Tag: nevin manimala

Eur J Public Health. 2026 Mar 14;36(2):ckag029. doi: 10.1093/eurpub/ckag029.

ABSTRACT

With increasing life expectancy, multimorbidity represents a growing global challenge, affecting quality of life. We analyzed electronic health records of individuals aged 45-74 from Catalonia, Spain (2007-2021), who were healthy at the end of 2007. We use sequence and cluster analysis to describe and categorize monthly disease accumulation patterns, from healthy to one or multiple conditions or death, involving four disease groups with the highest global morbidity and mortality burdens. We further investigate the association between identified clusters and sociodemographic factors and the association of cluster membership with healthcare utilization. Approximately 36% of individuals remained healthy throughout the study, while the remainder transitioned to single or multiple morbidity and/or died. A higher number of conditions in a given month increased transition probability, with metabolic and hypertensive conditions being the most common entry points. We identified nine disease accumulation trajectories linked to sociodemographic characteristics: Women were more likely to be in clusters involving neurodegenerative conditions and men in those involving cardiovascular and cancer conditions. Higher-income individuals were more likely to be in lower morbidity clusters, except the cancer multimorbidity cluster. Healthcare utilization was elevated in all clusters relative to the healthy group, with notably higher emergency use in cardiovascular clusters and more hospital admissions in cancer-related clusters. The study shows that disease accumulation follows identifiable patterns linked to sociodemographic factors and underscores the propagative nature of multimorbidity. Further, healthcare utilization is shaped more by condition type than by the number, highlighting the need for targeted health services.

PMID:41847870 | DOI:10.1093/eurpub/ckag029

Eur J Public Health. 2026 Mar 14;36(2):ckag028. doi: 10.1093/eurpub/ckag028.

ABSTRACT

Vaccination is a modifiable behaviour resulting from a complex decision-making process influenced by a wide range of factors, including the ‘7Cs’ model (confidence, complacency, constraints, calculation, collective responsibility, compliance, and conspiracy) and the ability to find, understand, evaluate and use vaccine information. This work aimed to analyse the intention to receive a booster dose of the COVID-19 vaccine in Spain in the subsequent rollout of the COVID-19 vaccination campaign and how it was influenced by COVID-19 vaccination health literacy and the ‘7Cs’ determinants of vaccine hesitancy. A descriptive cross-sectional study was conducted in February 2022 using an online survey. The sample comprised 1067 participants aged 18 or older, representative of the Spanish general population. Willingness to receive an additional booster dose of the COVID-19 vaccine was assessed using a single yes/no answer question. Determinants of vaccine readiness were evaluated through seven statements aligned with the 7Cs model, adapted to the COVID-19 context. A multivariable logistic regression showed that vaccination intention was influenced by Confidence (OR = 3.79; 95% CI = 2.58-5.58), Calculation (OR = 0.63; 95% CI = 0.45-0.90), Collective Responsibility (OR = 0.52; 95% CI = 0.32-0.86), Compliance (OR = 2.10; 95% CI = 1.42-3.09), Conspiracy (OR = 0.46; 95% CI = 0.29-0.74), and vaccine related HL (OR = 1.03; 95% CI = 1.02-1.06). Fostering vaccination health literacy, strengthening trust in science and health professionals, fighting misinformation and enhancing collective responsibility are relevant aspects for designing effective vaccination campaigns.

PMID:41847868 | DOI:10.1093/eurpub/ckag028

Toxicol Mech Methods. 2026 Mar 18:1-16. doi: 10.1080/15376516.2026.2645333. Online ahead of print.

