Childhood cancer survival exceeds 80% in high-income countries but remains below 50% across much of Latin America. In Ecuador, limited access to diagnosis and essential medicines, and fragmented governance have hindered progress. In 2025, Ecuador became the first country in the Region of the Americas to implement the Global Platform for Access to Childhood Cancer Medicines, an initiative led by the World Health Organization (WHO) and St. Jude Children's Research Hospital to ensure equitable access to quality medicines while strengthening health systems.

Between 2023 and 2025, Ecuador's Ministry of Public Health, the Pan American Health Organization (PAHO), WHO and St. Jude codesigned a participatory implementation plan. A national situational analysis guided the 2024-2026 roadmap and focused on governance, regulatory alignment, supply-chain optimization and workforce capacity. Key operational tools included medicine forecasting and quantification methodologies, developing standardized treatment protocols, and coordinating with the immunization program's cold-chain infrastructure.

The initiative catalyzed the creation of the National Commission for Childhood and Adolescent Cancer, integration of all prioritized oncology medicines into the national formulary, and consensus in national treatment protocols. Strengthened logistics reduced delivery times for medicines to less than 96 hours, and chemotherapy management training established a foundation for continuing education. Ecuador became the first country in the Region to receive medicines for childhood cancer procured through the Global Platform.

Implementation of the Global Platform in Ecuador has strengthened pediatric oncology and positioned it as a national health priority. By coupling medicine access with systemic reform, Ecuador has demonstrated that collaborative governance, intersectoral coordination and political commitment can build sustainable capacity to deliver equitable childhood cancer care.

To assess the market landscape of penicillin formulations used for the treatment of syphilis and rheumatic heart disease in the World Health Organization South-East Asia Region.

We analysed market data for five essential penicillin formulations across nine countries in the South-East Asia Region using a survey form to collect data on product registration, inclusion in national essential medicines lists, procurement, availability, pricing and demand forecasting.

Substantial disparities exist in registration status, procurement and pricing across the region. The price of benzathine benzylpenicillin 1.2 million international units (IU) in Timor-Leste was over 23 times higher than in Bangladesh (3.45 United States dollars, US$, versus US$ 0.15), while the price for 2.4 million IU varied by up to 55-fold across the region. Several countries reported supply issues, including shortages of benzathine benzylpenicillin in India, Maldives, Myanmar, Thailand and Timor-Leste; aqueous benzylpenicillin in Sri Lanka during the 2022 economic crisis; and supply disruptions of phenoxymethylpenicillin 250 mg in Maldives and Sri Lanka. Morbidity-based estimates indicated annual regional demand of 171 966 061 vials of benzathine benzylpenicillin 2.4 million IU and 923 053 121 tablets of phenoxymethylpenicillin 250 mg, with corresponding costs of US$ 62 127 441 and US$ 48 005 181, respectively. India has the highest demand of these two formulations.

Differences in registration, procurement, pricing and forecasting undermine reliable access to penicillin products in the South-East Asia Region. Stronger regional collaboration, improved forecasting, harmonized regulatory approaches and pooled procurement strategies are needed to secure equitable and sustainable access.

Ischemic stroke triggers neuroinflammation and oxidative stress, leading to neuronal damage. Kojic acid (KA) has exhibited neuroprotective properties in other neurological pathologies but suffers from poor bioavailability. This study investigated whether KA encapsulated in nanostructured lipid carriers (KA-NLC) exerts protective effects against cerebral ischemia.

Eighty adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) or control procedures and allocated into 10 experimental groups (n = 8 per group): intact, sham, MCAO, vehicle, three free-KA solution groups (10, 20, and 40 mg/kg), and three KA-NLC groups (1, 2, and 4 mg/kg). Functional outcomes were assessed using neurological scoring and Rota-Rod, Morris water maze, and shuttle box tests. Brain water content, hippocampal histology, and cerebrospinal fluid cytokine levels (interleukin-10 [IL-10], tumor necrosis factor-α [TNF-α]) were also evaluated.

