Ana María García-Muñoz

Neurodegenerative diseases arise from interacting oxidative, inflammatory, mitochondrial, and proteostatic disturbances. Hydroxytyrosol (HT), an olive phenol, has been proposed as a multitarget neuroprotective compound. This narrative review integrates HT chemistry, parent/metabolite pharmacokinetics, blood–brain barrier (BBB) evidence, mechanisms, disorder-specific models, and human studies. Direct HT evidence is strongest for nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) activation and experimental modulation of α-synuclein; support for AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial protection, nuclear factor-kappa B (NF-κB)-related inflammation, and amyloid-β (Aβ) is predominantly preclinical, whereas tau, autophagic flux, and ubiquitin–proteasome effects remain preliminary. Oral HT is rapidly absorbed but extensively conjugated, and no study has quantified parent HT or its major metabolites in the human brain or cerebrospinal fluid after oral supplementation. Isolated-HT trials show systemic antioxidant or anti-inflammatory biomarker effects, while cognitive findings derive mainly from phenolic-rich olive matrices and cannot be assigned to HT alone. No disease-modifying efficacy has been established for isolated HT in Alzheimer’s disease (AD), Parkinson’s disease (PD), or related disorders. HT is therefore a mechanistically plausible candidate, but human brain exposure, dose–response, and efficacy require adequately powered disease-specific trials.

Diabetic retinopathy, diabetic kidney disease, and diabetic peripheral neuropathy remain major causes of visual loss, kidney failure, pain, disability, and reduced quality of life despite improvements in glycemic and cardiovascular risk management. Oxidative stress, mitochondrial dysfunction, iron dyshomeostasis, lipid peroxidation, and sterile inflammation are shared features of these complications and converge on regulated cell-death programs. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 and complementary antioxidant systems are insufficient, whereas pyroptosis is an inflammatory lytic process executed by gasdermins after activation of inflammasome-associated or other inflammatory caspases. Nuclear factor erythroid 2-related factor 2 (NRF2) connects these pathways by regulating glutathione synthesis, lipid peroxide detoxification, iron handling, mitochondrial homeostasis, and redox-sensitive inflammatory signaling. Dietary polyphenols may influence this network through electrophilic or kinase-dependent NRF2 activation, preservation of the SLC7A11-glutathione-GPX4 axis, modulation of iron and lipid metabolism, and inhibition of NF-kappaB, TXNIP, NLRP3, caspase-1, and gasdermin signaling. This integrative review critically examines mechanistic, preclinical, and human evidence for these effects in the diabetic retina, kidney, and peripheral nerve. The strongest direct preclinical evidence currently concerns corilagin, resveratrol, isoquercetin, quercetin, epigallocatechin gallate, punicalagin, and selected anthocyanin-rich or phenolic extracts. Human studies suggest possible benefits for albuminuria, retinal edema, endothelial function, and neuropathic outcomes, but they rarely measure ferroptosis- or pyroptosis-specific biomarkers and their results are heterogeneous. The proposed ferroptosis–pyroptosis–NRF2 network should therefore be viewed as a biologically plausible integrative framework rather than a clinically validated linear pathway. Future trials require chemically characterized interventions, exposure biomarkers, tissue-relevant pharmacokinetics, prespecified regulated-cell-death panels, and clinically meaningful microvascular endpoints.

Background/Objectives: Automated insulin delivery (AID) systems have improved the management of type 1 diabetes (T1D), but exercise and nutrition remain challenging because they rapidly alter glucose flux, substrate oxidation, hepatic glucose output, insulin requirements, and fuel availability. This narrative review aimed to synthesize current evidence on the interaction between AID systems, physical activity, and nutritional strategies from a metabolism-oriented perspective. Methods: A narrative bibliographic approach was used to integrate evidence from clinical trials, observational studies, technical studies, consensus statements, and reviews involving people with T1D across different life stages, including pediatric, adolescent, adult, and pregnancy-related contexts, when available. The review focused on AID systems, exercise physiology, nutritional strategies, meal announcement, bolus adjustment, dual-hormone systems, metabolic biomarkers, and emerging metabolomic approaches. Results: AID systems generally improve time in range and reduce hypoglycemia across several user groups, although most exercise- and nutrition-specific evidence comes from adult and pediatric/adolescent cohorts rather than pregnancy-specific exercise studies. Exercise-related glucose responses remain highly dependent on user input, exercise modality, insulin on board, meal timing, and metabolic state. Planned exercise announcement, prandial bolus reduction before postprandial activity, and individualized carbohydrate intake remain key strategies. Biomarkers such as lactate, ketone bodies, non-esterified fatty acids, and counter-regulatory hormones may help explain interindividual variability and support future personalization. Conclusions: Nutrition and exercise management in AID users should be interpreted as a dynamic metabolic interface among exogenous insulin, endogenous counter-regulation, substrate availability, and algorithmic control. Emerging approaches, including activity sensors, adaptive algorithms, dual-hormone systems, digital twins, and metabolomics-informed personalization, may improve safety and reduce user burden, but several remain exploratory and require further validation in diverse free-living conditions.

