Search

Resumen: Objetivo: Describir la financiación pública a proyectos de investigación sobre salud LGTBIQ + en España. Método: Se realizó un estudio cuantitativo observacional de alcance descriptivo. Se revisaron los proyectos concedidos en la convocatoria pública de Proyectos de Investigación en Salud del Instituto de Salud Carlos III entre 2013 y 2019. Se consultó el portal del Fondo de Investigación en Salud para identificar los proyectos de salud financiados que incluían, total o parcialmente, al colectivo LGTBIQ + . Se calcularon las frecuencias absolutas y relativas de los proyectos LGTBIQ + sobre el total de los proyectos financiados, así como los porcentajes por año de concesión, tema, población específica LGTBIQ + y financiación recibida. Resultados: Solo el 0,4% (n = 16) de los 4404 proyectos financiados y el 0,3% del presupuesto otorgado en la convocatoria incluyeron total o parcialmente al colectivo LGTBIQ + . Los proyectos LGTBIQ + se centraban mayoritariamente en hombres que tienen sexo con hombres (n = 14) y en el virus de la inmunodeficiencia humana (VIH) (n = 11). El número de proyectos LGTBIQ + financiados disminuyó entre 2013 (n = 6) y 2019 (n = 0). Conclusiones: En España, los proyectos de investigación sobre salud LGTBIQ + financiados con fondos públicos son escasos. Los pocos estudios financiados se centran en hombres y en el VIH, por lo que no se genera suficiente conocimiento sobre otros temas o poblaciones específicas. Es necesario fomentar la investigación en salud de las personas LGTBIQ + para mitigar las inequidades en salud, ofrecer servicios de salud inclusivos y mejorar la salud de tres millones de personas LGTBIQ + residentes en España. Abstract: Objective: To describe the public funding of research on LGTBIQ + health in Spain. Method: We conducted an observational and descriptive study. We sought research projects dealing with LGTBIQ + health funded by the research projects grant from the Instituto Carlos III from 2013 to 2019. We consulted the webpage and the FIS portal and we identified projects that included LGTB community, totally or partially. We estimated the absolute and relative frequencies of LGTBIQ + projects in relation to total funded projects; and we described the LGTBIQ + funded projects by year of funding, topics, LGTBIQ + subpopulation, or funding. Results: Only 0,4% (n = 16) of 4404 funded projects included —totally or partially— LGTBIQ + community, which represents only 0,3% of the funding. LGTBIQ + projects mainly focused on men who have sex with men (n = 14) and the human immunodeficiency viruses (HIV) (n = 11). The number of funded LGTBIQ + projects decreased from 2013 (n = 6) to 2019 (n = 0). Conclusions: Research projects on LGTBIQ + health are scarce in Spain. Current funding for research on LGTBIQ + health is insufficient to care for population other than HIV and men within LGTBIQ + . There is a compelling necessity to promote the LGTBIQ + health research to mitigate health disparities, to offer inclusive health services, and to improve healthcare of about 3 million LGTBIQ + people living in Spain.

La Teoría de los Conjuntos Aproximados (RST) abrió una nueva dirección en el desarrollo de teorías sobre la información incompleta y es una poderosa herramienta para el análisis de datos. En esta investigación se demuestra la posibilidad de usar esta teoría para generar conocimiento a priori sobre un conjunto de datos. Se desarrolla una propuesta para caracterizar a priori conjuntos de entrenamiento, usando medidas de estimación de la RST. La propuesta ha sido estudiada experimentalmente usando bases de datos internacionales y se han obtenido resultados satisfactorios.

Objetivos: Entre los profesionales sanitarios se han hallado altos índices de desgaste profesional. Nuestro objetivo fue estudiar la prevalencia del síndrome de desgaste profesional en los trabajadores sanitarios hospitalarios, y valorar su relación con los factores personales y ambientales. Métodos: Un total de 2.290 trabajadores sanitarios de 5 hospitales de Girona fueron invitados a participar. Se les administró un cuestionario de elaboración propia, una encuesta del clima organizacional, y el Maslach Burnout Inventory, que incluye tres dimensiones: cansancio emocional, despersonalización y baja realización personal. Resultados: Contestaron la encuesta 1.095 trabajadores (con un 47,8% de participación). Un 41,6% presentó un alto nivel de cansancio emocional, sobre todo los médicos y el personal de enfermería; un 23% tuvo un alto nivel de despersonalización, sobre todo los médicos, y un 27,9% tuvo una baja realización personal, en especial los técnicos y los médicos. Mediante un análisis de regresión logística múltiple, se asoció un alto nivel de cansancio emocional al consumo de tranquilizantes o antidepresivos con asiduidad, mientras que el optimismo y la satisfacción profesional mostraron una asociación inversa. Los años de profesión, el optimismo, valorar como útil el trabajo y percibir que se es valorado por los demás se asociaron inversamente con un alto nivel de despersonalización. La baja realización personal se asoció inversamente con el optimismo, la valoración de la utilidad del trabajo y el equipo de trabajo. Conclusiones: A partir de los resultados obtenidos, recomendamos mejorar el clima organizacional y potenciar el optimismo y la autoestima individual, para disminuir el desgaste profesional en los hospitales.Objectives: High rates of professional burnout syndrome have been found among health service professionals. Our objective was to study the prevalence of burnout syndrome in hospital health workers and to determine its relationship with personal and environmental factors. Methods: A total of 2290 health workers from five hospitals in the province of Girona (Spain) were invited to participate. Interviewees were given a specifically designed questionnaire, a questionnaire on organizational climate, and the Spanish version of the Maslach Burnout Inventory, which includes three scales: emotional exhaustion, depersonalization, and reduced personal accomplishment. Results: Responses were received from 1095 health workers (a response rate of 47.8%). A high level of emotional exhaustion was found in 41.6% of staff members, especially among doctors and nurses; a high level of depersonalization was found in 23%, mainly among doctors, and reduced personal accomplishment was found in 27.9%, mainly among technicians and doctors. Multiple logistic regression revealed that a high level of emotional exhaustion was associated with frequent consumption of tranquilizers or antidepressants, whereas optimism and job satisfaction showed an inverse association. The variables that were inversely associated with a high level of depersonalization were the number of years in the profession, optimism, evaluation of work as being useful and the perception of being valued by others. Reduced personal accomplishment was also inversely associated with optimism, satisfaction with the usefulness of one's work, and satisfaction with teamwork. Conclusions: In view of the results obtained, to reduce professional burnout in hospitals, optimism and a sense of self-worth among individuals should be encouraged and the organizational environment should be improved.

