COVID-19 pandemic on different dimensions of food security among smallholder farmers of Ho indigenous community of Jharkhand, India. It also explored potential resilient attributes of their food systems. Results: Most of the respondents (67.2%) reported reduced food consumption at the household (HH) level. Majority faced difficulty in accessing food from different food sources; however, easier access to government food security programmes was highlighted. Around 40% reported change in their ability to purchase farming inputs. Market vendors reported disruptions in food procurement owing to travel restrictions; however, no change was reported for home-produced foods in agricultural lands/kitchen gardens. Prices of indigenous foods produced locally decreased/remained same; however, for cereals, pulses, and other HH staples, prices increased during second wave. Difficulty in accessing wild food environment (OR: 1.7, CI 0.40, 7.75), change in food prices (OR: 19.9, CI 5.25, 76.02), decrease in HH income (OR: 9.2, CI 2.99, 28.60) were found to be significantly associated with reduction in HH food consumption (p < 0.01). The coping strategies adopted by the community included sale of cultivated and wild produce in local weekly markets to ensure additional income. Conclusions: The findings highlight the need to reinforce the traditional ecological knowledge of the Ho community and focus on practices around their food systems, engrained into their socio-cultural ecosystems that may offer resilience against future stresses. In addition, the need of systemic support to ensure the social and economic well-being of the community needs to be prioritized.

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