To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and CENTRAL were searched from inception to 28 February 2026 for randomised controlled trials of oral probiotics, prebiotics, or synbiotics in participants aged ≤ 19 years with type 1 diabetes. Primary outcomes were glycated haemoglobin, fasting blood glucose, total daily insulin dose, and C-peptide. Immune-inflammatory, microbiota-related, intestinal permeability, and safety outcomes were narratively synthesised. Twelve randomised controlled trials involving 808 paediatric participants were included. Interventions varied in formulation, dose, and duration. Pooled analyses showed significant reductions in glycated haemoglobin and fasting blood glucose, whereas no significant effects were found for total daily insulin dose or C-peptide. Immune-inflammatory, microbiota-related, and intestinal permeability outcomes suggested possible benefits, but reporting was inconsistent and quantitative pooling was not feasible. Overall, the evidence was limited by substantial clinical and methodological heterogeneity. Conclusion: Gut microbiota-modulating interventions may improve glycaemic control in children and adolescents with type 1 diabetes, particularly glycated haemoglobin and fasting blood glucose. However, current evidence is insufficient to support any specific formulation, dose, or duration, and larger well-designed paediatric trials are still needed. What is Known: • Gut microbiota-modulating interventions are biologically plausible adjunctive strategies in paediatric type 1 diabetes. • Earlier paediatric reviews included few randomised trials and reported inconsistent glycaemic findings. What is New: • This updated review included 12 randomised controlled trials involving 808 children and adolescents. • It adds a structured synthesis of immune-inflammatory, microbiota/barrier, metabolite-related and safety outcomes beyond glycaemic endpoints.

Background: Autism spectrum disorder (ASD) is consistently associated with a high prevalence of sleep disturbances across the lifespan, with reported rates ranging from 60% to 86% depending on age and clinical characteristics. Although this issue has been widely described in the international literature, Spain currently lacks large-scale data to estimate the prevalence of sleep disturbances or to examine their relationship with factors such as age, intellectual disability, and co-occurring conditions. This study aims to estimate the prevalence and severity of sleep disturbances in individuals with autism spectrum disorder in Spain and to examine their associations with developmental stage, intellectual disability, affective symptoms, and contextual factors. Methods: This is a cross-sectional observational survey with nationwide dissemination approved by the Ethics Committee of the Universidad Católica San Antonio de Murcia. Data will be collected through an online survey (SurveyMonkey) including validated instruments: the Children’s Sleep Habits Questionnaire–Autism (CSHQ-Autism) and the Sleep Disturbance Scale for Children (SDSC) for pediatric participants; the Pittsburgh Sleep Quality Index (PSQI) for adolescents and adults without intellectual disability; and the Diagnostic Assessment for the Severely Handicapped–II (DASH-II) for adults with intellectual disability. Anxiety and depressive symptoms will be assessed using the Child Behavior Checklist (CBCL) in children and adolescents and the Hospital Anxiety and Depression Scale (HADS) and DASH-II. Statistical analyses will be conducted using SPSS v22 by applying parametric or non-parametric tests according to data distribution. Conclusions: This study represents one of the first survey protocols with nationwide dissemination designed to assess sleep disturbances in individuals with ASD in Spain. The resulting findings are expected to help identify vulnerability profiles, inform public health strategies, and support the development of multidisciplinary interventions aimed at improving sleep and, consequently, the quality of life of individuals with autism and their families.