En este trabajo se investiga acerca de las técnicas del soft computing y sus potencialidades en el aprendizaje automático y la clasificación. Se presenta un nuevo algoritmo MLRul que permite aprender y generalizar en forma de reglas borrosas del tipo Sugeno grado cero el conocimiento implícito en bases de casos. Para la prueba del algoritmo se presenta el sistema MLClassif version 1.0 que implementa el algoritmo y un módulo que posibilita la explotación de la base de reglas generadas por MLRul. Se comparan los resultados experimentales de aplicar MLClassif con reglas generadas por MLRul con otros sistemas clasificadores sobre bases de datos publicadas en el repositorio de aprendizaje automático de la Universidad de California Irvine.

Los Sistemas de Enseñanza-Aprendizaje Inteligentes son programas que portan conocimientos de cierto contenido mediante un proceso interactivo individualizado. En este trabajo se expone un modelo que integra el paradigma del Razonamiento Basado en Casos y los Sistemas de Enseñanza-Aprendizaje Inteligentes que favorece la concepción de estos sistemas a usuarios no expertos en informática, teniendo en cuenta las facilidades y naturalidad del enfoque basado en casos. Abstract The Intelligent Teaching-Learning Systems are programs which carry knowledge about certain subject through an individualized interactive process. In the present work, a model which integrates the case-based reasoning paradigm and the Intelligent Teaching-Learning Systems is proposed, the model favors the design of these systems by users no necessarily experts in the informatics field, taking into account the facilities and naturalness of the case-based approach.

No hay resumen

Abstract Clathrin forms a triskelion, or three-legged, network that regulates cellular processes by facilitating cargo internalization and trafficking in eukaryotes. Its N-terminal domain is crucial for interacting with adaptor proteins, which link clathrin to the membrane and engage with specific cargo. The N-terminal domain contains up to four adaptor-binding sites, though their role in preferential occupancy by adaptor proteins remains unclear. In this study, we examine the binding hierarchy of adaptors for clathrin, using integrative biophysical and structural approaches, along with in vivo functional experiments. We find that yeast epsin Ent5 has the highest affinity for clathrin, highlighting its key role in cellular trafficking. Epsins Ent1 and Ent2, crucial for endocytosis but thought to have redundant functions, show distinct binding patterns. Ent1 exhibits stronger interactions with clathrin than Ent2, suggesting a functional divergence toward actin binding. These results offer molecular insights into adaptor protein selectivity, suggesting they competitively bind clathrin while also targeting three different clathrin sites.

During meiotic prophase I, tightly regulated processes take place, from pairing and synapsis of homologous chromosomes to recombination, which are essential for the generation of genetically variable haploid gametes. These processes have canonical meiotic features conserved across different phylogenetic groups. However, the dynamics of meiotic prophase I in non-mammalian vertebrates are poorly known. Here, we compare four species from Sauropsida to understand the regulation of meiotic prophase I in reptiles: the Australian central bearded dragon (Pogona vitticeps), two geckos (Paroedura picta and Coleonyx variegatus) and the painted turtle (Chrysemys picta). We first performed a histological characterization of the spermatogenesis process in both the bearded dragon and the painted turtle. We then analyzed prophase I dynamics, including chromosome pairing, synapsis and the formation of double strand breaks (DSBs). We show that meiosis progression is highly conserved in reptiles with telomeres clustering forming the bouquet, which we propose promotes homologous pairing and synapsis, along with facilitating the early pairing of micro-chromosomes during prophase I (i.e., early zygotene). Moreover, we detected low levels of meiotic DSB formation in all taxa. Our results provide new insights into reptile meiosis.

During clathrin-mediated endocytosis in yeast, endocytic coat adaptors, Sla2 and Ent1, must remain attached to the plasma membrane to transmit force from the actin cytoskeleton required for membrane invagination. Here authors present a cryo-EM structure of a 16-mer complex of the ANTH and ENTH membrane-binding domains from Sla2 and Ent1 bound to PIP2 that constitutes the anchor to the plasma membrane.

Membrane proteins (MPs) constitute a large fraction of the proteome, but exhibit physicochemical characteristics that impose challenges for successful sample production crucial for subsequent biophysical studies. In particular, MPs have to be extracted from the membranes in a stable form. Reconstitution into detergent micelles represents the most common procedure in recovering MPs for subsequent analysis. n-dodecyl-β-D-maltoside (DDM) remains one of the most popular conventional detergents used in production of MPs. Here we characterize the novel DDM analogue 4-trans-(4-trans-propylcyclohexyl)-cyclohexyl α-maltoside (t-PCCαM), possessing a substantially lower critical micelle concentration (CMC) than the parental compound that represents an attractive feature when handling MPs. Using three different types of MPs of human and prokaryotic origin, i.e., a channel, a primary and a secondary active transporter, expressed in yeast and bacterial host systems, respectively, we investigate the performance of t-PCCαM in solubilization and affinity purification together with its capacity to preserve native fold and activity. Strikingly, t-PCCαM displays favorable behavior in extracting and stabilizing the three selected targets. Importantly, t-PCCαM promoted extraction of properly folded protein, enhanced thermostability and provided negatively-stained electron microscopy samples of promising quality. All-in-all, t-PCCαM emerges as competitive surfactant applicable to a broad portfolio of challenging MPs for downstream structure-function analysis.

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site.

Adapter proteins assist clathrin coated pit assembly. Here, the authors combine native mass spectrometry, crystallography and SAXS measurements and show that the membrane–proximal domains of the adaptor proteins epsin and Sla2 form complexes mediated through phosphatidylinositol 4,5-bisphosphate interfaces leading to assembly formation.

