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District hospitals are integral part of India's public healthcare delivery system, yet national-level assessment of their efficiency is lacking. This research assesses the technical efficiency of district hospitals in India and identifies key determinants influencing their performance. Data envelopment analysis was utilized to measure the efficiency scores of district hospitals. The estimates of input and output variables from district hospitals were sourced from the primary data comprising 27 district hospitals across nine Indian states. Input variables included human resources for health, physical medical infrastructure, and the economic value of all other resources consumed to deliver health services, whereas the output variables comprised hospital workload indicators such as number of hospitalizations, surgeries, and outpatient episodes. Tobit regression investigated the factors influencing hospital efficiency. 85.2% of the district hospitals ( n = 23) under the variable returns to scale model and 74.1% of the hospitals ( n = 20) under the constant returns to scale model had efficiency scores above the threshold of 0.9, suggesting high operational efficiency. Mean technical efficiency (TE), pure technical efficiency (PTE), and scale efficiency scores were 0.88, 0.94, and 0.93, respectively. The hospitals serving larger proportions of very young or elderly populations exhibited lower TE (β = -0.017). The hospitals located in tier 2 (β = 0.653) and tier 3 cities (β = 0.600) exhibited higher PTE than those in tier 1 cities. Most district hospitals are performing efficiently; thus, increasing output would require a higher budget. Progress toward universal health coverage necessitates either enhanced inputs or more district hospitals.
V2O5 and Fe2O3 doped phosphotellurite glasses were synthesized and investigated experimentally for density, structure, temperature and frequency dependent dielectric properties, ac conductivity and, radiation shielding parameters were computed. Electric modulus and impedance spectra exhibited a non-Debye type relaxation behavior. Conductivity master curves demonstrated that the dielectric relaxation and conductivity depend on composition and unaffected by temperature. By fitting measured conductivity to Jonscher's universal power law, conductivity (ac and dc) and frequency exponent were extracted. Conductivity and activation energy passed through maximum and minimum respectively for 0.2 mol fractions of Fe2O3 indicating occurrence of mixed transition effect. Overall electric studies suggest that the present glasses are promising candidates for energy storage devices and solid-state electrolytes. For the energy range 0.015-15 MeV, various gamma and neutron shielding parameters were computed using the Phy-X software. They were analyzed and compared with literature and found that these glasses are most useful for radiation shielding.
A marine hydrocarbonoclastic actinobacterium Kocuria flava IOS11 was isolated from 3500 m deep-sea water of the Indian Ocean. The isolate efficiently degraded phenanthrene (250 mg/L) achieving 82 and 98% of degradation at 0.1 MPa and 20 MPa, respectively within a period of 5 days. Whole genome, transcriptomee and metabolomic analysis elucidated its phenanthrene biodegradation efficiency under in situ deep-sea conditions. The genome sequence comprises 3.47 Mb distributed across 88 scaffolds with a high GC content of 74.30%. The genome analysis encoded 3126 genes including 3052 protein coding sequences with functional annotation identifying a broad array of genes associated with PAHs degradation, environmental stress adaptation, biosurfactant and siderophore synthesis. Transcriptome profiling under 0.1 and 20 MPa conditions with phenanthrene as a sole carbon source revealed enhanced expression of hydrocarbon degrading genes, transporters, biosurfactant associated enzymes and stress responsive genes including integrases, DNA repair protein Rad, alanine ligase, heat and cold shock proteins under high pressure conditions underscoring the deep-sea adaptation capabilities of the strain. The degradation pathway of phenanthrene was proposed through integrated genome, transcriptome and metabolomic analysis. These studies provided K. flava IOS11 as a metabolically versatile and pressure adapted bacterium with promising potential for bioremediation application in extreme marine environment.
