Hospital Universitari de Santa Maria

Exposomic determinants substantially influence the variability of molecular IgE-mediated sensitization in allergic rhinitis and conjunctivitis across bioclimatic regions, underscoring their relevance in precision allergology. This study aimed to characterize molecular sensitization profiles in Spanish patients with respiratory allergy from distinct geographic and climatic areas. A cross-sectional, multicenter study was performed in 12 Spanish cities. The study population comprised 291 patients diagnosed with allergic rhinitis and/or conjunctivitis according to the modified ARIA/DECA criteria. Participants underwent skin prick testing with standardized allergen extracts and multiplex molecular IgE analysis. Clinical, demographic, and regional bioclimatic variables were integrated to define exposomic sensitization patterns. Patients previously treated with allergen immunotherapy or biologics were excluded. Regional pooled sera were analyzed by ELISA and IgE immunoblotting to validate molecular data and identify IgE binding to nonrecombinant or poorly characterized allergenic components. Distinct regional sensitization profiles were identified. Grass pollen allergens predominated in oceanic and continental climates, while olive and cypress pollens were more frequent in Mediterranean areas. Sensitization to house dust mite, particularly Dermatophagoides pteronyssinus and Blomia tropicalis, was highly prevalent in subtropical and humid zones. Molecular assays confirmed skin test findings and identified major allergenic molecules, including Phl p 1, Ole e 1, Der p 1, and Der p 2, along with region-specific components such as Der p 23, Cup a 1, Alt a 1, and Pla a 2. This multicenter exposomic study demonstrated that climatic diversity modulates allergen sensitization in Spain, supporting region-tailored precision diagnostic and therapeutic strategies in respiratory allergy.

Advanced glycation end-products (AGEs) activate specific receptors (RAGE) promoting inflammation and oxidative stress. The lungs, with high RAGE expression, may be particularly susceptible to AGE-related injury. This study assessed whether baseline skin AGE levels, measured by skin autofluorescence (SAF), predict pulmonary function decline in middle-aged adults with cardiovascular risk factors. This ancillary analysis of the ILERVAS cohort included adults aged 45–70 years with cardiovascular risk factors but without diabetes or chronic kidney disease. Baseline data included demographics, lifestyle, and fasting blood tests. SAF was measured using AGE Reader™, and spirometry performed at baseline and after a median follow-up of 4 years. Associations between baseline SAF and annual declines in FEV1, FVC, and FEV1/FVC were analysed using adjusted models and generalized additive models, stratified by smoking status. Among 658 participants (median age 56 years, 48% female), median baseline SAF was 1.90 AU [1.60; 2.20]. Baseline lung function was preserved, with median FEV1, FVC and FEV1/FVC of 2795 mL [2270; 3,341], 3,525 mL [2870; 4300], and 78.6% [74.4; 82.8]. Annual declines were − 81.9 mL [− 120.6; − 43.3] for FEV1, − 99.6 mL [− 159.3; − 37.9] for FVC, and − 0.04% [− 0.85; 0.70] for FEV1/FVC. No significant associations were found between SAF and spirometry changes. Results were consistent across smoking subgroups. Baseline skin AGE levels did not predict pulmonary function decline over four years in middle-aged adults with cardiovascular risk factors. While SAF reflects cumulative AGE exposure, it has limited prognostic value for lung function in this population.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-33414-8.

BackgroundOur objectives were to determine the diagnostic accuracy of plasma p‐tau217 and its discriminative power for the Alzheimer's disease‐related pathology, and to determine the cut‐off that optimize the concordance with Aβ42/Aβ40 positive vs negative status.Method127 patients with AD (n = 30), MCI (n = 81), and non‐AD dementias (n = 16) were included. Aβ42, Aβ40, total tau, and phosphorylated tau181 (p‐tau181) were quantified in CSF and Aβ42, Aβ40, p‐tau181, and p‐tau217 were measured in plasma using the Lumipulse platform (Fujireibio).ResultWe found a significant correlation between plasma levels of p‐tau217 and CSF levels of p‐tau181 (r = 0.539), Aβ42 (r = −0.443), and Aβ42/Aβ40 (r = −0.594). Regarding diagnostic accuracy, the discriminatory power of p‐tau217 in separating AD from non‐AD dementia patients (AUC 0.856, 95% CI 0.715‐0.996) was comparable with CSF Aβ42/Aβ40 (AUC 0.879, 95% CI 0.592‐0.887) and significantly different from plasma p‐tau181 (AUC 0.662, 95% CI 0.500‐0.823). In addition, the plasma levels of p‐tau217 were associated with the brain AD‐related pathology quantified in CSF. Finally, plasma p‐tau217 (AUC 0.919, 95% CI 0.857‐0.981) showed a high consistency with amyloid pathology (CSF Aβ42/40) at ≥ 0.234 pg/mL cut‐off. The two cut‐offs approach (> 0.314 pg/mL positive and < 0.161 pg/mL negative for p‐tau217) revealed that nearly 84.7% of the patients can be diagnosed as negative or positive for p‐tau217 with a sensitivity and specificity of 94.7% and 93.9%, respectively.Conclusionp‐tau217 blood biomarker has a high diagnostic accuracy and, therefore, it can be a useful tool for screening of those patients that will need a lumbar puncture for AD diagnosis.