Objetivo: Caracterizar el ausentismo laboral por enfermedad de origen infeccioso en una Institución Forense de la Ciudad de Cali (Colombia). Metodología: Estudio descriptivo, de corte transversal realizado una base de datos de 179 incapacidades médicas por enfermedad infecciosa en una institución forense de la ciudad de Cali, Colombia durante los años 2011 y 2012. Se determinaron variables sociodemográficas y laborales como: edad, sexo, escolaridad, oficio, cargo, antigüedad laboral, jornada laboral, tiempo de incapacidad y área laboral. Las incapacidades se clasificaron en menor e igual a 3 días y mayor a 3 días. Las enfermedades infecciosas se clasificaron por sistemas: respiratorias, gastrointestinales, de piel y otras. Resultados: Más de la mitad (50,6%) de la población estudiada presento ausentismo laboral por enfermedades de origen infeccioso. La mayoría (58%) fueron por enfermedades de origen respiratorio. Las mujeres presentaron mayor ausentismo (56%) y el oficio forense presento la mayor prevalencia de ausentismo (73%). El área de patología presento el mayor ausentismo con un 23%. Se encontró una relación significativa entre la edad y el ausentismo por enfermedad de origen infeccioso. Conclusiones: El personal de la Institución Forense está altamente afectado por enfermedades infecciosas de tipo respiratorio y gastrointestinal generando alto volumen de incapacidades.

Background: "Real-life" data on cardiovascular management and clinical outcomes in patients with atrial fibrillation (AF) and hematologic malignancies are limited., Aim: To describe the clinical profile and incidence of cardiovascular events in this population., Methods: Data were obtained from the CANAC-FA Registry, an observational, multicenter and retrospective study. A review of the medical records of patients who had consulted for chronic lymphocytic leukemia (CLL) or multiple myeloma (MM) between 2017 and 2019 was conducted in five hospitals in Spain. Patients with atrial fibrillation (AF) were identified, and the initial visit during which specific treatment for the neoplasm was administered was considered the baseline visit. The follow-up period concluded in 2021. Events of interest included major bleeding, cardiovascular events (hospital admission for cardiovascular causes or cardiovascular death), and death from any cause., Results: A total of 7,793 patients were reviewed, of whom 1,189 (15%) had AF and 81 (1%) had AF and had initiated a specific hematological treatment within the previous year. Of these patients, 48 (59%) had MM and 33 (41%) had CLL. The mean values for the Charlson, CHA2DS2-VASc and HAS-BLED indices were 5.3 ± 1.7, 3.4 ± 1.5 and 2.4 ± 1.1, respectively. Anticoagulants were prescribed to 85% of patients, with a majority (42%) receiving direct anticoagulants. After a maximum follow-up period of 59 months, the incidences of events at 1, 2 and 3 years of follow-up were: 1.2±1.2%, 1.2±1.2 and 3.5±2.5% for major bleeding; 11.6±3.7%, 11.6±3.7 and 17.2±5.3% for cardiovascular events; and 27.6±5.0%, 41.5±6.3 and 51.3±6.9% for all-cause mortality., Conclusions: The incidence of cardiovascular events was high in this population, suggesting the need to implement more effective preventive strategies., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To analyze clinical characteristics of non-anticoagulated subjects with major bleeding, and to determine the incidence of adverse events, healthcare resource utilization (HCRU) and associated costs following a major bleeding event. Methods : Retrospective observational cohort study that analyzed secondary data from electronic health records in Spain. Non-anticoagulated patients with a first major bleeding during the study period (between January 2013 and December 2022) were analyzed for 3 years. Results : A total of 4089 patients (mean age 57.26 (12.87) years, 58.47% female) were included. A proportion of 27.63% presented with genitourinary bleeding, 22.43% with gastrointestinal bleeding, 5.16% with respiratory bleeding and 3.11% with intracranial hemorrhage. At the end of the first major bleeding event, 0.56% of patients died (5.51% after intracranial hemorrhage, 3.23% in case of trauma-related bleeding). The incidence rates of clinical outcomes per 100 person-years within the first 3 months of the major bleeding were death from any cause 7.51 (95% CI 6.70-8.32), cardiovascular death 1.80 (95% CI 1.39-2.21), acute myocardial infarction 4.53 (95% CI 3.89-5.17), and ischemic stroke 3.52 (95% CI 2.96-4.08), and decreased over time. At year 3, mean overall major bleeding cost per patient was EUR 13,310.00 (5153.05), of which EUR 7648.20 (2674.46) (57.46%) accounted for in-hospital costs to treat the major bleeding event. Conclusions : Among non-anticoagulated patients presenting with a first major bleeding, <1% of patients died during index hospitalization. However, these patients had a substantial risk of adverse clinical events during the follow-up, as well as high associated HCRU and costs.

Introduction: To analyze the role of perforating scleral vessel (PSV) and dilated choroidal veins (DCV) underneath macular myopic choroidal neovascularization (mCNV)., Methods: This retrospective case-control study analyzed 78 eyes from 78 highly myopic patients defined by an axial length (AL) of ≥26 mm, assessed by optical coherence tomography (OCT) and OCT-angiography (OCTA) imaging. Patients with clinical diagnosis of mCNV and good-quality OCTA images were selected. Swept source (SS)-OCT and SS-OCTA images (TRITON; Topcon Corporation, Tokyo, Japan) were reviewed to detect image markers in the mCNV area. Highly myopic eyes without mCNV, matched by age and AL, were used as control group. The presence of PSV and DCV were recorded. Myopic maculopathy was graded using the ATN (Atrophic, Traction and Neovacularization) classification., Results: 78 eyes from 78 patients (39 with mCNV and 39 without mCNV) were included, out of the total 775 eyes screened. Fifty-nine (75.6%) of them were women. The mean ATN grading of myopic-maculopathy was compared between eyes with mCNV and those without mCNV: Atrophy scores were 2.71±0.97 vs. 2.30±0.89, respectively (p=0.04); Traction scores were 0.64±0.66 vs. 0.84±0.98, respectively (p=0.54); and Neovascularization scores were 2.00±0.00 vs. 0.33±0.73, respectively (p<0.001). The presence of OCT-imaging markers did not significantly differ between groups; i.e., PSV was found in 34/39 vs. 32/39 (p=0.53) eyes and DCV was found in 11/39 vs. 7/39 eyes, mCNV vs. control group respectively (p=0.28)., Conclusions: PSV and DCV are image markers present in a high number of highly myopic eyes, which are not specific to mCNV., (S. Karger AG, Basel.)

