K.S. Hegde Medical Academy

The increasing incorporation of multiple sweeteners into processed foods underscores the need to evaluate their combined genotoxicity. Epidemiological studies associate high intake of sweeteners with elevated risks of cardiovascular, cerebrovascular, and metabolic disorders, yet the genetic consequences of their combined consumption remain largely unexplored, highlighting the necessity of assessing their interactive genotoxic risks. This study therefore aimed to investigate the genotoxic and developmental toxicity of the widely used artificial sweeteners, acesulfame potassium (ACE K), aspartame (ASP), and stevia (S), individually and in relevant binary and ternary combinations (ACE K + ASP, ACE K + S, ASP + S, and ACE K + ASP + S) at 10, 30, and 50 mM. Genotoxicity was assessed using the Drosophila SMART assay, complemented by molecular docking and 100-ns dynamic simulations with the developmental regulators Engrailed (En) and Hedgehog (Hh), and toxicity prediction via ProTox-3.0. All sweeteners produced dose-dependent genotoxic effects, with ACE K–containing mixtures showing higher spot frequencies at 10 mM, while ASP + S exhibited stronger genotoxicity at 30 and 50 mM; the triple combination consistently mirrored the 10 mM trend. In silico analyses revealed higher binding affinities of ACE K toward En and Hh, aligning with in vivo observations. Collectively, these findings demonstrate concentration-dependent genotoxic risks associated with sweetener mixtures and indicate that formulations incorporating stevia may offer relatively safer alternatives for food applications.

Myoepitheliomas are rare benign salivary gland tumours, representing less than 1

Summary: Background: Data of Central Nervous System (CNS) demyelinating disorders from India has been published from limited centres. The Indian Multiple Sclerosis And Allied Demyelinating Disorders Registry and Research Network (IMSRN) is a multicentric database for multiple sclerosis and allied demyelinating disorders in the Indian subcontinent. This study aimed to describe the demographic, clinical, laboratory, treatment, and follow-up details of patients in the IMSRN and summarise the distribution of major disease phenotypes in a real-world cohort. Methods: This was a prospective, observational, registry-based analysis of patients with CNS demyelinating disorders enrolled in the IMSRN between 16 August 2021 and 25 October 2025. Data were collected in a predefined case record form at recruitment and periodically every six months on a secure database. We performed descriptive and comparative analyses, including temporal trends, treatment patterns, and longitudinal follow-up. Findings: As of 25th October, 2025, 4976 patients have been recruited including radiologically isolated syndrome (RIS), 15 (0.30%); clinically isolated syndrome (CIS), 200 (4.02%); multiple sclerosis (MS), 2479 (49.82%); neuromyelitis optica spectrum disorder (NMOSD), 793 (15.94%); myelin oligodendrocyte antibody associated disease (MOGAD), 698 (14.03%); acute disseminated encephalomyelitis (ADEM), 76 (1.53%); chronic relapsing inflammatory optic neuritis (CRION), 34 (0.68%); chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), three (0.06%), and others, 562 (11.29%). The mean (SD) age of the entire cohort at enrolment is 34.62 (12.16) years, at disease onset was 29.12 (11.80) years and median (IQR) disease duration at recruitment is 2.79 (0.51–7.22) years; longest for MS. There were 65.33% females and 34.67% males, with a female-to-male ratio of 1.9:1; highest in NMOSD (3.58:1). Most patients are from urban areas and educated. Optic nerve and spinal cord involvement were the dominant areas at first presentation. The median (IQR) number of relapses per patient over follow-up was 2 (1–3) highest in the NMOSD population; dominated by optic nerve and spinal cord symptoms. The median (IQR) EDSS was 2 (1–4.5). Rituximab was the commonest disease modifying therapy (DMT) used. Longitudinal trends reflect improvement in time-to-diagnosis and significant shift in the pattern of DMT use in MS towards oral DMTs and B-cell inhibitors. Interpretation: The paper describes a cohort of patients with MS and allied disorders. The key disease characteristics of the MS population seem similar to those reported in international MS registries. The data adds to the existing literature to ascertain disease patterns, response to treatment, and long-term outcome. Funding: The IMSRN registry is funded by the Indian Council of Medical Research (ICMR) vide Grant number 5/4-5/192/NeuroTF/2019-NCD-1.

Ovarian germ cell tumors (OGCTs) arise from primordial germ cells and are the second most common ovarian neoplasms after surface epithelial tumors. While the majority are benign, approximately 5

The neurodevelopmental, jaw, eye, and digital syndrome shows high clinical variability and is caused by heterozygous FBXW11 missense variants. FBXW11 encodes an F-box protein containing a WD40 domain that forms a seven-bladed β-propeller. FBXW11 is part of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex, which mediates the ubiquitination and proteasomal degradation of numerous substrates, thereby regulating diverse cellular processes and pathways. Here, we report a de novo FBXW11 missense variant, NM_033644.3:c.1100 C > T; p.(Ser367Phe), in an infant with developmental delay and severe skeletal phenotype characterized by multisuture craniosynostosis with turricephaly and postaxial polysyndactyly. We studied the functional consequences of the reported FBXW11 variants p.(Gly229Arg), p.(Arg350Trp), and p.(Glu431Lys), as well as p.(Ser367Phe), all located within the WD40 substrate-binding domain, by ectopic expression of HA-tagged wild-type and variant FBXW11 β-isoforms. Subcellular localization studies revealed FBXW11WT mainly in the nucleus. HA-FBXW11E431K showed either nuclear or nucleo-cytoplasmic distribution, whereas FBXW11G229R and FBXW11S367F were excluded from the nucleus. Using liquid chromatography-tandem mass spectrometry and independent co-immunoprecipitations, we identified variant-specific and shared alterations in FBXW11 interaction networks. Decreased complex formation with the SCF components was observed for FBXW11G229R. Both FBXW11G229R and FBXW11S367F showed reduced binding to the nuclear substrate SUN2. Enriched complex formation of FBXW11G229R and FBXW11S367F with the chaperonin-containing TCP-1 (CCT) subunits suggests that both FBXW11 protein variants are trapped by CCT, potentially delaying or arresting folding of FBXW11’s β-propeller. Together, our data show that FBXW11 missense variants differentially affect binding to specific substrates and/or interaction partners, providing a molecular explanation for the clinical variability.