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Polygenic risk score of glycemic homeostasis, Type 2 Diabetes Mellitus and glycemic components in first episode psychosis
No full textObjective
First episode of psychosis (FEP) is associated with glucose homeostasis abnormalities even before pharmacological intervention. Given inconclusive GWAS results regarding a direct genetic link between schizophrenia and type 2 diabetes mellitus (T2DM), we hypothesized that FEP patients may exhibit altered genetic risk for glycemic traits. We compared polygenic risk scores (PRS) for T2DM (PRST2DM), fasting glucose (PRSFG), and glycated hemoglobin (HbA1c) (PRSHbA1c) between FEP patients and controls, examining their associations with glycemic measures over 24 months.
Methods
We analyzed data from 242 FEP patients and 119 controls, assessing fasting serum glucose and HbA1c at baseline and 24 months. We examined cross-sectional and longitudinal associations between PRS and glycemic measures within each group.
Results
FEP patients and controls did not differ significantly in PRS. Significant associations were observed for PRSFG with baseline serum glucose in controls (p = 0.008), PRSFG during follow-up (p = 0.034), PRSHbA1c at 24 months (p = 0.018), and HbA1c longitudinally (p = 0.025). After multiple testing corrections, only the association between PRSFG and baseline serum glucose in controls remained significant (p_adj = 0.023). No associations were found for PRST2DM.
Conclusions
Despite the link between FEP and glycemic disturbances, PRST2DM did not differ between FEP patients and controls. However, PRS for glycemic traits showed associations with glycemic measures in both groups before multiple testing correction, suggesting that genetic predisposition may influence glucose homeostasis in early psychosis. The absence of a direct association between common genetic variants underlying T2DM and early glycemic dysregulation in FEP underscores the importance of considering environmental factors and epigenetic mechanisms
Resistance Exercise Intervention Restores Functional Capacity and Improves Frailty Biomarkers in Centenarians
Get PDFBackground: Centenarians comprise an age group characterized by exceptional longevity and low age-associated pathologies. However, they still experience physiological decline, and different studies have linked frailty to this population. Exercise interventions reverse frailty and improve functional capacity, but no studies have addressed the effect of an intervention in centenarians. In this study, we assessed the impact of a 12-week resistance exercise intervention in a group of centenarians and characterized their functional capacity as well as the expression of several molecular biomarkers associated with frailty.
Methods: A total of 19 centenarians were enrolled, but 7 of them did not complete the study. The remaining 12 centenarians were randomly assigned to the control or intervention group, which was a 12-week resistance exercise intervention. Molecular biomarkers were measured by qRT-PCR and ELISA.
Results: The intervention group improved their functional capacity measured by Short Physical Performance Battery (SPPB) (post 5.0 vs 2.3 in pre) and Physical Performance and Mobility Examination (PPME) (6.5 vs 3.8), as well as in frailty status studied by Fried Frailty Phenotype (3.0 vs 3.8) and Frailty Trait Scale 5 (FTS5) (post 30.7 vs 34.0 in pre) scales. ANCOVA revealed that the resistance training led to significant improvements in functional capacity scales SPPB (p = 0.01) and PPME (p < 0.001), as well as Fried Frailty Phenotype (p = 0.001) and FTS5 (p = 0.05). Biomarkers related to frailty (EGR1, miR194-5p, miR125b-5p and miR454-3p) and inflammation (IL-6 and IL-1β) showed different expression patterns in centenarians (n = 19) compared to both old (n = 44, average of 79 years old) and young adults (n = 34, average of 29 years old) groups. Notably, the intervention was associated with improvements in frailty and inflammation biomarkers expression. Finally, correlation analyses showed significant associations between all functional and frailty variables, with SPPB correlating with miR454-3p (ρ = 0.73) and FTS5 correlating with miR454-3p (ρ = −0.83), IL-6 (ρ = 0.60) and miR125b-5p (ρ = −0.55).
Conclusions: Our results revealed that resistance exercise intervention enhances functional status and reduces frailty in centenarians, and this is associated with improvements in frailty and inflammation biomarkers
Compromiso entre tradición y vanguardia en la arquitectura española del primer tercio del siglo XX
No full text¿Cuánto más ejercicio, más sanos? Los adolescentes inactivos muestran peor calidad de vida
No full textCuando pensamos en deporte y salud, solemos imaginar fuerza física y buena condición. Pero el ejercicio también influye en cómo dormimos, nuestro estado de ánimo y nuestras relaciones.