Background: This study explores the relationship between primary dysmenorrhea (PD), pain, pain catastrophizing, and menstruation-related quality of life in young women., Methods: A cross-sectional study was conducted involving 44 young women, both with and without PD. Various variables including pain intensity, pain catastrophizing, and menstruation-related quality of life were assessed using validated questionnaires. Correlation and regression analyses were performed to examine the relationships between the variables., Results: Significant associations were found between the presence of PD, tendency to catastrophize pain, and decreased menstruation-related quality of life. A high correlation was observed between pain intensity and catastrophizing, indicating mutual influence between these variables. Menstruation-related quality of life was affected in terms of health perception, psychological aspect, and symptoms among women with PD. The linear regression model demonstrated that catastrophizing explained 42.8% of the variance in menstruation-related quality of life., Conclusions: These findings underscore the importance of addressing dysmenorrhea in young women, as it significantly impacts their quality of life related to menstruation. Understanding the factors contributing to dysmenorrhea and its effects on quality of life can inform more effective, patient-centered treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 Del Prado, García-Arrabé, González-de-la-Flor, De La Plaza San Frutos, Almazán Polo, Guérineau and Estrada-Barranco.)

Primary dysmenorrhea (PD) is a common gynecological condition characterized by menstrual pain without underlying pelvic pathology. It has been linked to functional and structural changes in the core musculature, but limited evidence exists regarding its association with diaphragmatic and respiratory mechanics. This study aimed to elaborate on these potential associations by assessing the diaphragmatic structure and respiratory function in women with PD compared to healthy controls, utilizing ultrasound imaging, spirometry and respiratory pressure measurements., Methods: An observational, cross-sectional study was conducted with 44 female participants (22 with PD and 22 healthy controls). Diaphragmatic structure was evaluated through ultrasound, measuring the intercostal distance, diaphragmatic thickness, and diaphragmatic excursion at rest and during maximum voluntary contraction. Spirometric assessments included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the FVC/FEV1 ratio, along with measurements of maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP). Group differences were analyzed using Student's t -test and effect sizes were reported with Cohen's d., Results: No significant differences were observed between the groups in diaphragmatic thickness, diaphragmatic excursion, or global respiratory capacity ( p > 0.05). However, women with PD presented a significant reduction in the left intercostal distance both at rest ( p = 0.035, d = 0.56) and during contraction ( p = 0.039, d = 0.54). No other significant group differences were detected., Conclusions: While primary dysmenorrhea does not appear to affect overall diaphragmatic function or respiratory capacity, it is associated with subtle localized changes in the left intercostal dynamics. These findings suggest a potential compensatory mechanical adaptation rather than global respiratory dysfunction. Further longitudinal studies with larger sample sizes are needed to explore the clinical significance of these findings.

Purpose: To analyze myopic maculopathy's progression pattern., Design: Retrospective, observational case series., Methods: A total of 824 highly myopic eyes (axial length ≥26 mm) of 430 patients examined at Puerta de Hierro-Majadahonda University Hospital (Madrid, Spain) with a minimum follow-up of 2 years. All patients underwent complete ophthalmologic examination, including multimodal imaging. Progression of myopic maculopathy was assessed according to ATN classification system at baseline and throughout the follow-up, as well as associated clinical features., Results: Progression of myopic maculopathy was described in 42% of eyes over a mean follow-up of 4.10 ± 1.28 (range, 2.00-6.23) years. Compared with nonprogressing eyes, myopic maculopathy progression correlated with worse best-corrected visual acuity (BCVA) at follow-up (P < .05) and greater BCVA loss (P < .01). There were no significant differences between groups in axial length, gender, and age (P > .05). Eyes with posterior staphyloma (PS) and, particularly, those with macular PS showed significantly greater myopic maculopathy progression (P < .01). The likelihood of myopic maculopathy's progression was 3.94 times higher (odds ratio, 3.94 ± 1.22, P < .01) in eyes with PS compared with those without PS. Atrophic progression occurred in 21.9% of eyes, with diffuse to patchy atrophy being the most common pattern (54.17%). Tractional progression was observed in 22.8% of eyes, predominantly from nontraction to inner/outer foveoschisis (40%). Neovascular progression affected 11.4% of the eyes, most of them from no neovascular component to macular lacquer cracks (40%)., Conclusions: This study highlights significant myopic maculopathy progression over the natural course of the disease, compromising the BCVA as macular complications progress. Myopic maculopathy progression was significantly associated with PS, especially in those with macular involvement., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval., Method: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit., Results: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia., Conclusion: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background/Objectives : Metabolic syndrome is a significant public health issue, particularly in urbanizing regions like the Peruvian Amazon, where lifestyle changes have increased the prevalence of metabolic disorders. This study aimed to develop and validate a simple, cost-effective diagnostic model for early detection of metabolic syndrome in the urban population of San Juan Bautista, Iquitos. Methods : A cross-sectional study was conducted with 251 adults aged over 18 years. Data collection included anthropometric measurements, body composition analysis, and biochemical assessments. Logistic regression analyses identified key predictors of metabolic syndrome, and clinical decision trees were developed to enhance diagnostic accuracy. Results : The prevalence of metabolic syndrome was 47.9%. Systolic blood pressure, triglycerides, and very-low-density lipoprotein cholesterol were the strongest predictors. The most effective diagnostic model, combining very-low-density lipoprotein cholesterol and systolic blood pressure, achieved a sensitivity of 91.6% and a specificity of 78.5%, demonstrating high diagnostic accuracy. Conclusions : The proposed model offers a practical, low-cost tool for early detection of metabolic syndrome in resource-limited urban settings. However, its findings are limited by the small sample size and the lack of external validation, requiring further studies to confirm its generalizability and applicability to other populations. Its implementation in primary healthcare could facilitate timely interventions, reducing the risk of chronic diseases in vulnerable populations.