ABSTRACT

Arsenic (As) and cadmium (Cd) frequently co-occur in groundwater and target renal proximal tubules. Although each metal can engage ferroptosis pathways, how co-exposure shapes the integrated transcript-protein-lipid ROS axis remains unclear. Human HK-2 cells were exposed for 24 h to commonly used experimental concentrations of As (10 µM), Cd (10 µM), or As + Cd (5 µM + 5 µM). We profiled (i) a focused ferroptosis/oxidative stress gene panel and visualized Z-score heatmaps; (ii) ferroptosis-related proteins (GPX4, SLC7A11, ACSL4, PTGS2, TFR1, ferritin heavy/light chains (FTH/FTL), LC3, Bax/Bcl-2, cleaved caspase-3) by Western blot with densitometric analysis; and (iii) lipid peroxidation using BODIPY 581/591 C11 imaging (oxidized green/reduced red). Statistical analyses were performed using one-way ANOVA followed by Tukey’s post hoc test. These readouts were interpreted alongside measurements of cell viability, ROS, MDA, and metabolomics profiling. Co-exposure produced the most coherent transcriptional shifts across modules regulating iron handling, glutathione-cysteine metabolism, lipid remodeling, CoQ/mitochondrial function, macroautophagy, and NRF2 signaling. Protein analyses corroborated pathway activation: GPX4 and SLC7A11 decreased, whereas ACSL4, PTGS2, and TFR1 increased. FTH/FTL exhibited a downward trend, and LC3-II levels increased, consistent with impaired peroxide detoxification, enhanced polyunsaturated fatty acid (PUFA)-phospholipid acylation, increased iron import, and autophagy engagement. BODIPY C11 imaging revealed the highest oxidized fraction in the As + Cd group, indicating a maximal lipid-peroxide burden. As and Cd act cooperatively to (1) weaken the GPX4-xCT (cystine/glutamate antiporter; SLC7A11) antioxidant axis, (2) increase iron availability and iron-handling stress, and (3) remodel membrane PUFA pools, collectively tipping renal epithelial cells toward ferroptosis. These multi-layer signatures nominate ferroptosis inhibition and iron handling as potential therapeutic targets for mixed-metal nephrotoxicity.

PMID:41847867 | DOI:10.1080/15376516.2026.2645333

Acta Odontol Scand. 2026 Mar 18;85:116-124. doi: 10.2340/aos.v85.45574.

ABSTRACT

OBJECTIVE: This study aimed to investigate the following: (1) the preferences of public dentists for procedures and materials in carious or non-carious pulp exposure of permanent teeth; (2) how factors such as clinical experience, scientific literature reading, and material availability affect their choices; (3) the self-assessed risk of root canal treatment after pulp capping.

MATERIALS AND METHODS: An online questionnaire consisting of 20 multiple choice and open-ended questions was e-mailed to Norwegian public dental clinics. It assessed dentists’ material preferences for direct pulp capping for carious or non-carious exposures, alongside factors such as years since graduation, scientific literature engagement, availability of materials, and clinical scenario choices. Respondents were also asked to estimate and reason long-term outcomes of their chosen materials. Standardized case descriptions ensured shared clinical understanding. Data were statistically analyzed and p-values ≤ 0.05 were considered statistically significant.

RESULTS: A total of 218 (23.9%) dentists responded. Direct pulp capping was preferred by 65% of respondents, with chemically curing materials – primarily calcium hydroxide – being most used. Chi-square analyses showed that dentists with fewer years of experience and those who had read scientific literature were more likely to prefer calcium silicate materials; however, these variables were not statistically significant predictors in the logistic regression models. Material availability was the strongest predictor of preference, with significantly increased odds of selecting calcium silicates or light-curing materials when available. ‘Satisfied with clinical results for the chosen material’ was the most frequently reported reason for material selection.

CONCLUSION: Most respondents in this study preferred calcium hydroxide for direct pulp capping in permanent teeth with closed apices, despite the superior clinical outcomes of hydraulic calcium silicates. Material availability in the clinic was the primary factor influencing dentists’ choices, surpassing clinical experience and scientific literature engagement.

PMID:41847838 | DOI:10.2340/aos.v85.45574

Stat Methods Med Res. 2026 Mar 18:9622802261418211. doi: 10.1177/09622802261418211. Online ahead of print.

ABSTRACT

In interventional health studies, causal mediation analysis can be employed to investigate mechanisms through which the intervention affects the targeted health outcome. Identifying direct and indirect effects from empirical data become complicated, however, when a confounder of the mediator-outcome association is itself affected by the treatment. Here, we investigate identification of mediational effects under such post-treatment confounding in a setting with a longitudinal mediator, time-to-event outcome and an ordinal treatment-dependent confounder. If the treatment affects the treatment-dependent confounder only in one direction (monotonicity), we show that the mediational effects are identified up to stratum-specific sensitivity parameters and derive their empirical non-parametric expressions. The feasibility of the monotonicity assumption can be assessed using empirical data, based on restrictions on the marginal distributions of counterfactuals of the treatment-dependent confounder. In an empirical analysis, we use data from the Finnish Diabetes Prevention Study to assess the extent to which the effect of a lifestyle intervention on avoiding type 2 diabetes is mediated through weight reduction in a high-risk population, with other health-related changes acting as treatment-dependent confounders. We avoid pitfalls related to post-treatment conditioning by treating the mediator as a functional entity and defining the time-to-event outcome as a restricted disease-free time.

PMID:41847826 | DOI:10.1177/09622802261418211

Vestn Oftalmol. 2026;142(1):108-111. doi: 10.17116/oftalma2026142011108.

ABSTRACT

Glaucoma remains one of the leading causes of irreversible vision loss, making it one of the most pressing problems in modern public health.