En la adolescencia, una etapa de cambios físicos y emocionales, la práctica deportiva cobra un papel central. Surge la pregunta: ¿es siempre positiva? ¿Qué ocurre cuando pasa de ser ocio a competición? Analizamos a más de 10 000 adolescentes españoles (de entre 11 y 19 años) para encontrar respuestas
Development of the global hydro-economic model (ECHO-Global version 1.0) for assessing the performance of water management options
Get PDFAbstract. Water scarcity is one of the most critical global environmental challenges. Addressing this challenge requires implementing economically-profitable and environmentally-sustainable water management interventions across scales globally. This study presents the development of the global version of the ECHO hydro-economic model (ECHO-Global version 1.0), for assessing the economic and environmental performance of water management options. This global version covers 282 subbasins worldwide, includes a detailed representation of irrigated agriculture and its management, and incorporates economic benefit functions of water use in the agricultural, domestic and industrial sectors calibrated using the Positive Mathematical Programming (PMP) procedure alongside with the water supply cost. We used ECHO-Global to simulate the impact of alternative water management scenarios under future climate and socio-economic changes, with the aim of demonstrating its value for informing water management decision making. Results of these simulations are overall consistent with previous studies evaluating the global cost of water supply and adaptation to global changes. Moreover, these results show the changes in water use and water supply and their economic impacts in a spatially-explicit way across the world, and highlight the opportunities for reducing those impacts through improved water management. Overall, this study demonstrates the capacity of ECHO-Global to address emerging research and practical questions related to future economic and environmental impacts of global changes on water resources and to translate global water goals (e.g., SDG6) into national and local policies
Microfluidic-based 3D culture models for Pancreatic Ductal Adenocarcinoma: unravelling the role of the extracellular matrix and stromal cells
No full textEl adenocarcinoma ductal pancreático (PDAC, del inglés pancreatic ductal adenocarcinoma) es uno de los tumores más agresivos y letales en la actualidad, con una tasa de supervivencia extremadamente baja y una marcada resistencia a las terapias y tratamientos actuales. Un factor clave en estos datos es su denso estroma fibrótico, uno de los componentes del microambiente tumoral (TME, del inglés tumour microenvironment) del PDAC. Este estroma no solo actúa como una barrera física que limita la penetración y efectividad de los tratamientos, sino que también favorece activamente la progresión tumoral. Dentro de este estroma, la matriz extracelular (ECM, del inglés extracellular matrix) y las células estrelladas pancreáticas (PSCs, del inglés pancreatic stellate cells) desempeñan un papel fundamental en la modulación del crecimiento tumoral, la invasión y la resistencia a las diferentes estrategias terapeúticas. Sin embargo, los modelos de cultivo in vitro convencionales no reproducen con precisión la complejidad de los tejidos tumorales, lo que dificulta el estudio de estas interacciones y el desarrollo de estrategias terapéuticas más eficaces. En esta tesis, se ha desarrollado un modelo de cultivo tridimensional (3D) utilizando dispositivos de microfluídica con el objetivo de reproducir y estudiar algunas de las características biomecánicas, estructurales y celulares del microambiente del PDAC. Este sistema integra hidrogeles de colágeno tipo I (Col I) como ECM, PSCs humanas activadas (HPSCs, del inglés human pancreatic stellate cells) y diversas líneas celulares humanas de PDAC (hPDAC), lo que permite estudiar, en un entorno controlado, la autoorganización tumoral, las interacciones con el estroma y las modificaciones inducidas por el microambiente en otros procesos biologicos clave para las células tumorales, mediante técnicas avanzadas de imagen. Uno de los principales retos en el establecimiento de cultivos 3D mantenidos por mayores periodos de tiempo es la generación de fuerzas mecánicas por parte de las células tumorales, las cuales inducen la contracción y remodelación de la ECM, comprometiendo la integridad estructural de los hidrogeles utilizados como matriz.Para solventar esta limitación, durante la presente tesis doctoral se ha optimizado un recubrimiento de polidopamina (PDA) en los dispositivos microfluídicos, mejorando significativamente la adhesión y la estabilidad de los hidrogeles de colágeno a la superficie de los mismos. Esta optimización ha permitido mantener la integridad de la ECM durante periodos de cultivo más prolongados de las células tumorales, asegurando cultivos más estables y condiciones experimentales reproducibles. Con este sistema de cultivo optimizado, se ha investigado cómo las propiedades de la ECM regulan el comportamiento tumoral. Se ha observado que características de la ECM como la rigidez, el tamaño de poro y la permeabilidad hidráulica de la matriz, moduladas por la concentración de colágeno, influyen significativamente en el crecimiento y la organización de los esferoides tumorales. A mayor concentración de colágeno, se favoreció la formación de esferoides más grandes en líneas