We thank the authors of the Comment for their careful reading of our article and for raising important interpretative and methodological considerations

Introduction: Cognitive impairment and age-related cognitive decline are major public health concerns, and nutraceutical strategies targeting modifiable biological pathways have attracted growing interest. Compounds derived from the Zingiberaceae family, including curcumin, turmeric, ginger, and related preparations, have been investigated for their potential neuroprotective effects, but their clinical impact on specific cognitive domains remains unclear. This systematic review and meta-analysis aimed to evaluate the effects of Zingiberaceae-derived interventions on memory-related and other cognitive outcomes in adults. Methods: A systematic search was conducted in MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to March 2026. Randomized controlled trials evaluating orally administered Zingiberaceae-derived interventions in adults and reporting validated cognitive outcomes were included. Cognitive outcomes were grouped into memory-related outcomes, executive function and processing speed, global cognition, and attention or inhibitory control, with memory-related outcomes prespecified as the primary outcome. Results: Eighteen randomized, double-blind, placebo-controlled clinical trials were included in the qualitative synthesis, and domain-specific meta-analyses were performed when at least three studies were available. In the pooled analysis, Zingiberaceae-derived interventions showed a statistically significant improvement in memory-related outcomes (standardized mean difference = 0.57; 95% confidence interval: 0.13 to 1.02), whereas no significant pooled effects were observed for executive function and processing speed, global cognition, or attention or inhibitory control. Sensitivity analyses were consistent with the main findings. Discussion: Overall, Zingiberaceae-derived interventions may improve memory-related outcomes, but the evidence is very uncertain due to substantial heterogeneity, the small number of studies, risk of bias in some trials, and variability in populations, formulations, and outcome measures. These findings indicate that their cognitive effects may be domain-specific and context-dependent, highlighting the need for larger, well-designed trials using standardized cognitive endpoints and bioavailable formulations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261325966 , identifier CRD420261325966.

1. Alopecia is a prevalent condition frequently associated with diminished quality of life and increased psychological distress (1,2). Its pathology is broadly categorized into scarring (permanent)...

Cardiovascular disease is a leading cause of global morbidity and mortality, and processed meat consumption has been consistently associated with adverse cardiometabolic outcomes in observational studies. However, processed meat products differ substantially in composition and processing methods, and traditional dry-cured ham presents distinct nutritional and biochemical characteristics. This systematic review and meta-analysis aimed to synthesize evidence from human intervention studies evaluating the effects of dry-cured ham consumption on cardiometabolic and vascular health in adults. A comprehensive search of major databases identified eligible randomized and non-randomized intervention studies. Five trials were included in the qualitative synthesis, and meta-analyses were performed for blood pressure, lipid profile, and fasting blood glucose outcomes when sufficient data were available. The pooled analyses indicated a small but statistically significant reduction in diastolic blood pressure and total cholesterol associated with dry-cured ham consumption, whereas no significant effects were observed for systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, or fasting blood glucose. Substantial heterogeneity was present across most outcomes. Overall, the available intervention evidence suggests that dry-cured ham consumption at doses ranging from 40 to 120 g/day does not appear to adversely affect conventional cardiometabolic risk markers in adults. Nevertheless, the limited number and short duration of trials warrant cautious interpretation.

Background: Roux-en-Y gastric bypass (RYGB) is a highly effective treatment for severe obesity, achieving substantial weight loss and metabolic improvement. Beyond weight, assessing body composition and functional markers is essential. Phase angle (PA), obtained through bioelectrical impedance, is a relevant indicator of cellular integrity and nutritional status. The rise of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GLP-1 and GLP-1/GIP) agonists makes comparison with surgical outcomes increasingly important. This study aimed to evaluate changes in fat mass, lean mass, hydration, and PA after RYGB and compare these findings with evidence from pharmacological therapies. Methods: A retrospective observational study was conducted in 15 patients (18–50 years, BMI > 35 kg/m²) at Quirón Salud Hospital Torrevieja. Body composition was assessed using multifrequency bioelectrical impedance (TANITA BC-980) before surgery and at 3 and 12 months. All patients received structured nutritional follow-up. Repeated-measures ANOVA and the Friedman test were applied. Results: After 12 months, weight decreased by 40.06 ± 11.86 kg; fat mass by 30.43 ± 10.81 kg; and fat-free mass by 9.64 ± 5.31 kg. PA declined 11% during the first 3 months and then stabilized. Women lost more fat mass; men lost more lean mass. Conclusions: RYGB combined with nutritional support produces high-quality weight loss with relative preservation of lean tissue and stabilization of PA, which proves valuable for postoperative monitoring.