High-quality artificial intelligence (AI) models in endodontics require access to diverse, well-annotated datasets. This review introduces federated learning (FL) as a privacy-preserving framework for collaborative AI in endodontics. In this narrative review, a comprehensive literature search was conducted across databases, encompassing studies published up to April 2026. The search strategy was intentionally broad to facilitate a thorough exploration of the evolution of the relevant concepts. However, to ensure consistency in comprehension and analysis, the review was limited to publications in English. Studies describing the fundamentals and applications of FL were reviewed and comparatively analysed. The narrative review served as the framework for outlining implementation pathways, challenges, and research priorities for its application to diagnostic and decision-support tasks. Traditional centralised training methods face legal and ethical challenges due to data protection regulations. FL allows institutions to retain local patient data while contributing model updates to a central server or decentralised network, thus providing a viable alternative. The article explores FL principles, privacy and security mechanisms, architectures, technical challenges, and adversarial risks. Regulatory and ethical considerations hinge on a mix of advanced technical measures and robust organisational practices. A proposed roadmap for implementing FL includes pilot studies, standardised data processes, clinical validation, and regulatory engagement. FL promises to enhance AI development in endodontics while safeguarding patient privacy, with potential benefits in diagnostics and personalised care. FL could advance AI integration in endodontics, prioritising the protection of patient privacy. This initiative holds the potential to improve diagnostic processes and facilitate personalised treatment approaches. FL enables the development of multicentre AI models without sharing patient data. By leveraging diverse clinical datasets, this approach may improve the accuracy and generalisability of AI systems for endodontic diagnosis, treatment planning, and outcome prediction while preserving patient privacy.
Leptospirosis, a bacterial zoonosis predominantly reported post floods, has recently been increasingly reported during the nonrainy seasons. We studied 159 leptospirosis cases reported between January and May and identified environmental and behavioral factors. Most cases resided in tenement buildings (52.8%) with pooling of water around community taps, use of common bathrooms along with the presence of rodents, and solid waste dumps. Regardless of the season, water plays a crucial role in the transmission of leptospirosis. Rodent control measures need to be strengthened along with the management of water collection and solid waste management. Clinicians must maintain a high index of suspicion for leptospirosis year-round.
Kalyanaka Ghrita (KG) is a classical Ayurvedic polyherbal formulation traditionally indicated for disorders of memory, intellect, and mental well-being. Ayurveda emphasizes individualized therapeutic decision-making, which the N-of-1 trial design aligns with conceptually and methodologically, enabling systematic evaluation of traditional formulations at the single-patient level, where inter-individual variability is central. To assess the efficacy and safety of Kalyanaka Ghrita in a patient diagnosed with Mild Cognitive Impairment (MCI) using an N-of-1 trial design. A quasi-randomized N-of-1 trial was conducted to evaluate the effects of KG in a patient with MCI. The study comprised six alternating treatment and no-treatment periods of two months each, spanning a total of 14 months. Cognitive outcomes were assessed using the Hindi Mental State Examination (HMSE) and the Clinical Dementia Rating (CDR) scales. Functional abilities were measured with the Instrumental Activities of Daily Living (IADL) scale, and affective status was evaluated using the Geriatric Depression Scale (GDS)- short form. Bayesian modeling estimated posterior probabilities and 95% highest posterior density intervals (HPDI) for treatment effects. KG administration improved overall cognitive abilities, as indicated by global HMSE scores (posterior probability >97%, 95% HPDI excluding zero), with the most substantial gains in orientation (posterior probability >98%) and recall (posterior probability >93%) domains. Reduction in CDR-Sum of Boxes scores indicated strong improvement (posterior probability >98%; 95% HPDI excluded zero). Benefits were consistent in orientation and community affairs, with moderate effects on memory and judgment/problem-solving. Functional outcomes assessed using IADLs showed a probable benefit (posterior probability >80%, HPDI overlapping zero). Depressive symptoms, as measured by the GDS, decreased markedly (posterior probability = 100%; 95% HPDI -2.23 to -0.80). All safety lab parameters remained within physiological limits, confirming good tolerability of KG. KG produced measurable improvements across cognitive, functional, and affective domains in a patient with MCI, suggesting a potential role in the management of early cognitive decline. The formulation was well tolerated. The study also demonstrates the feasibility of applying an N-of-1 trial within Ayurveda. Despite limitations such as the single-patient, quasi-randomized, open-label design and absence of biomarker testing, the findings offer preliminary support for both the therapeutic potential of KG in MCI and the methodological value of N-of-1 trials in Ayurvedic research.
Bone marrow-derived mesenchymal stromal cells (BMSCs) have been shown to enhance regeneration and repair, even in challenging neurological conditions such as spinal cord injury (SCI). However, their clinical application for SCI remains inconsistent, likely due to variability in therapeutic outcomes. In our laboratory experiments, we observed similar inconsistencies, including instances where the presence of BMSCs compromised the survival of co-cultured neurons subjected to oxidative stress in vitro. The present study was carried out to find answers for such paradoxical effects caused by BMSCs using an in vitro model involving primary cultured neurons and BMSCs. Both neurons and BMSCs were found to upregulate brain-derived neurotrophic factor (BDNF) production under oxidative stress. To simulate BMSC-mediated release, we introduced exogenous mature BDNF (mBDNF) to stressed neurons in cultures, which unexpectedly led to apoptosis. Observations suggest the possibility of mBDNF-p75 neurotrophin receptor (p75NTR) mediated cell death signaling. Notably, administration of a p75NTR inhibitor (LM11A-31, a small molecule) partially alleviated these detrimental effects. Given the growing interest in BMSC-based therapies, these findings underscore concerns regarding the variability of their effects and the potential for unintended neurotoxicity. Addressing these inconsistencies through further studies will be critical to ensuring the safety and efficacy of BMSC applications in clinical settings. In this regard, concomitant inhibition of p75NTR using small molecules such as LM11A-31 may have potential to avoid contradictory effects of BMSC transplantations caused by unpredictable release of excess BDNF in the transplanted site.