celulares hPDAC de subtipo clásico, mientras que las células basales requirieron una mayor concentración para autoorganizarse en esferoides más compactos y pequeños. Estas diferencias específicas entre líneas celulares también fueron evidentes al incorporarse las HPSCs al cultivo 3D, para analizar con mayor profundidad las interacciones tumor-estroma. Se observó que las HPSCs ejercen efectos opuestos en las líneas celulares de tipo clásico: en una de ellas favorecieron el crecimiento de los esferoides, mientras que en otra lo inhibieron. En cambio, el impacto sobre las células de tipo basal fue mínimo. Estos resultados subrayan la importancia de tener en cuenta las características específicas de cada línea celular y su microentorno para avanzar en nuestra comprensión del PDAC. Además del impacto sobre el crecimiento y la organización 3D del tumor, también se ha explorado el papel del TME en la regulación de la glicosilación aberrante en los tumores, un proceso clave en la progresión tumoral, la evasión inmune y el potencial metastásico. Los resultados obtenidos revelaron que tanto la interacción con las HPSCs como la arquitectura 3D inherente al tejido tumoral modifican significativamente los patrones de glicosilación, con alteraciones destacadas en la sialilación, la fucosilación y en la expresión de glicoconjugados de tipo N y O. Muchas de estas modificaciones no se detectaron en los cultivos tradicionales bidimensionales (2D), lo que refuerza la necesidad de emplear modelos de cultivo más avanzados, como el presentado en esta tesis, capaces de reflejar con mayor fidelidad la complejidad de los procesos clave implicados en el PDAC. Este trabajo pone de relieve el valor de estos modelos 3D para capturar con mayor precisión la complejidad biológica y mecánica del PDAC, contribuyendo así al desarrollo de estrategias terapéuticas más eficaces, incluidas terapias combinadas desde distintos enfoques biológicos. En conjunto, esta tesis ha desarrollado un modelo 3D versátil que permite avanzar en la comprensión de cómo los componentes del TME modulan procesos esenciales del PDAC. Además de ofrecer un análisis del impacto de las propiedades mecánicas y estructurales de la ECM y las interacciones con células clave del estroma en la progresión tumoral, esta plataforma representa una herramienta valiosa para el futuro desarrollo de estrategias diagnósticas y terapéuticas. La capacidad de reproducir características esenciales del microambiente tumoral en un sistema in vitro controlado facilita la optimización del cribado de fármacos, la medicina personalizada y las terapias dirigidas al estroma.Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies, with a dismal survival rate and resistance to current therapies. A major factor contributing to this resistance is its dense fibrotic stroma, a key component of the tumour microenvironment (TME). This stroma acts as a physical barrier, limiting drug penetration, while also supporting tumour progression. Within this stroma, the extracellular matrix (ECM) and pancreatic stellate cells (PSCs) play pivotal roles in modulating tumour growth, invasion, and therapy resistance. Understanding the complex interplay between TME components is essential for improving diagnostic and therapeutic strategies. Yet conventional in vitro culture models fail to recapitulate the complexity of tumour tissues. We have developed a three-dimensional (3D) microfluidic-based model that mimics key biomechanical and cellular features of the PDAC microenvironment. Our model incorporates collagen type I (Col I) hydrogels as ECM, activated human PSCs (HPSCs), and various human PDAC (hPDAC) cell types. Using advanced imaging techniques, we have investigated tumour self-organisation, stromal interactions, and microenvironment-driven modifications in a controlled setting. A major challenge in establishing 3D cultures is the mechanical forces exerted by tumour cells, which induce ECM contraction, compromising hydrogel integrity. To address this, we have optimised polydopamine (PDA) coatings, significantly enhancing hydrogel adhesion and stability. This ensured consistent ECM integrity, enabling prolonged tumour culture and reproducible experimental conditions. With this system, we explored how ECM properties regulate tumour behaviour. Alterations in matrix properties¿such as stiffness, pore size, and hydraulic permeability¿due to collagen concentration influenced PDAC spheroids growth patterns and organization. Higher collagen concentrations promoted larger spheroids in classical subtype cells, while basal-like cells required increased collagen for self-organization into compacted, smaller spheroids. These cell line-specific differences were also evident when HPSCs were integrated into the 3D culture to examine tumour-stroma interactions. HPSCs had opposing effects on classical cell lines: one cell line exhibited enhanced spheroid growth, while another showed inhibited spheroid formation, whereas basal-like spheroids were minimally affected. These findings emphasized the importance of the cell-specific and stromal-dependent factors in PDAC progression. Beyond tumour growth and 3D organisation, we explored the role of the TME in aberrant tumour glycosylation, a fundamental post-translational modification that influences tumour progression, immune evasion and metastasis. Our results revealed that both HPSCs interactions and the inherent 3D tumour architecture altered