Treatment with low and medium doses of KA-NLC and medium and high doses of free KA significantly reduced brain edema and improved neurological scores, motor coordination, and memory performance compared to the MCAO group. These functional improvements were associated with a significant increase in anti-inflammatory IL-10 and a modulation of TNF-α. Histological examination confirmed neuroprotection, with KA-NLC preserving hippocampal CA1 neural integrity. The high dose of KA-NLC and the low dose of free KA however were ineffective.

Nanoformulated KA confers significant neuroprotection against ischemic stroke by reducing edema, modulating inflammation, and preserving neuronal integrity, presenting a promising therapeutic strategy.

Noncommunicable diseases (NCDs) account for approximately 80% of annual mortality in Saint Lucia, with the results of national World Health Organization (WHO) STEPwise approach to NCD risk factor surveillance surveys in 2012 and 2020 indicating increasing prevalences of hypertension, obesity and physical inactivity. In response, the Ministry of Health, Wellness and Nutrition launched the St. Lucia Moves Initiative in 2022, aligned with the Caribbean Moves framework and WHO's Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013-2030. This study aimed to evaluate the implementation, reach, and early outcomes of the Initiative.

A mixed-methods approach was used to assess program implementation and engagement. This approach combined quantitative and qualitative methods to provide a comprehensive understanding of the Initiative's reach, visibility and multisectoral integration. The study was guided by the socioecological model of health promotion, which informed both the analytical framework and the interpretation of findings across all levels.

Key achievements included increased public awareness of physical activity and wellness, broad cross-sectoral participation, and widespread engagement in fitness walks, media campaigns, school-based activities, and integration of the St. Lucia Moves Initiative into national cultural events. Although at the beginning, awareness of the Initiative was limited, it evolved into a recognized national movement within 2 years, supported by collaboration among government, civil society and community groups.

Implementation of the St. Lucia Moves Initiative demonstrates the potential of evidence-based, multisectoral strategies to address the growing burden of NCDs. The program highlights the importance of strong leadership, phased implementation and youth engagement in promoting behavior change. The Initiative provides a promising model for small island developing states seeking to implement coordinated, data-driven approaches to reduce NCD risk factors and improve population health.

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, fatal prion disorder that may initially mimic delirium, metabolic encephalopathy, psychiatric illness, or more common neurodegenerative conditions. Diagnostic recognition is particularly difficult when an acute medical illness provides an apparently plausible explanation for confusion. We report the case of a 74-year-old woman with insulin-dependent diabetes mellitus who was admitted after being found collapsed at home with vomiting and was diagnosed with diabetic ketoacidosis (DKA). Although the metabolic disturbance resolved, collateral history revealed several months of progressive dizziness, gait instability, recurrent falls, and visual hallucinations. During admission, she developed worsening cognitive decline, ataxia, myoclonus, reduced speech output, functional dependence, and eventual incontinence. Initial brain imaging was not diagnostic; however, neuroradiology review identified subtle basal ganglia and thalamic signal abnormalities on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) testing returned positive, supporting the diagnosis of sporadic CJD. This case highlights the importance of reconsidering apparent delirium when neurological decline progresses despite correction of metabolic disturbance or exclusion of infection. Progressive cognitive impairment with hallucinations, ataxia, and myoclonus should prompt evaluation for rapidly progressive dementia, including sporadic CJD.

Diabetes mellitus is a significant risk factor for urinary tract infections (UTIs), which occur more frequently, have a more severe course, and show a greater tendency to recur in affected individuals. Metabolic disturbances, particularly hyperglycemia and glucosuria, promote bacterial growth while simultaneously impairing innate and adaptive immune responses. In addition, diabetes-related complications, such as autonomic neuropathy, contribute to bladder dysfunction and urinary stasis, further facilitating bacterial colonization. Epidemiological evidence indicates a two- to four-fold increased risk of UTIs in patients with diabetes, along with a high prevalence of asymptomatic bacteriuria and recurrent infections. A key feature of this relationship is its bidirectional nature. UTIs can exacerbate glycemic dysregulation by triggering stress responses and increasing insulin resistance, leading to transient or sustained hyperglycemia. Uropathogenic Escherichia coli plays a critical role in the pathogenesis of UTIs, with hyperglycemic conditions further enhancing bacterial adhesion, biofilm formation, and immune evasion. Effective management requires simultaneous control of infection and optimization of glycemic control, particularly in the context of rising antimicrobial resistance. Emerging therapeutic strategies include targeting bacterial adhesion, disrupting biofilms, and modulating host immune responses. Improved understanding of host-pathogen interactions may enable the development of more effective preventive and therapeutic approaches in this high-risk population.