Aims: Patients with heart failure (HF) commonly have poor quality of life (QoL), secondary to the persistence and severity of HF symptoms. We aimed to evaluate the prognostic value of QoL measures on all-cause mortality in patients with HF from the Colombian registry of heart failure (RECOLFACA)., Methods and Results: We analysed data from patients registered in RECOLFACA during 2017-19. QoL was measured using the EuroQol-5D questionnaire (EQ-5D). From the questionnaire, two independent predictors of mortality were obtained, the visual analogue scale (VAS) and the utility score (US). The primary outcome was all-cause mortality, and secondary variables evaluated were demographic factors, comorbidities, NYHA classification, medications used, and laboratory test results. To analyse survival among patients, the Kaplan-Meier method and the hierarchical Cox proportional hazards regression model were used. This study included 2514 patients from RECOLFACA. Most patients were male (57.6%), and the mean age was 67.8 years. The mean value and standard deviation (SD) of the VAS score was 78.8 ± 20.1 points, while the mean and SD of the US score was 0.81 ± 0.20. As the Kaplan-Meier curve illustrated, patients in the lower quartiles of both VAS and US scores had a significantly higher probability of mortality (log-rank test: P < 0.001 for both scores)., Conclusion: QoL, as calculated by the EQ-5D questionnaire, served as an independent predictor of mortality in patients from RECOLFACA. Further studies may be needed to evaluate whether the provision of optimizing therapies and follow-up care based on patients' perceived QoL reduces short- and long-term mortality rates in this population., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In acute myeloid leukemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche is unclear. Here, we found that relapsing AML cells increase translation in their bone marrow (BM) niches, where BM mesenchymal stromal cells (BMSCs) become a source of eIF4A-cap-dependent translation machinery that is transferred to AML cells via extracellular vesicles (EVs) to meet their translational demands. In two independent models of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD (internal tandem duplication) and nucleophosmin (NPMc) mutations, protein synthesis levels increase in refractory AML dependent on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, while EVs from BMSCs carrying eIF4A boost AML cell translation and survival. Consequently, eIF4A inhibition synergizes with conventional chemotherapy. Together, these results suggest that AML cells rely on BMSCs to maintain an oncogenic translational program required for relapse., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Achilles tendon is the strongest and largest tendon in the human body, yet it is also the most frequently ruptured. The incidence of Achilles tendon rupture (ATR) is increasing due to an ageing population, rising obesity rates and greater sports participation. The Achilles Tendon Total Rupture Score (ATRS) is a validated patient-reported outcome measure widely used to assess clinical and functional outcomes after ATR. However, there is no culturally adapted and validated Spanish version of this tool, limiting its applicability in Spanish-speaking populations. The aim is to translate, culturally adapt and validate the Spanish version of the ATRS following international guidelines and to analyse its psychometric properties for assessing clinical and functional outcomes in patients with ATR. This study protocol outlines a cross-sectional design adhering to Strengthening the Reporting of Observational Studies in Epidemiology and Checklist for Reporting Results of Internet E-Surveys guidelines for observational studies and online surveys. The ATRS will be translated and culturally adapted, psychometric analysis will follow COnsensus-based Standards for the selection of health Measurement INstruments standards, including reliability, validity and sensitivity assessments. Participants will include patients treated surgically for ATR in hospitals across Madrid and healthy controls recruited through social media. Sociodemographic, clinical and functional data will also be collected to support the validation process. This study protocol was approved by the Universidad Europea de Madrid Institutional Board (Approval ID: CI 2024/897) prior to data collection based one the Declaration of Helsinki. The study's findings will be distributed to athletes, physicians and academics via peer-reviewed publications and national/international conferences., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

A 16-year-old boy was diagnosed from multiple sclerosis (MS) after suffering from paresthesia in upper limbs and VI cranial nerve paresis. Corticosteroids and fingolimod were started. After 13 months a worsening of liver biochemical tests (LBT) was noticed: ALP 787 U/L, GGT 737 U/L, AST 195, ALT 321, Bi 0.5 mg/dL, so fingolimod was stopped. Serologies were negative, thyroid function, Alpha-1-antitrypsin, ceruloplasmin, and iron metabolism tests were normal. He had ANA 1/320 and c-ANCA positive autoantibodies. After 3 months there was no improvement of LBT: ALP 726 AST 87 ALT 95 GGT 515 Bi 0.7. After an elevation of IgG (18,23g/L), a liver biopsy (LB) and a magnetic resonance cholangiography (MRC) were performed, being diagnosed from small duct Primary Sclerosing Cholangitis (PSC). A review of liver biopsy from specialized pathologists was requested, showing changes consistent with overlap autoimmune hepatitis (AIH). Ursodeoxycholic acid was initiated with decrease of AP and GGT. No treatment with corticosteroids or immunosuppressant agents were required since AST/ALT spontaneously decreased. Natalizumab was introduced with adequate control of MS. Autoimmune liver diseases are believed to have a multifactorial but unknown etiology. Studies have reported the coexistence of MS with other autoimmune diseases (AD) 1. Drug toxicity (DILI) is becoming a relatively important cause of liver altered tests given emerging therapies used as disease-modifying agents 2. In comparison to a 0.02% prevalence of AIH in general population, AIH was diagnosed in a cohort of MS in 3 out of 1800 patients (0.17%) 3. Only 1 case of MS and PSC has been reported in 2003 4. Therefore we present the first case of PSC/AIH overlap in a patient with MS so far. The existence of a previous AD in a young patient with chronic and fluctuating LBT alteration lead to the suspicion of an AILD. Some authors believe AIH/PSC-overlap might represent the same entity, described in childhood as `autoimmune sclerosing cholangitis (ASC)', with inflammatory phases of PSC manifesting earlier in the disease course as AIH and developing duct fibrosis over time 5. Treatment of MS with immunosuppressants and biologics agents such as natalizumab, might have influenced the decrease in serum transaminases due to their role in blocking leukocyte migration, which might also affect immune response in the liver.

