Cerebrospinal fluid (CSF) dynamics within the optic nerve subarachnoid space (ONSAS) are increasingly recognised as potential factors contributing to the pathogenesis of optic neuropathies, including normal-tension glaucoma (NTG) and idiopathic intracranial hypertension (IIH). In this study, high-resolution T2-weighted magnetic resonance imaging (MRI) data were manually segmented and processed for greyscale analysis and pixel-intensity mapping, enabling anatomically accurate three-dimensional reconstructions of the ONSAS. These reconstructions were imported into OpenFOAM software for computational fluid dynamics (CFD) simulations, incorporating physiologically realistic inlet pressure waveforms, boundary conditions, tissue porosity, and lymphatic drainage characteristics in the near optic nerve head portion of ONSAS, called the distal portion. Solver selection in OpenFOAM was optimised for the narrow geometry and unique boundary features of the ONSAS, yielding high-resolution maps of CSF flow dynamics. Multiple drainage scenarios were simulated to represent healthy, NTG, and IIH conditions. Area-averaged CSF velocities were quantified for each condition and compared with the scarce and available values reported in phase-contrast MRI (PC-MRI) studies. The results provide novel, physiologically relevant insights into CSF transport behaviour in the ONSAS under different physiological and pathophysiological conditions, with potential implications for the diagnosis, management, and treatment of optic neuropathies.
Myasthenia gravis (MG) is a rare autoimmune neurologic disorder with a heterogenous disease presentation. The objective of this targeted literature review was to characterize the burden of disease and unmet treatment needs in patients with MG. Scientific articles published in English between May 4, 2013, and November 24, 2025, were identified in the PubMed, Medline, Embase, and Cochrane Library databases using a pre-defined Boolean search strategy. Titles and abstracts were screened for information on clinical presentation, pathology, and diagnostic considerations for MG; burden of disease, including epidemiologic, clinical, humanistic, and economic burden; and treatments, including treatment guidelines. The analysis included 318 records. Population-based estimates of MG incidence published from 2007 onwards ranged from 0.3 to 6.1 per 100,000 person-years, and prevalence estimates ranged from 2.2 to 58.6 per 100,000 persons. The clinical and humanistic burden of MG remains high, with patients reporting inadequate symptom control, fatigue, poor quality of life, and dissatisfaction with their current treatment. Greater disease severity was associated with reduced quality of life and poorer mental health. Medical costs varied by region, and key drivers of direct medical costs include hospitalization and treatment of exacerbation or myasthenic crisis. The burden of MG remains high, despite the availability of novel treatments. Studies are needed to better characterize the current burden of MG in the context of newer treatment options and to explore how the disease burden may be reduced for patients.
Metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD) has emerged as a new subtype of steatotic liver disease, and presents a substantial challenge in clinical trial design due to a lack of data and consensus on endpoint selection. This review proposes patient selection, stratification, and optimization in Phase II and III clinical trial designs for MetALD and provides reasonable stage-specific clinical trial endpoints. It provides a comprehensive review of data on non-invasive tests (NITs) and trial endpoints in metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, and extrapolates these data to MetALD. The design of effective MetALD trials necessitates rigorous stratification by fibrosis stage and drinking patterns. In pre-cirrhotic MetALD, NITs, including vibration-controlled transient elastography, magnetic resonance elastography, and magnetic resonance imaging-proton density fat fraction, are reliable surrogate endpoints, with each modality-specific cut-off set to meet clinical improvement targets. For patients with compensated or decompensated cirrhosis, the emphasis shifts to hard clinical outcomes, such as transplant-free survival, overall survival, and prevention of major adverse liver events in phase III clinical trials. Additionally, integrating alcohol-reduction endpoints and comprehensive cardiometabolic endpoints is essential to capture the full impact of interventions in clinical trials. The MetALD clinical trials require strategic design, the adoption of the NITs shift concept, and stage- and phase-specific endpoints.
Abstract Background Common mental health disorders contribute to global disability, yet improving mental health outcomes is rarely a goal of nutrition policy. There is emerging evidence that links food insecurity, diet quality, ultra-processed foods, and microbiota-gut-brain pathways with mental health. This policy document analysis examined how evidence on the relationship between diet and mental health is reflected in national dietary guidelines and large-scale nutrition and social protection programme documents. Methods Using Population-Concept-Context criteria and document analysis procedures guided by Arksey and O’Malley and Joanna Briggs Institute, and PRISMA extension for scoping review reporting principles, we identified selected national food-based dietary guidelines and flagship programme or policy documents (2000–March 2026) and examined whether and how they contained language related to mental health. These documents were retrieved from the portals of the Food and Agriculture Organization of the United Nations and the United Nations Children’s Fund, UN agency repositories, and national or federal websites. The sample was multi-region but not an exhaustive census of all national dietary guidelines globally. We then synthesised data descriptively on characteristics, mental health framing, indicators, mechanisms, and equity. Results Nineteen documents met the criteria, including nine national guidelines, one global FBDG review, and nine programme and policy documents. Most documents were ‘silent’ or ‘symbolic’, using generic language about well-being or learning without clearly mentioning mental health outcomes, indicators, or mechanisms. The only exceptions were the U.S. National Strategy on Hunger, Nutrition, and Health and the Rural Health Produce Prescription Toolkit, which showed emergent integration by linking food insecurity to anxiety, depression, and toxic stress. Conclusion The science of the link between diet and mental health remains largely absent from formal nutrition guidance. Future revisions to guidelines and programmes should incorporate mental health outcomes and shared indicators across diverse high- and low-income settings.
We compared demographic and clinical characteristics of patients with gastroenteropancreatic (GEP) and lung neuroendocrine tumors (NETs) enrolled in the NET-PRO study to those in the U.S. Surveillance Epidemiology and End Results (SEER) program to evaluate the comparability of NET-PRO as a resource for real-world evidence generation and patient reported outcomes (PROs). NET-PRO enrolled adults with GEP or lung NETs from 14 health systems between 2018 and 2024. SEER data included patients diagnosed with NETs from 2018 to 2021 across 22 U.S. cancer registries. We compared age, sex, race/ethnicity, tumor site, stage, and surgery between cohorts using standardized mean differences (SMDs), with values ≥ 0.2 interpreted as meaningful. We analyzed 1,974 GEP-NET and 394 lung NET patients in NET-PRO versus 38,942 and 11,265, respectively, in SEER. Most demographic and clinical characteristics were broadly similar between cohorts, with trivial differences by sex (SMDs 0.16–0.22) and moderate differences in mean age (SMD = 0.47 for lung NETs). Race/ethnicity differences were larger, with Non-Hispanic White patients overrepresented in NET-PRO (SMDs 0.53–0.84). Tumor site and stage distributions differed modestly. Surgery rates were comparable for GEP-NETs but higher among NET-PRO lung NET patients (SMD = 0.47). NET-PRO demonstrates broadly comparable demographic characteristics to SEER across factors such as age and sex. While race/ethnicity differences highlight areas for improved inclusion, other areas of variation suggest important future research covariates. These findings support the contextual comparability of NET-PRO with the broader NET population and its value as a resource for real-world evidence generation. NCT05064150 (Start Date: 2022-05-10).