Following the 1989 universal infant vaccination mandate, Saudi Arabia achieved significant reductions in Hepatitis B Virus (HBV) prevalence. The spatiotemporal dynamics of HBV notifications were performed to identify the "unfinished success" of the national elimination program. We conducted a retrospective analysis of national HBV notification data (2019-2023). Gini coefficients measured inequality while Pareto analysis identified high-concentration foci. Vaccination program impact (VPI) was estimated by comparing pediatric (0-14 years) to adult notification rates (NR). Population attributable fraction (PAF) and VPI modeled the leverage of targeted versus universal screening strategies. A 75.6-fold higher NR in adults (30.24/100,000) than children (0.40/100,000; P < 0.001) was observed, with a Gini of 0.43 indicating high age-based inequality. PAF showed 98.2% of the national burden is concentrated in adults (15+ years). VPI was 98.7% [95% CI: 98.1%-99.1%], preventing an estimated 2,507 pediatric cases in 2023. The national NR exhibited a V-shaped trajectory: a 50.7% decline during the COVID-19 pandemic followed by a complete rebound by 2023, identifying the decline as a surveillance artifact. Saudi males had a 1.5-fold higher NR than females (58.45 vs. 37.93/100,000; NR Ratio = 1.54; P < 0.001). Geographically, Pareto analysis confirmed 78.5% of the burden concentrated in four regions, with Jazan as the primary hotspot (NR: 72.53). While infant vaccination has reached diminishing returns against the adult reservoir, we propose pivoting to a "Precision Public Health" approach, prioritizing targeted screening and linkage-to-care for Saudi adult males within identified geographic hotspots.
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Forensic identification, pediatric dentistry, and medico-legal investigations all often utilize dental age estimation. Demirjian and Willems methods are frequently used when estimating dental maturity; however, their accuracy varies across different groups, pointing to the need for population specific validation. Aim of the current study was to compare and assess the reliability of the Demirjian and Willems for estimating dental age in the children from the Indian state of Chhattisgarh. A retrospective cross-sectional study was conducted using 142 orthopantomograms of children aged 10-16 years. Dental age was estimated using Demirjian and Willems methods based on the developmental stages of the seven left mandibular permanent teeth. The accuracy was assessed using mean error (ME) and mean absolute error (MAE). Pearson correlation and paired t-tests were used to evaluate statistical analysis. The Demirjian method showed a tendency to overestimate age in younger individuals and underestimate age in older age groups. The Willems method demonstrated comparatively smaller deviations from chronological age and often yielded better and more reliable age estimates. Both methods show positive correlation between chronological age and dental age. The Willems method showed higher accuracy than the Demirjian method in this Chhattisgarhi population for dental age estimation.
Tibetans have lived in India as refugees since 1959, and addressing their health needs is a moral responsibility. Community healthcare for refugees often neglects oral health, giving it lower priority than other health issues, particularly among underprivileged groups. Age is a significant sociodemographic factor, as oral health tends to deteriorate in the elderly due to tooth loss and periodontal problems. Due to insufficient comprehensive data, a need was felt for conducting this study in Shimla city. To assess oral health status and treatment needs among elderly Tibetan refugees in Shimla city and establish valid baseline data. A cross-sectional study was conducted (May-October 2022) among the entire elderly Tibetan population (≥60 years) in Shimla. Oral health status and treatment needs were recorded using the World Health Organization Oral Health Assessment Form (2013). Data were analyzed using SPSS version 26, with P < 0.05 considered statistically significant. Among the study population, 49% were males and 51% were females, mostly in the 60-69 age group. Dental caries prevalence was 78.4%, and the mean DMFT score was 17.69, significantly higher among males compared to females. Periodontal disease was observed in 63.7% of participants, with a higher prevalence in the 60-69 age group. The study revealed poor oral health among the elderly Tibetan refugee population. Treatment needs increased steadily with age, highlighting the need for targeted oral health care services for this vulnerable population.