BackgroundCerebrospinal fluid (CSF) orexin levels are higher in MCI and AD and associated with sleep deterioration, increasing risk of cognitive decline and Alzheimer's disease (AD) progression. Orexin‐A is a key sleep‐wake cycle regulator. Dual orexin receptor antagonists improve sleep in AD and insomnia and may reduce tau and Aβ deposition in older adults. However, little research has investigated associations between sleep microarchitecture, orexin, neurodegeneration biomarkers, cognitive decline, or mental health in AD.MethodsUsing data from a prospective cohort study of mild‐to‐moderate AD (n = 60, 30‐female, mean age‐74.7), we analysed non‐REM sleep spindles, slow oscillations (SO), and their associations with CSF orexin, AD biomarkers, cognition, and mental health over three years. Participants underwent polysomnography (PSG) and CSF draws at baseline, neuropsychological assessment with the Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog) and Neuropsychiatric Inventory (NPI) at baseline and 12 months, and Mini‐Mental Status Examination (MMSE) at baseline, 12, 24, and 36 months.PSG was scored along American Academy of Sleep Medicine guidelines. Spindle and SO detection were performed using in‐house, open‐source software packages developed at Concordia University, following Moelle (2011) recommendations for spindles and Staresina's (2015) recommendations for SO. Associations between SO and spindle characteristics (duration, density, power, amplitude) and orexin, Aβ42 and tau at baseline, and baseline orexin and cognition from baseline to 36 months were investigated with false discovery rate‐adjusted generalised linear models, controlling for age, sex, apnea‐hypopnea index.ResultsWe found previously unreported, predictive associations between SO, duration, density, amplitude, and CSF orexin. Orexin also predicted increased ptau181, total‐tau, ptau/Aβ42, total‐tau/Aβ42. Increased orexin predicted worse cognitive performance (higher ADAS‐cog, lower MMSE) from baseline to 36‐months and increased neuropsychiatric symptom severity (NPI) from baseline to 12 months. Orexin also moderates relationships between spindles, SO, cognition, and mental health.ConclusionsOrexin levels are associated with neurodegeneration biomarkers and cognitive deterioration in AD and moderate relationships between sleep microarchitecture and cognitive changes over time. Orexin may thus constitute a potential target for sleep‐related interventions for cognition in neurodegenerative disorders.

BackgroundABvac40 is an investigational vaccine targeting Aβ40 for the treatment of Alzheimer’s disease (AD). Aβ40 plays a significant role in several pathological processes of AD, especially concerning amyloid deposition in blood vessels. Phase 2 trial results (NCT03461276) demonstrated a favorable safety profile, robust immunogenicity, and promising trends in cognitive outcomes and brain atrophy. To further explore the therapeutic potential of ABvac40, we aimed to assess clinical relevance at individual patient level by evaluating meaningful within‐patient changes (MWPC). This approach examines the proportion of patients experiencing significant deterioration across treatment groups, providing a method to assess the meaningfulness of treatment effects in progressive conditions like AD.MethodAB1601 was a randomized, double‐blind, placebo‐controlled phase 2 study in patients with mild cognitive impairment or very mild AD. MWPC was defined as a decline of ≥3 points in MMSE at two consecutive visits over 24 months. Cox proportional hazard models assessed the risk of MWPC, adjusting for MMSE baseline score, baseline age, APOE Ɛ4 carrier status, clinical stage and baseline use of AD medication. Patients treated with ABvac40 were stratified by CSF antibody levels into two groups: high levels (Q4) and low levels (Q1–Q3). Analyses were conducted in the PPc analysis set.ResultA total of 97 patients were included in the PPc analysis set. Of these, 69 (71.1%) were amyloid‐PET positive. In the overall population, ABvac40 significantly reduced the risk of MWPC over 24 months compared to placebo (HR=0.47; 95% CI 0.27–0.85; P=0.012). In the amyloid‐PET positive subgroup, ABvac40 showed a more pronounced protective effect (HR=0.38; 95% CI 0.20‐0.75; P=0.005). Within this subgroup, patients with lower antibody levels had a 63% lower risk of MWPC (HR=0.37; 95% CI 0.16–0.83; P=0.016), while those with higher antibody levels showed an 81% reduction (HR=0.19; 95% CI 0.04–0.84; P=0.029).ConclusionABvac40 treatment significantly reduced clinically meaningful cognitive decline, particularly in amyloid‐PET positive patients, with the strongest effects in those with the highest antibody levels. These findings highlight ABvac40’s potential to influence disease progression in early‐stage AD and warrant further studies to explore its impact on brain vessels as potential driver of the observed cognitive benefits.

Introducción: el síndrome de burnout en trabajadores ha sido ampliamente estudiado, especialmente en profesionales sanitarios durante la pandemia. Objetivo: proporcionar una descripción general de la evidencia existente sobre el síndrome de burnout en colectivos de trabajadores no dedicados a la salud humana entre 2020-2024. Métodos: revisión de alcance realizada de acuerdo con la Extensión de Revisión de Alcance de las Directrices PRISMA. Búsqueda bibliográfica en las bases de datos PubMed y Web of Science el 2 de enero de 2025. Se utilizó la herramienta de Joanna Briggs Institute para estudios de cohortes en la valoración de la calidad metodológica. Resultados principales: 12 de los 494 estudios obtenidos cumplían los criterios de inclusión, sumando 12612 participantes de diferentes profesiones, los estudios de origen asiático aportaron la mayoría de participantes, 77.1% (N=9723). El 42% de los estudios se realizaron en Europa. El 50% utilizó el Maslach Burnout Inventory o alguna de sus variantes en la determinación del burnout i un 58.3% de los estudios correlacionaron el burnout con otros problemas psicosociales y otras variables. Conclusión general: los factores intervinientes en el burnout van más allá de la COVID-19, también en colectivos de trabajadores no sanitarios, sugiriendo causas estructurales e intrínsecas organizacionales. La futura investigación debe enfocarse en estudios longitudinales que identifiquen las relaciones causales y que permitan diseñar y evaluar intervenciones en las empresas, para prevenir y evitar problemas de salud psicosocial en los trabajadores, implicando a otros colectivos y regiones para obtener una perspectiva global completa.