Enhancers are short DNA sequences that activate their target promoter from a distance; however, increasing the genomic distance between the enhancer and the promoter decreases expression levels. Many genes are controlled by combinations of multiple enhancers, yet the interaction and cooperation of individual enhancer elements are not well understood. Here, we developed a synthetic platform in mouse embryonic stem cells that allows building complex regulatory landscapes from the bottom up. We tested the system by integrating individual enhancers at different distances and confirmed that the strength of an enhancer contributes to how strongly it is affected by increased genomic distance. Furthermore, synergy between two enhancer elements depends on the distance at which the two elements are integrated: introducing a weak enhancer between a strong enhancer and the promoter strongly increases reporter gene expression, allowing enhancers to activate from increased genomic distances., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the transfer effects of a home-based computerized executive function intervention on non-targeted cognitive functions (visual perception and memory), quality of life (QoL), and participation in children with cerebral palsy (CP), and to determine whether any improvements were maintained 9 months after the intervention., Method: Sixty children with CP (aged 8-12 years) were randomly allocated to the intervention (15 females/15 males, mean age 10 years 4 months [SD = 1 years 8 months], age range 8-12 years) or waitlist (control) (15 females/15 males, mean age 10 years [SD = 1 years 9 months], age range 8-12 years) group. The intervention group underwent a home-based executive function intervention programme for 30 minutes per day, 5 days a week, for 12 weeks. All participants were assessed before the intervention, immediately after and 9 months after the intervention was completed., Results: After the intervention was completed, performance in immediate verbal memory, verbal learning, and visual perception (object and picture recognition) was significantly better in the intervention group than in the waitlist (control) group. No improvements were found in visual memory, visuospatial perception, QoL, or participation after the intervention. Scores at the follow-up showed that any beneficial effects were not maintained 9 months after the intervention was completed., Interpretation: A home-based computerized executive function intervention produced transfer effects on memory and visual perception immediately after the intervention in children with CP, although any beneficial effects were not sustained at the 9-month follow-up., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: The advent of Alzheimer's disease-modifying drugs requires accurate biological diagnosis to identify candidates for these therapies. So far, the most promising single plasma biomarker is phosphorylated tau at threonine 217 (p-tau217). To understand its biological features, it is essential to know its longitudinal trajectory and factors influencing it in cognitively unimpaired subjects with no brain pathology., Methods: We analyzed longitudinal plasma p-tau217 values (mean follow-up time = 768.3 days) in a cohort of 209 healthy volunteers. We have studied factors associated with plasma p-tau217 changes by using different linear mixed-effects models., Results: In amyloid-negative cognitively healthy subjects (n = 151) carriers of ApoE ε4 allele had significantly higher p-tau217 values than non-carriers (0.85 pg/mL; p-value < 0.001) and also a greater rate of change (0.01 pg/mL/year; p-value < 0.001). In the overall sample, including subjects with amyloid and tau pathology we have seen that amyloid positive subjects had higher predicted baseline plasma p-tau217 values than amyloid negative subjects (0.16 pg/mL; p-value < 0.001) and a greater rate of change (0.00004 pg/mL/day; p-value < 0.001). Subjects considered tau positive also showed a greater rate of change of p-tau217 with respect to tau negative (0.00005 pg/mL/day; p-value < 0.001). A + T + N + participants showed a higher baseline p-tau217 levels than A-T-N- subjects (0.2 pg/mL; p-value < 0.001) and also a greater rate of change (0.00006 pg/mL/day; p-value = 0.002). ApoE ε4 carriers had a greater rate of change than non-carriers (0.00003 pg/mL/day; p-value = 0.03)., Conclusion: In amyloid-negative cognitively unimpaired subjects, ApoE4 status influenced both baseline levels and rate of change of plasma p-tau217. Other factors such as age, sex or glomerular filtration rate have not shown significant influence on plasma p-tau217 levels in this group., Competing Interests: Declarations. Ethics approval and consent to participate: This research has been conducted in accordance with the Declaration of Helsinki and has been approved by the ethics committee of the Hospital Universitario Marqués de Valdecilla. Title: Valdecilla Cohort for the study of memory and brain aging. Internal code: 2018.111. All subjects have given their signed consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Therapy resistance in human cancers is a major limitation in Clinical Oncology. In this regard, overexpression of anti-apoptotic proteins, such as survivin, has been described in several tumors, contributing to this clinical issue. Survivin has a dual role in key cellular functions, inducing cell cycle progression and inhibiting apoptosis; thus, survivin is an attractive target for cancer therapy. Therefore, we focused on identifying and validating a novel specific, directly binding survivin inhibitor for cancer treatment and tumor sensitization to conventional proapoptotic therapies. In this work, we conducted a structure-based high-throughput virtual screening at the survivin homodimerization domain. Asenapine Maleate (AM), an approved drug for central nervous system diseases, was identified as a direct binder of the survivin homodimerization domain and it significantly affected cell viability of lung, colon, and brain cancer cell lines. Direct interaction of AM to survivin protein was corroborated by surface plasmon resonance and a specific survivin protein decrease was observed in cancer cells, compared to other inhibitors of apoptosis proteins. Therapeutic in vivo studies showed an impairment of tumor growth in AM-treated mice. Finally, a synergistic anticancer effect was detected in vitro when combined with different conventional chemotherapies, and in vivo studies showed higher antitumor effects when combined with cisplatin. Altogether, our results identify AM as a specific direct binding inhibitor of survivin, showing anticancer properties in vitro and in vivo and sensitizing effects when combined with cisplatin, opening the possibility of repositioning this approved drug for cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper Vanessa Soto-Cerrato and other co-authors had patent #PCT/EP2022/071374 pending to none (no longer in force). Co-author currently employed by Nostrum Biodiscovery (as mentioned in her affiliation): LD Co-author previously employed by Nostrum Biodiscovery (as mentioned in her/his affiliation): YW, RS. Therefore, there are no conflict of interests. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background/Objectives : Pathophysiological variability in patients with cancer is associated with differences in responses to pharmacotherapy. In this work, we aimed to describe the demographic characteristics and hematological, biochemical, and coagulation variables in a large oncology cohort and to develop, optimize, and provide open access to modeling equations for the estimation of variables potentially relevant in pharmacokinetic modeling. Methods : Using data from 1793 patients with cancer, divided into training ( n = 1259) and validation ( n = 534) datasets, a modeling network was developed and used to simulate virtual oncology populations. All analyses were conducted in RStudio 4.3.2 Build 494. Results : The simulation network based on sex, age, biogeographic origin/ethnicity, and tumor type (fixed or primary factors) was successfully validated, able to predict age, height, weight, alpha-1-acid glycoprotein, albumin, hemoglobin, C-reactive protein and lactate dehydrogenase serum levels, platelet-lymphocyte and neutrophil-lymphocyte ratios, and hematocrit. This network was then successfully extrapolated to simulate the laboratory variables of eight oncology populations ( n = 1200); only East Asians, Sub-Saharan Africans, Europeans, only males, females, patients with an ECOG performance status equal to 2, and only patients with pancreas cancer or ovarian cancer. Conclusions : this network constitutes a valuable tool to predict relevant characteristics/variables of patients with cancer, which may be useful in the evaluation and prediction of pharmacokinetics in virtual oncology populations, as well as for model-based optimization of oncology treatments.