PURPOSE: This study aimed to identify trends in glaucoma morbidity among adults, adolescents, and children in the Republic of Uzbekistan based on a comprehensive analysis of its prevalence.

MATERIAL AND METHODS: The study used statistical data from the Republican Medical Information Center of the Ministry of Health of the Republic of Uzbekistan for the period 2016-2022. Changes in glaucoma morbidity in 2017-2022 years were analyzed using statistical methods to identify trends and patterns.

RESULTS: The analysis of changes in glaucoma prevalence demonstrated increases in 2016, 2018, and 2021, indicating the potential influence of factors affecting the conditions of glaucoma diagnosis and treatment.

CONCLUSION: The findings confirm the growing relevance of glaucoma as a serious medical and social problem, particularly among the adult population. The results may serve as a basis for developing effective preventive measures and optimizing treatment strategies to reduce the rate of irreversible vision loss.

PMID:41847815 | DOI:10.17116/oftalma2026142011108

Vestn Oftalmol. 2026;142(1):79-86. doi: 10.17116/oftalma202614201179.

ABSTRACT

PURPOSE: The secondary objectives of the study were to describe the sociodemographic and clinical characteristics of patients with inherited retinal dystrophy (IRD) phenotypes, including Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), to characterize the diagnostic and treatment pathways of patients with confirmed biallelic mutations in the RPE65 and/or RLBP1 genes, and to estimate the prevalence of RPE65-associated inherited retinopathy and RLBP1-associated pathology in Russia.

MATERIAL AND METHODS: This noninterventional cohort study was conducted using retrospective data collected from patients with LCA and RP phenotypes in Russia and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes. The registry was formed between July 20, 2022 and March 3, 2025. Eligible participants were entered into the database, followed by a two-stage genetic diagnostic algorithm to confirm biallelic mutations in the RPE65 or RLBP1 genes. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study included 2425 patients from 83 regions of the Russian Federation diagnosed with IRDs. The majority of patients were from Moscow, the Moscow Region, the Republic of Dagestan, the Republic of Tatarstan, Saint Petersburg, and the Republic of Bashkortostan. The mean age was 23.22±16.74 years, pediatric patients accounted for 51.34% of analyzed cases. Females and males comprised 47.01% and 52.99% of the cohort, respectively. In patients with confirmed biallelic mutations in the RPE65 gene, disease onset was characterized by nyctalopia (47.5%), nystagmus (40%), pigment redistribution (40%), non-recordable/extinguished electroretinogram (45.0%), and prolonged dark adaptation (35.0%). Mean best-corrected visual acuity was reduced (OD: 0.14±0.12; OS: 0.15±0.13), while central retinal thickness in the foveal region remained relatively preserved (OD: 178.70±38.43 µm; OS: 179.17±35.97 µm).

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia (REGINA)” allowed evaluation of a representative IRD cohort, providing a detailed description of key clinical, social, and demographic characteristics.

PMID:41847811 | DOI:10.17116/oftalma202614201179

Vestn Oftalmol. 2026;142(1):70-78. doi: 10.17116/oftalma202614201170.

ABSTRACT

PURPOSE: The primary objective of the study was to investigate and describe the molecular genetic characteristics of patients with inherited retinal dystrophies (IRDs) presenting with phenotypes of Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP), taking into account clinical polymorphism.

MATERIAL AND METHODS: This noninterventional cohort study was conducted in Russia by collecting retrospective data from patients with LCA and RP phenotypes and annual prospective follow-up of patients with IRDs caused by biallelic mutations in the RPE65 or RLBP1 genes, entered into the registry between July 20, 2022 and March 3, 2025. Eligible participants were entered into the IRD database, followed by a two-stage genetic diagnostic algorithm to confirm the presence of biallelic mutations in RPE65 or RLBP1. The data were entered into standardized electronic case report forms, verified, and analyzed using descriptive statistical methods.

RESULTS: The study cohort included 2425 patients with IRDs from 83 regions of the Russian Federation. The mean age was 23.22±16.74 years, with predominance of pediatric patients (51.34%) and males (52.99%).

Genetic testing was performed in two stages. At the first stage, mutations in RPE65 and/or RLBP1 were identified in 84 (3.52%) of 2388 examined patients. The second stage involving direct Sanger sequencing was conducted in 48 (2.01%) patients, it confirmed biallelic mutations in RPE65 in 1.68% and in RLBP1 in 0.04% of cases. In one case, mutations in both genes were verified. Among RPE65 variants, 61 mutations were identified, including frequent pathogenic variants (c.304G>T, c.272G>A, c.370C>T); seven variants were detected in the RLBP1 gene.