Cardiac fibrosis is one of the main causes of mortality from cardiovascular disorders and may result in heart failure, irregular heartbeats, and sudden cardiac death. Multiple complex mechanisms involved in cardiac fibrosis are beyond the scope of current treatments. Inflammasomes are significant inflammatory modulators. Inflammasome impairment may exacerbate heart failure. The most specific inflammasome associated with inflammatory and cardiovascular disorders is Nucleotide-binding oligomerisation domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3). Pathogen-associated molecular patterns and damage-associated patterns are recognised by the intracellular sensor NLRP3, which causes the NLRP3 inflammasome to assemble and become active. Thus, a greater awareness of the pathological function of the inflammasome in heart fibrosis may lead to new approaches to the disease's early detection and management. Understanding the inflammasome's regulatory functions in fibrosis of the heart in its entire form has been made possible by recent research on the subject. The most recent studies on the roles of the NLRP3 inflammasome in different cardiac conditions are included in this review. According to recent research, the NLRP3 inflammasome promotes a number of inflammatory reactions and is linked to myofibroblast development, mitochondrial modulation, and pyroptosis in cardiac fibrosis. These discoveries provide light on the critical function of the NLRP3 inflammasome in the aetiology of heart fibrosis, which may help establish novel paths for therapy and prevention.
Pediatric dermatoses presenting as follicular papules are common entities encountered in clinical practice. These are a heterogeneous group of disorders of infectious or noninfectious origin that commonly present as regularly spaced, small papules with or without perifollicular inflammation. Inflammatory causes include follicular eczema, pityriasis rubra pilaris, lichen nitidus, follicular seborrheic dermatitis, keratosis pilaris and its variants, keratosis circumscripta, follicular psoriasis, lichen spinulosus, follicular lichen planus, follicular mucinosis, perforating folliculitis, follicular porokeratosis, and follicular dermographism. These conditions may arise due to filaggrin mutations, keratinization defects, autoimmunity, or microbial triggers. Nutritional causes include phrynoderma and scurvy, while connective tissue diseases such as dermatomyositis and chronic cutaneous lupus erythematosus are autoimmune. Additional categories include infectious, genetic, hormonal, environmental, frictional, malignant, nevus-related, iatrogenic, and idiopathic entities. An early and accurate diagnosis is essential for proper management and reducing disease-associated apprehension in children and/or their parents. This review attempts to describe the role of history taking and clinical examination, including morphology, location, pattern of distribution, and associated features, while dealing with a child with follicular-based papules. In addition, it delineates the role of dermoscopy and pathological examination in reaching a correct diagnosis. Furthermore, it describes the available treatment options and disease course of various follicle-based dermatoses.
In the quest for new antidiabetic agents, a library of twenty-three 1,4-dihydropyridine-pyrazole derivatives was synthesized via an efficient green multicomponent Hantzsch reaction. The compounds were screened in vitro for GLUT4 translocation stimulatory activity in L6-GLUT4myc myotubes, and subsequently evaluated in vivo for anti-hyperglycemic effects in a streptozotocin-induced diabetic rat model. Several compounds, particularly 6c, 6 h, 6j, 6 l, and 6 m, significantly enhanced GLUT4 translocation to cell surface in L6-GLUT4myc myotubes, suggesting improved glucose uptake potential. Among them, compound 6c exhibited the highest activity and produced a significant reduction in blood glucose levels (23.9%, p < 0.01) in diabetic rats. The observed biological activity highlights the therapeutic relevance of the 1,4-dihydropyridine-pyrazole scaffold and identifies compound 6c as a promising lead for further structure-activity relationship studies aimed at the development of novel antidiabetic agents.
Insulin, a peptide hormone commonly used in the therapeutic management of diabetes mellitus, is anticipated to aggregate at sites of recurrent injections in diabetic patients. These aggregates are comprised of insoluble insulin fibrils, which can lead to localized inflammatory reactions and impaired insulin uptake. Therefore, it is essential to formulate strategies inhibiting the insulin fibrillation for better therapeutic applications. The phytochemicals, that exhibit anti-fibrillating properties, have shown a promising efficacy in mitigating insulin amyloidosis. Hence, the effects of Mangiferin (Mg), Rosmarinic Acid (RA), and Curcumin Cysteine Complex (CCC) are explored for insulin anti-fibrillating potentials at physiological pH. CCC and RA efficiently inhibit insulin fibrillation in a dose-dependent manner by binding to the aggregation-prone regions of the protein, suggesting a plausible mechanism for their anti-fibrillating potentials. In vivo findings revealed that treatments with the insulin-phytochemical formulations are more therapeutically effective in mitigating diabetic traits in Drosophila than monomeric insulin alone. Among the studied phytochemicals, insulin formulation with CCC showed the most pronounced efficacy in restoring the normal physiology in HSF-induced diabetic flies. Thus, CCC presence in insulin formulation offers a promising strategy to further stabilize the formulations against in vitro and in vivo insulin amyloidosis.