glycosylation patterns, particularly sialylation, fucosylation, Tn antigen and N-/O-glycan expression. Many of these modifications were absent in traditional two-dimensional (2D) cultures, reinforcing the need for improved in in vitro culture models to better capture PDAC complexity. Ultimately, this work has underscored the necessity of complex 3D models to better reflect the biological and mechanical landscape of PDAC and improve diagnostic and therapeutic intervention strategies. By integrating key TME features, we have presented a versatile 3D culture model that lays the groundwork for understanding how specific TME components drive essential PDAC processes. This system has offered valuable insights into how ECM properties and stromal interactions influence tumour behaviour, while also serving as a tool for drug screening, personalised medicine, and the development of stroma-targeted therapies.<br /
Palabras que cuidan: una propuesta formativa en comunicación compasiva en contextos de vulnerabilidad
Get PDFOverall Equipment Effectiveness for Elevators (OEEE) in Industry 4.0: Conceptual Framework and Indicators
Get PDFIn the context of Industry 4.0 and the proliferation of smart buildings, elevators represent critical assets whose performance is often inadequately measured by traditional indicators that overlook energy consumption. This study addresses the need for a more holistic Key Performance Indicator (KPI) by developing the Overall Equipment Effectiveness for Elevators (OEEE), an index designed to integrate operational effectiveness with energy efficiency. The methodology involves adapting the classical OEE framework through a comprehensive literature review and an analysis of elevator energy standards. This leads to a novel structure that incorporates a dedicated energy efficiency dimension alongside the traditional pillars of availability, performance, and quality. The framework further refines the performance and energy efficiency dimensions, resulting in six distinct sub-indicators that specifically measure operational uptime, speed adherence, electromechanical conversion, fault-free cycles (as a proxy for operational quality), and energy use during both movement and standby modes. The primary result is the complete mathematical formulation of the OEEE, a single, integrated KPI derived from these six metrics and designed for implementation using data from modern IoT-enabled elevators. The study concludes that the OEEE provides a more accurate and comprehensive tool for asset management, enabling data-driven decisions to enhance reliability, optimise energy consumption, and reduce operational costs in smart vertical transportation systems
Unmet Supportive Care Needs in Cancer Survivors in Spain: A Multicentre Cross-Sectional Study on Prevalence and Sociodemographic and Disease-Related Risk Factors
Get PDFThis multicentre study investigates unmet supportive care needs (SCNs) among cancer survivors in Spain and analyses sociodemographic and cancer-related risk factors. Methods: A cross-sectional design was used with 1862 cancer survivors aged 18–92 years who had completed primary treatment with curative intent and were disease-free. Participants responded to the Cancer Survivors’ Unmet Needs (CaSUN) questionnaire. Descriptive and multivariate analyses explored SCNs in the total sample and subgroups, as well as differences according to sociodemographic and cancer-related variables. Results: At least 20% of participants reported 18 needs out of a total of 35 identified by the CaSUN questionnaire. One-third to half reported needs in the comprehensive care and information domain. Risk factors for reporting more needs included younger age; female sex; not having a partner; being on sick leave or unemployed; having a diagnosis of haematological, breast or gynaecological cancer; receiving systemic treatment (chemotherapy and/or hormone therapy); and being at an earlier stage of survival. Conclusions: The study highlights significant unmet care needs among cancer survivors in Spain and the urgency of improving management of the physical and psychosocial effects of cancer and its treatment. Special attention should be given to those at greatest risk through personalised and comprehensive care strategies integrated into survivorship programs
Mycotoxin Research in Algeria: A Comprehensive Review of Trends, Challenges, and Future Directions
Get PDFThis review offers a comprehensive overview of mycotoxin research and related publications in Algeria, outlining key trends, existing challenges, and prospects for future advancement. Despite limited exploration of mycotoxins in Algeria, researchers have made significant progress in understanding mycotoxin contamination and its effects on food safety and public health. The review delves into both research achievements and the challenges encountered in resource-limited settings, while also exploring strategies employed to surmount these obstacles. Through an analysis of existing literature, key themes emerge regarding mycotoxin identification, detection methods, mitigation strategies, and their implications. The importance of collaborative efforts among academia and government agencies is underscored as pivotal in addressing mycotoxin-related challenges. Moreover, this review identified gaps in current research and offered recommendations for future investigations, aiming to advance mycotoxin research in Algeria and beyond