Background: Primary Health Care (PHC) plays a pivotal role in the healthcare system as the initial point of contact for users and patients. In the healthcare area, claims are presented and managed through a web app. It also enables systematic analysis of emerging information to drive continuous improvement. The present objective was to describe the complaints filed at PHC in 2022., Methods: A cross-sectional study was conducted, examining complaints filed by patients in 2022. For inclusion of the complaints, it was established that it had to do with the treatment received by healthcare personnel and that was presented through the web app. Complaint texts signaling dissatisfaction with the information received were subjected to qualitative coding., Results: The study involved 326 users who submitted a total of 358 complaints specifically related to treatment and information. The average age of the participants was 33.5 ± 16.2 years, and the majority were women (72.4 %, n = 236). In 2022, the Cumulative Incidence (CCI) was 55.2 complaints per 100,000 healthcare act and the Complaint Incidence Rate (CIR), defined as the number of complaints/1000 users/year, was 6.5. The prevalence of complaints related to information was 12.4 %. The main reasons for complaints about information were issues related to communication with the patient (79 %), followed by the patient's disagreement with the techniques applied by healthcare staff (17 %)., Conclusions: Results show us the fundamental characteristics of complaints in primary care with respect to the information received by health professionals, not allowing us to know where the authors can influence through interventions or training actions to try to improve., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

The aims of the study are to analyze the influence of pain and no pain expectations on the physiological (electromyography (EMG) and pupillometry) and cognitive (Numerical Rating Scale (NRS)) response to pain. Pain expectation and no pain expectation situations were induced by employing instructional videos. The induction of pain was performed by palpating the masseter with an algometer in a sample of 2 groups: 30 healthy participants (control group) and 30 patients (Temporomandibular disorders (TMD) group) with chronic myofascial pain with referral in the masseter muscle (Diagnostic Criteria for Temporomandibular Dissorders (DC/TMD)). Used a mixed design all participants were exposed to pain and no pain conditions in the same session, but the order of the presentation was counterbalanced across participants to control its possible influence. A significantly larger pupillary diameter was observed in the pain expectation relative to the no pain expectation condition in both groups. The TMD group presented larger EMG activity and larger scores in anxiety, somatization, catastrophizing and central sensitization than the control group. In the NRS, the TMD group also showed a significantly higher score than the control group. The TMD group presented similar NRS scores in the expectation condition compared to the no pain expectation condition, while the control group presented higher scores for pain expectation than for no pain expectation. Pain expectation modulated the pain cognitive pain assessment and pupil diameter in controls. The cognitive pain assessment was altered in the TMD group compared to the control group, particularly in the no pain expectation condition, this may be due to a negative reappraisal of pain due to past experiences, as pointed out by the observed level of catastrophizing. Pain expectations did not influence the EMG, significantly higher EMG activity was found in the TMD group compared to the control group regardless of expectation type., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Background: Iron deficiency is the top leading cause of anaemia, whose treatment has been shown to deteriorate gut health. However, a comprehensive analysis of the intestinal barrier and the gut microbiome during iron deficiency anemia (IDA) has not been performed to date. This study aims to delve further into the analysis of these two aspects, which will mean a step forward minimising the negative impact of iron supplements on intestinal health., Methods: IDA was experimentally induced in an animal model. Shotgun sequencing was used to analyse the gut microbiome in the colonic region, while the intestinal barrier was studied through histological analyses, mRNA sequencing (RNA-Seq), qPCR and immunofluorescence assays. Determinations of lipopolysaccharide (LPS) and bacteria-specific immunoglobulins were performed to assess microbial translocation., Results: Microbial metabolism in the colon shifted towards an increased production of certain amino acids, short chain fatty acids and nucleotides, with Clostridium species being enriched during IDA. Structural alterations of the colonic epithelium were shown by histological analysis. RNA-Seq revealed a downregulation of extracellular matrix-associated genes and proteins and an overall underdeveloped epithelium. Increased levels of serum LPS and an increased immune response against dysbiotic bacteria support an impairment in the integrity of the gut barrier during IDA., Conclusions: IDA negatively impacts the gut microbiome and the intestinal barrier, triggering an increased microbial translocation. This study emphasizes the deterioration of gut health during IDA and the fact that it should be addressed when treating the disease., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Malnutrition and sarcopenia are highly prevalent in patients with head neck cancer (HNC). An accurate early diagnosis is necessary for starting nutritional support, as both are clearly associated with clinical outcomes and mortality. We aimed to evaluate the applicability and accuracy of body composition analysis using electrical bioimpedance vectorial analysis (BIVA) for diagnosing malnutrition and sarcopenia in patients with HNC cancer undergoing systemic treatment with chemotherapy or radiotherapy., Methods: Cross-sectional, observational study that included 509 HNC patients. A comprehensive nutritional evaluation that included BIVA was performed., Results: The prevalence of malnutrition was higher in patients that received treatment with chemotherapy (59.2% vs. 40.8%, P < 0.001); increased mortality was observed in malnourished patients (33.3% vs. 20.1%; P < 0.001); ECOG status (1-4) was also worse in malnourished patients (59.2% vs. 22.8% P < 0.001). Body cell mass (BCM) and fat mass were the most significantly associated parameters with malnutrition [OR 0.88 (0.84-0.93) and 0.98 (0.95-1.01), respectively]; BCM and fat free mass index (FFMI) were associated with several aspects including (1) the patient-generated subjective global assessment [OR 0.93 (0.84-0.98) and 0.86 (0.76-0.97), respectively], (2) the presence of sarcopenia [OR 0.81 (0.76-0.87) and 0.78 (0.66-0.92), respectively]. A BCM index (BCMI) < 7.8 in combination with other parameters including FFMI and BCM accurately predicted patients with malnutrition [accuracy 95% CI: 0.803 (0.763-0.839); kappa index: 0.486; AUC: 0.618 (P < 0.01)]. A BCMI cutoff of 7.6 was enough for identifying males with malnutrition (P < 0.001), while it should be combined with other parameters in females., Conclusions: Body composition parameters determined by BIVA accurately identify patients with HNC and malnutrition. Phase angle, but other parameters including BCMI, FFMI and BCM provide significant information about nutritional status in patients with HNC., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible., Aims: to assess the management of antiTNF-IP in IBD, and its impact in both diseases., Methods: patients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks., Results: 234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse., Conclusion: skin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies., Competing Interests: Conflict of interest DCD is partially supported by a Rio-Hortega fellowship from Instituto de Salud Carlos III. IM reports grants and personal fees from MSD, Janssen, Takeda, Kern and Chiesi, during the conduct of the study. AFC has served as a speaker, or has received education funding from Dr. Falk, Janssen, Takeda, Chiesi and Pfizer. MJG has received financial support for travelling and educational activities from Janssen, Pfizer, AbbVie, Takeda, Kern Pharma, Faes Farma and Ferring. IG has served as speaker or has received education funding from Takeda and Tillots. JPG has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. XC reports grants or contracts from Abbvie, Janssen, Kern, Takeda, Galapagos, Lilly, Sandoz; consulting fees from Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AbbVie, Janssen, Takeda, Galapagos, Kern; participation on a Data Safety Monitoring Board or Advisory Board: X Jansen, Galapagos; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Past-president, Societat Catalana de Digestologia. BG has served as advisor to Galapagos and Abbvie and as speaker for Abbvie, Jansen, Takeda, Pfizer and Galapagos. REM reports grants and personal fees from Janssen, Pfizer and Ferring. NP has served as speaker, consultant and advisory board of has received research funding from MSD, Abbvie, Janssen, Takeda, Roche, Sandoz, Ferring, Adacyte, Faes Farma, Kern Pharma, Pfizer, Shire Pharmaceuticals, Vifor Pharma, Chiesi and Tillots. SGL has served as a speaker, advisory member for or has received research funding from AbbVie, MSD, Takeda, Janssen and Pfizer., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives : The purpose of this study was to determine the association between oral lichen planus (OLP) and the history of cancer outside of oral cavity and the predominance of its location. Methods : This case-control study included 600 OLP patients and 600 control subjects evaluated in the same section, matched for age and sex to the OLP patients. OLP patients were diagnosed clinically and histologically. Initially, the prevalence of the most frequent types of cancers was described. A Pearson chi-squared test model was used to determine the association of cancer history and OLP. It was considered statistically significant whether p value was ≤0.05. The final multivariate regression model was built after applying a backward selection method to the complete multivariate model considering the odds ratio (OR) with a 95% confidence interval (CI). Results : The history of cancer was significantly associated with OLP regardless of age, sex, tobacco and or alcohol use in both univariate [OR = 2.26 (95%CI: 1.26-4.24); p = 0.008] and multivariate analyses [OR = 2.21 (95%CI: 1.21-4.19); p = 0.012]. According to the location of cancer, there was an association between OLP and history of breast cancer [OR = 3.71 (95%CI = 1.03-13.38); p = 0.032]. Conclusions : This case-control study suggests a higher frequency of cancer, particularly breast cancer, among patients with OLP compared to the control group. Due to the study's design and sample limitations, these findings should be interpreted cautiously. Future longitudinal, multi-institutional studies with rigorous control for cancer history and other confounding factors are essential to further explore the association between OLP and cancer, particularly breast cancer.