Diabetic foot ulcers (DFU) represent a significant global health burden, drastically reducing quality of life and increasing amputation risk. Associated pain and peripheral vascular disease complicate management and healing. Continuous parasacral ischial plane block (CPIPB), a regional anaesthesia technique targeting the sacral plexus, has shown potential in preclinical studies and feasibility assessments to improve lower limb analgesia and perfusion by modulating sympathetic tone. This trial aims to evaluate the efficacy and safety of CPIPB combined with standard of care (SOC) compared to SOC alone for promoting the healing of chronic DFU.

This study utilizes a single-centre, prospective, randomised, open-label, blinded-endpoint (PROBE) parallel-group design. A total of 78 participants aged 20-89 years with a DFU (University of Texas Classification 1A-2D) present for >4 weeks but <1 year, with an area between 1-20 cm², and adequate perfusion (ABI >0.7 or equivalent) will be recruited after a 2-week SOC run-in period (inclusion requires <30% wound area reduction). Participants will be randomised (1:1) using variable block randomisation to either: 1) CPIPB + SOC: ultrasound-guided catheter placement in the parasacral ischial plane for continuous infusion of 0.2% ropivacaine at 5 mL/h for 14 days, combined with SOC; or 2) SOC alone: including glycaemic control, appropriate debridement, and standard dressings. The primary outcome is the incidence of complete ulcer healing at 12 weeks. Secondary outcomes include time to complete healing, percentage change in ulcer area, proportion achieving ≥50% area reduction, ulcer recurrence, infection rates, pain scores (VAS), lower limb perfusion assessments (TcPO2, Peak Systolic Velocity), health-related quality of life (Wound-QoL), and safety events. Statistical analysis will primarily use the intention-to-treat principle, comparing groups using chi-square tests, t-tests/Mann-Whitney U tests, Kaplan-Meier analysis, and logistic/linear regression models adjusting for baseline covariates where appropriate.

This study aims to evaluate the effects of a 12-week treatment with CPIPB and SOC on patients with DFU. We hypothesize that, compared to SOC alone, CPIPB combined with SOC would significantly improve ulcer healing without provoking significant adverse reactions. These findings potentially pave the way for a safe and effective adjunctive therapy for DFU.

https://www.chictr.org.cn/, identifier ChiCTR2400083504.

This research explored the laboratory indicators and derived indicators of patients with asteroid hyalosis (AH) in patients with diabetic retinopathy (DR), calculated the TyG index and systemic immune-inflammatory (SII) index, so as to identify the systemic pathogenic factors of AH in DR patients.

The data were gained from patients who underwent vitrectomy for proliferative DR (PDR) in Hebei Eye Hospital. Depending on the presence or absence of AH, these participants were classified into the AH group (n = 45; 27 males, 18 females) and the non-AH group (n = 90; 48 males, 42 females). The laboratory indicators, TyG index, and SII index were compared between the two groups. A statistical analysis was implemented on their age, gender, laboratory indicators, TyG index, and SII index.

The patients in the AH group exhibited remarkably higher cholesterol (4.85 vs. 4.09 mmol/L), low-density lipoprotein (2.67 vs. 2.23 mmol/L), triglyceride (1.75 vs. 1.31 mmol/L), TyG index (9.14 vs. 8.77), and fasting blood glucose (6.95 vs. 5.82 mmol/L) levels than the patients of the non-AH group (all P < 0.05); also, the SII index (524.62 vs. 413.66), neutrophils (4.03 vs. 3.45 × 10^9/L), and platelets (256.00 vs. 222.00 × 10 ^ 9/L) significantly differed between groups (P < 0.05). However, the two groups displayed no statistically significant difference in other indicators, including white blood cells, monocytes, and glycosylated hemoglobin (P < 0.05).

The abnormal lipid metabolism, inflammatory activation, and poor glycemic control in patients with AH are more pronounced than in DR patients without AH. Cerebral infarction and AH share overlapping systemic pathological mechanisms.