The frequency of biallelic RPE65 mutations in the subgroup with LCA/RP phenotype was 1.68%, and 1.65% in the overall IRD cohort, which is consistent with published data from European populations.

CONCLUSION: The study “Registry of patients with inherited retinal dystrophies caused by confirmed biallelic mutations in the RPE65 and RLBP1 genes in Russia” allowed characterization of the key molecular genetic features of a representative sample of patients with IRDs.

PMID:41847810 | DOI:10.17116/oftalma202614201170

Vestn Oftalmol. 2026;142(1):60-69. doi: 10.17116/oftalma202614201160.

ABSTRACT

PURPOSE: This study aimed to investigate the morphological features of the lamina cribrosa (LC) of the scleral in terms of their potential role in optic nerve (ON) axonal injury.

MATERIAL AND METHODS: Longitudinal sections of the prelaminar, laminar, and postlaminar portions of the ON from human corneal donors were examined. Sections were stained with Masson’s trichrome and analyzed using the Bioscan AT+ software. Neurofilament (NF) expression was assessed immunohistochemically using the Neurofilament NE-14 antibody and quantified with ImageJ 1.54i. Statistical analysis included Pearson and Spearman correlation coefficients, as well as the Kruskal-Wallis, Mann-Whitney, and Kendall’s tau tests.

RESULTS: The ratio of connective tissue to neural components in the LC varied and correlated with age (χ²=21.09, p=0.0018). Based on these differences, three LC patterns were identified: mixed, elastic, and collagenous. The mixed LC pattern was most prevalent across all age groups; the elastic pattern predominated in younger individuals (<44 years); the collagenous pattern was most common in individuals older than 60 years. NF expression was lowest in the mixed type LC, increased significantly in the elastic type LC, and was highest in the >60-year age group with the collagenous type LC.

CONCLUSION: Remodelling of the LC of the sclera characterized by a predominance of collagenous tissue, primarily perivascularly, and accompanied by deformation of the anterior LC surface in individuals older than 60 years, together with a tendency toward increased deviation of ON axons passing through the LC, should be considered potential risk factors for ON axonal injury. The observed variability in the NF cytoskeleton, which preceded changes in axonal transport, may be used as an early marker of retinal ganglion cell damage.

PMID:41847809 | DOI:10.17116/oftalma202614201160

Vestn Oftalmol. 2026;142(1):14-20. doi: 10.17116/oftalma202614201114.

ABSTRACT

INTRODUCTION: The ability of the crystalline lens to change its shape is a key component of accommodation. As part of the lenticular theory of presbyopia, involutional changes in the lens substance itself are considered to be of primary importance. At the same time, the role of the capsule, which essentially serves as a structural, shape-modifying “framework” for the lens substance, remains insufficiently studied. Accordingly, one approach to clarification of the pathogenesis of presbyopia may involve investigating the relationship between potential changes in lens shape during accommodation and the biomechanical properties of its capsule.

PURPOSE: This study aimed to assess the potential relationship between accommodative stimulus-induced changes in the curvature of the anterior lens surface and the biomechanical parameters of the anterior capsule based on sequential clinical and experimental analysis.

MATERIAL AND METHODS: The study was conducted in a group of 11 patients (11 eyes, i.e., clinical observations) of presbyopic age scheduled for and undergoing standard phacoemulsification with intraocular lens implantation for uncomplicated cataract. Prior to surgery, the radius of curvature of the anterior lens surface was measured at baseline and under accommodative stimulus using the CASIA2 device (Tomey, Japan). Anterior lens capsule specimens with a diameter of 4.0-5.5 mm were obtained during surgery after continuous curvilinear capsulorhexis. The elastic modulus (Young’s modulus) of the specimens was determined using atomic force microscopy.

RESULTS: Correlation analysis involved the use of an integral parameter – the magnitude of change in the radius of curvature of the anterior lens surface induced by accommodative stimulus. A pronounced moderate positive correlation was identified between changes in the radius of curvature of the anterior lens surface and the elastic moduli of the outer and inner surfaces of the anterior capsule (r=0.560 and r=0.603, respectively). However, this relationship was statistically significant only for the inner surface of the capsule but not for the outer surface (p=0.050 and p=0.073, respectively).

CONCLUSION: This is the first study investigating the potential relationship between changes in the curvature of the anterior lens surface and the biomechanical properties of the anterior capsule using the same study object, which enabled sequential clinical (morphometric) and experimental (biomechanical) analyses. Based on the obtained results, age-related changes in the biomechanical properties of the lens capsule may be considered one of the factors within the lenticular theory of presbyopia development.

PMID:41847803 | DOI:10.17116/oftalma202614201114