Primary dysmenorrhea (PD), a prevalent menstrual condition characterized by pelvic pain during the menstrual cycle, significantly impacts the quality of life of women and produces increased pain sensitivity that can persist throughout the menstrual cycle. However, scientific literature has not studied whether there are implications for alterations in muscle function and endurance in the abdominopelvic region during the non-painful phases of the menstrual cycle. The aim of this study was to compare muscle function and endurance capacity in the abdominopelvic region in women with PD versus women without this condition. An observational, cross-sectional study was designed to analyze muscle activation and endurance capacity using electromyography (EMG) during McGill exercises. Forty-four women were included, 22 with PD and 22 without dysmenorrhea. The results did not indicate significant differences in muscle activation and endurance of the abdominopelvic musculature between the two groups (p > 0.05). However, the analysis suggests that women with primary dysmenorrhea might develop compensatory strategies that allow them to maintain physical function despite their condition. These results suggest that the approach to PD could focus more on pain management rather than physical functionality, and more studies are needed from a comprehensive approach to more accurately evaluate the relationship between PD and muscle function., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Commission of Universidad Europea de Madrid (protocol code CIPI/23.146; date of approval: April 20, 2023). Informed consent: Informed consent was obtained from all participants involved in the study., (© 2024. The Author(s).)

The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch-based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM.

The main weakness of non-silicone hydrogel contact lenses is their low oxygen permeability (Dk). Hence, we have tried to optimize their Dk using various concentrations and lengths of the poly (ethylene glycol) dimethacrylate crosslinker in a mixture of N,N-Dimethylacrylamide and Cyclohexyl methacrylate monomers. After synthesizing the different contact lenses, we evaluated their chemical, optical, and mechanical properties. The resultant non-silicone hydrogel contact lenses presented similar high water contents (75.69-80.60%) and adequate optical (e.g., a transmittance ranging from 85.91% to 99.91% and a refractive index between 1.3630 and 1.3740) and elongation at break (178.95-356.05%) characteristics for clinical applications. Conversely, they presented high contact angles (81.00-100.00°) and a low Young's modulus (0.066-0.167 MPa). Regarding the impact of the crosslinking modifications, the water content, contact angle, refractive index, transmittance, and Young's modulus of the synthesized lenses were slightly affected by crosslinker conditions. In contrast, the elongation at break (178.95-356.05%) and, more importantly, the oxygen permeability, which reached values of up to 73.90 Fatt units, were considerably impacted by the crosslinker conditions. To our knowledge, this study demonstrates for the first time that, in addition to water, other usual hydrogel components, like crosslinkers, can modulate the Dk of non-silicone contact lenses. It also provides a simple and scalable method to fabricate more permeable non-silicone lenses.

Background: The purpose of this randomized cross-over controlled trial was to evaluate the biomechanical effects of ankle taping using rigid tape (RT) or kinesiotape (KT) compared to no taping during treadmill running in well-trained amateur runners. Methods : A total of 22 participants (15 men and 7 women) completed three running sessions on a treadmill, each lasting 30 min, under different conditions: no taping (CG), RT, and KT. Sagittal and frontal plane kinematics were analyzed using the Kinovea software to assess the ankle dorsiflexion, knee flexion, hip extension, tibial angle, foot strike pattern, heel eversion, and pelvic drop across three intervals (0-10, 10-20, and 20-30 min). Results : The results demonstrated no significant differences in sagittal plane variables (ankle dorsiflexion, knee flexion, hip extension, and cadence) or frontal plane variables (heel eversion and pelvic drop) between the CG, RT and KT groups at any time point. Although heel eversion significantly increased over time due to fatigue, the taping conditions did not affect running kinematics. Conclusions : These findings suggest that neither RT nor KT alters running biomechanics in well-trained runners over prolonged treadmill running. The study highlights that taping, commonly used to prevent ankle injuries, does not significantly modify lower limb kinematics in the absence of injury. Further research is needed to evaluate the effects of taping in novice or injured runners and under more demanding conditions, such as overground running.