.
Abstract Background Rare diseases affect over 300 million people worldwide but have historically lacked dedicated global governance within the World Health Organization (WHO). Efforts remained fragmented, with no unified framework or accountability mechanism. Objective This commentary analyses the significance, opportunities, and implementation challenges of the first-ever WHO resolution on rare diseases (WHA78.11), unanimously adopted on 27 May 2025 and co-sponsored by Egypt and Spain. Key Content of the Resolution The resolution designates rare diseases as a global health priority for equity and inclusion. It urges the development of a comprehensive 10-year Global Action Plan (GAP), integration of rare diseases into Universal Health Coverage (UHC), strengthened registries and coding systems, patient-centred care pathways, and meaningful involvement of patient organizations. It also establishes reporting mechanisms, with progress updates expected in 2026, 2028, and 2030. Critical Analysis While the resolution represents a historic milestone and provides a much-needed governance framework, significant challenges remain. These include insufficient sustainable financing (particularly in low- and middle-income countries), slow preparatory progress, heterogeneity across Member States, limited interoperable data systems, and the tension between innovation and affordability. Measurable success will depend on strong governance structures, innovative financing mechanisms, robust data management, and the development of clinical care pathways. Conclusions WHA78.11 marks the first lap in a long marathon toward equitable care for persons living with rare diseases. Its ultimate impact will be determined by the timely development and effective implementation of the Global Action Plan, with clear, time-bound targets and adequate resource allocation. The coming months, particularly the report to the 79th World Health Assembly in May 2026, will be critical.
Acrylamide (ACR), a common environmental and dietary neurotoxicant, exerts profound deleterious effects on the central nervous system by triggering oxidative stress, neuroinflammation, apoptosis, and motor impairments. Eugenol (EU), a natural phenolic compound known for its antioxidant and anti-inflammatory properties, was evaluated for its neuroprotective efficacy in ACR-induced brain toxicity in rats. Male Wistar rats were orally administered ACR (20 mg/kg/day) for four weeks to induce neurotoxicity, with concurrent administration of EU at two doses (50 and 100 mg/kg/day). Behavioral assessments, including foot splay, gait score, and rotarod performance, were conducted to evaluate motor coordination and neuromuscular integrity. Biochemical analyses revealed that ACR significantly elevated markers of oxidative and nitrosative stress, suppressed antioxidant defense mechanisms. Furthermore, ACR induced significant upregulation of pro-inflammatory mediators (NLRP3, p-NF-κB, IL-1β), as well as apoptosis markers such as caspase-3, alongside prominent histopathological alterations and astrocyte activation (evidenced by increased GFAP expression). Treatment with EU resulted in a dose-dependent amelioration of these neurotoxic effects. Notably, EU restored motor function, attenuated oxidative/nitrosative damage, and reactivated the Nrf2/NQO1/HO-1 antioxidant pathway. Simultaneously, it significantly downregulated the expression of NLRP3, p-NF-κB, and IL-1β, indicating strong anti-inflammatory action. Histological analysis confirmed preservation of neuronal architecture, while immunohistochemistry showed reduced caspase-3 and GFAP expression in EU-treated groups. These findings suggest that EU exerts potent neuroprotective effects against ACR-induced brain toxicity, primarily through modulation of redox balance, suppression of neuroinflammation, and inhibition of apoptotic cell death, via targeting both the Nrf2-mediated antioxidant system and the NLRP3/NF-κB/IL-1β inflammatory cascade.
Prenatal and early childhood exposure to pesticides is a global concern, yet the genotoxic mechanisms potentially linking these exposures to adverse health outcomes remain incompletely characterized. We conducted a systematic review and random-effects meta-analysis of studies reporting primary DNA damage, cytogenetic damage, DNA methylation, or gene expression outcomes associated with prenatal and early childhood pesticide exposure. We searched four databases following PRISMA guidelines and assessed using risk of bias using the Newcastle-Ottawa Scale. Twenty-eight studies met inclusion criteria. Meta-analysis revealed substantial DNA damage in pesticide-exposed groups (Cohen's d = 4.85, 95%CI = 3.31-6.39), with stronger effects in maternal and cord blood than in children's blood. Cytogenetic damage showed consistent increases in agricultural versus urban areas, though with significant heterogeneity in effect magnitude. Pathway-specific gene expression analysis revealed significant downregulation of DNA damage/repair genes (-1.08, 95%CI:-1.20,-0.96) and distinct biological responses across inflammatory, oxidative stress, and cell signaling pathways. DNA methylation responses varied by pesticide class, with o,p'-DDT consistently associated with hypermethylation. Pronounced sex-specific effects and genetic susceptibility emerged as important effect modifiers. The evidence supports substantial genotoxic and epigenetic alterations following early-life pesticide exposure, highlighting mechanistic pathways that may underlie adverse health outcomes and reinforcing the need for precautionary policies during critical developmental windows.
Vitex agnus-castus L. (chaste tree) has a rich history of use in traditional medicine across various cultures for over 2500 years, particularly for gynecological issues. Its applications range from regulating menstrual cycles to alleviating premenstrual syndrome and menopausal symptoms, with endorsements from health authorities such as the German Commission E. This review aims to consolidate existing knowledge on the ethnopharmacological uses, phytochemistry, and pharmacological effects of V. agnus-castus, while also discussing its safety profile and therapeutic potential. The relevant articles were identified by searching PubMed ( www.pubmed.com ), Scopus ( http://www.scopus.com ), ISI Web of Science ( www.webofknowledge.com ), and Google Scholar ( www.scholar.google.com ) up to November 2024. V. agnus-castus exhibits a wide range of pharmacological properties, including antioxidant, anti-inflammatory, antimicrobial, and cytotoxic effects. Its active compounds, particularly casticin, have been linked to these benefits. Future research should focus on advanced preclinical and clinical studies to better assess its safety and therapeutic efficacy in diverse populations.
Introduction While pathogen genomics using next-generation sequencing (NGS) has been recommended by the WHO as an essential tool for national communicable disease surveillance programmes, procurement and supply chain management (PSM) systems for this new technology are still evolving. To assess the status of PSM systems for pathogen genomics, we examined perspectives from end-users and manufacturers across South and Southeast Asia.Methods Between 2022 and 2023, a cross-sectional survey was conducted among institutional partners supporting pathogen genomics among primarily low- and middle-income countries in South and Southeast Asia. This was complemented by qualitative interviews with the major regional NGS manufacturers. A PSM framework was employed to assess sales, procurement, production, distribution and post-sales support. Analyses are expressed as proportions and means or medians for continuous variables.Results A total of 42 partners across 13 countries, 3 genomics manufacturers and 22 laboratory personnel contributed data to this assessment. PSM challenges were reported by all countries and for all sequencing platforms. High costs of equipment and consumables were identified by 85% of respondents. Long equipment purchasing lead times and reagent re-supply times were reported by 69% and 77% of countries, respectively, with reagent resupply times averaging 8 weeks (IQR 6.2-9.0). Additional barriers included customs clearance, variability of import procedures, taxes and duties. Manufacturers reported a range of strategies to respond to PSM bottlenecks, including establishing regional hubs, distributor networks and financing schemes.Conclusion Coordinated national and regional efforts are required to improve PSM systems for pathogen genomic sequencing to enhance timely early disease detection and response capacity in South and Southeast Asia.