Fungal infections caused by Aspergillus fumigatus pose a serious clinical challenge, particularly in immunocompromised patients, where limited therapeutic options and increasing resistance reduce treatment success. Chitinase B1 is a key enzyme involved in fungal cell wall remodeling and has emerged as an attractive molecular target for antifungal drug discovery. In this study, an integrated computational workflow was employed to identify and evaluate potential inhibitors of A. fumigatus Chitinase B1. A total of 99288 compounds were screened from MTi open screen web server and these structure -based screening resulted in the selection of three promising compounds (124753220, 26746900, and 17439543) based on their highest binding affinity with a docking score between -11.6 to -9.3 kcal/mol within the enzyme active site. Electronic structure analysis of compound 124753220 revealed a high dipole moment and narrow HOMO-LUMO gap, indicating favorable chemical reactivity. Redocking analysis confirmed stable hydrogen bonding and hydrophobic interactions with key catalytic residues. Molecular dynamics simulations conducted over 500 ns demonstrated stable complex formation, as reflected by consistent RMSD score of 1.5-2.0 Å and RMSF below 2.0 Å for all selected profiles. Binding free-energy analysis identified compound 124753220 as the strongest binder (ΔG_total = -78.54 kcal/mol), exhibiting affinity comparable to the reference inhibitor. Principal component analysis and free energy landscape confirmed the stability of the protein-ligand complexes. while QM/MM calculations indicated favorable electronic interactions within the binding pocket. Machine learning-based bioactivity predictions showed comparable potency among all evaluated compounds (pIC₅₀ = 8.225-8.619). Overall, compound 124753220 demonstrated the most favorable binding and stability characteristics, highlighting its potential as a promising antifungal lead for further experimental validation.
The conceptual framework of biased agonism has greatly impacted our understanding of G-protein-coupled receptor (GPCR) signaling, regulatory paradigms, and drug discovery efforts. Here, we present fundamental molecular and structural insights into intrinsic bias encoded at the human and mouse complement anaphylatoxin C5a receptors, namely C5aR1 and C5aR2. We discover that a naturally occurring version of C5a, i.e., C5a-d-Arg, exhibits a robust G-protein-coupling bias at C5aR1 with attenuated β-arrestin (βarr) recruitment, which originates from a distinct conformation of TM7 and helix 8 in the receptor, leading to inefficient GRK recruitment and phosphorylation. We also determine a series of cryo-electron microscopy (cryo-EM) structures of C5aR2, a naturally encoded βarr-biased receptor, which uncover key differences in anaphylatoxin recognition by C5aR2 relative to C5aR1. These structural snapshots also uncover a shallower cytoplasmic pocket in C5aR2 with a hydrophobic interior, which is likely incompatible with efficient G-protein coupling, leading to intrinsic bias. Our findings illuminate the molecular basis of naturally encoded signaling bias at GPCRs, with direct implications for therapeutic design.
Light chain (LC) amyloidosis (AL) is a fatal disorder caused by extracellular aggregation of monoclonal immunoglobulin LCs. While both λ and κ isotypes can be involved, κ-LCs account for only ∼20% of cases, and their aggregation mechanisms remain less understood. Recent evidence suggests that N-glycosylation influences κ-LC aggregation and is strongly linked to AL amyloidosis. To investigate this, we examined patient-derived κ-LCs in both glycosylated and unglycosylated forms. Mass spectrometry confirmed the presence of complex-type N-glycans. Biophysical analyses showed that glycosylation enhances structural compactness, stabilizes the native structure, and promotes cooperative unfolding. Glycosylated κ-LCs also exhibited reduced conformational dynamics. Functionally, N-glycosylation significantly improved LC secretion efficiency and extracellular stability. These findings suggest that N-glycosylation acts as a protective factor against amyloid formation and enhances LC accumulation outside the cell. Overall, our study highlights the multifaceted and context-dependent role of N-glycosylation in modulating κ-LC behavior, with important implications in AL pathogenesis.