As the first meal of the day, breakfast significantly impacts the daily blood glucose profile of people with diabetes. However, there is currently no consensus on the optimal macronutrient composition of breakfast (i.e., the appropriate ratio of carbohydrates, protein, fat, and dietary fiber). This systematic review and network meta-analysis aims to evaluate the effects of different macronutrient compositions in breakfast on postprandial blood glucose control in people with diabetes.

We searched the PubMed and Web of Science databases for studies published from the inception of each database through March 23, 2026. We included randomized controlled trials comparing the effects of different breakfast macronutrient compositions on glucose-related outcomes in patients with diabetes. Two researchers independently conducted literature screening, data extraction, and risk-of-bias assessments (using the RoB 2.0 tool). We conducted pairwise and network meta-analyses using a random-effects model. Effect sizes were reported as standardized mean differences or mean differences with 95% confidence intervals. Interventions were ranked using the SUCRA score.

A total of 25 randomized controlled trials were included. Compared with a standard breakfast, adjusting the macronutrient composition of breakfast significantly reduced 2-hour postprandial blood glucose (mean difference = -1.90 mmol/L; 95% confidence interval: -2.46 to -1.34; P< 0.001), glycated hemoglobin (mean difference = -0.52%; 95% confidence interval: -0.59% to -0.45%; P< 0.001), and the area under the postprandial glucose curve (standardized mean difference = -1.24; 95% confidence interval: -2.45 to -0.03; P = 0.045). Subgroup analyses showed that legume-based breakfasts and low-glycemic-index breakfasts were most effective in reducing 2-hour postprandial blood glucose, while breakfasts supplemented with whey protein were most effective in improving HbA1c. Network meta-analysis and SUCRA ranking indicated that legume-based breakfasts (85.7%) and low-glycemic-index breakfasts (71.4%) were the preferred breakfast choices. No significant publication bias was detected, and the results of sensitivity analyses were robust.

Adjusting the macronutrient and dietary fiber composition of breakfast can significantly improve postprandial blood glucose control in people with diabetes. Legume-based breakfasts and low-glycemic-index breakfasts were most effective at lowering 2-hour postprandial blood glucose levels, while breakfasts supplemented with whey protein were most effective at reducing HbA1c.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261367773.

The treatment of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome has largely focused on immunosuppression with little impact on the atopic manifestations of the disease. Dupilumab therapy has been used successfully in primary atopic diseases and immune regulatory disorders to control type 2 inflammation. Indeed, it has been reported in two prior IPEX cases, but in combination with immunosuppressive agents. Here, we are the first to report the clinical and immunologic impact of dupilumab monotherapy in IPEX.

A 4-year-old boy with a confirmed hemizygous Forkhead box protein 3 (FOXP3) missense variant (c.1150G>A; p.Ala384Thr) presented with severe, treatment-refractory atopic dermatitis beginning in the newborn period, failure to thrive, lymphadenopathy, food and environmental allergies, asthma, recurrent febrile neutropenia, and type 1 diabetes mellitus, with a peak IgE of 74,625 IU/mL. Following initiation of dupilumab monotherapy at age 2, the patient had a marked improvement in atopic dermatitis by Eczema Area and Severity Index (EASI) score, a rapid decline in serum IgE, improved growth, reduced respiratory hospitalizations, and a profoundly improved quality of life.

Immunologically, dupilumab effectively suppressed IgE and plasma interleukin-4 (IL-4) and IL-13 to healthy control levels. In addition, C-C motif chemokine ligand 27 (CCL27), important for cutaneous T-cell trafficking, was detected at healthy control levels. Upstream alarmins, eosinophil mediators, T helper 1 (Th1) cytokines, and Treg-specific demethylated region (TSDR) demethylation remained elevated-indicating ongoing systemic immune dysregulation not fully addressed by dupilumab alone.

This case demonstrates that dupilumab monotherapy can effectively suppress the IL-4/IL-13 axis and substantially improve atopic manifestations in IPEX, potentially by restoring skin-specific immune tolerance through rebalancing cutaneous T-cell trafficking. These findings support dupilumab as a targeted adjunctive therapy for the atopic features of IPEX and provide a rationale for the systematic study of dupilumab alone or in combination with other immunosuppression regimens.