Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential

Background: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. Objective: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10−5 to 10−9 M. Results: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10−9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10−6 M or 10−7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. Conclusions: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.FEDER/Junta de Andalucía-Consejería de Universidad, Investigación e Innovación/B-CTS-134-UGR20 Projec

Comparison of the capacity of three nonparametric person-fit indices to detect different aberrant response patterns on real data

Amb el suport del Consell Superior d'Avaluació de CatalunyaIntroduction: A total test score obtained as the sum of correct answers to items may provide a false picture of the actual level of competence of the person evaluated if it is the result of an aberrant response pattern (ARP). To detect possible ARP's a long list of person-fit indices are available. We study the behavior of three group-based or nonparametric person-fit indices, namely the Harnisch and Linn' Modified Caution Index (MCI), Van der Flier' U3 and Sijtsma' HT. The aim of the study is to evaluate the sensitivity of the extreme values of these indices to detect different types of ARP. Method: The indices are calculated on responses to basic skills test administered to the entire population of students of sixth year of primary school (11-12 years) made by the Catalan Evaluation Council of the Education System. The work focuses on a sample of students who meet the criterion of having obtained in any of the three indices considered, one above the 95th percentile, the ARP presence indicator score. To classify different types of ARP, we propose a procedure based on the grouping of items by level of difficulty, and to identify the kind of items where the successes and errors are concentrated. Results: The results indicate that the most aberrant patterns are best detected by the U3. MCI and HT show similar behavior and better detect response patterns that deviate from those expected in items of moderate to high difficulty. The maximum percentage of coincidence of the three indices is observed in identifying patterns that focuses on fewer correct answers than expected among the easy items and more correct answers than expected among the most difficult items. Conclusion: In our study, conducted with real data and a new way of characterizing patterns, we have observed that the indices show different sensitivities for detecting different ARP. Our results complement those obtained in other studies based on simulated data. All these results should be taken into account when choosing the index that best suits the characteristics of the test being evaluated and the type of ARP to be detected

Exantema fijo medicamentoso por paracetamol. Caso clínico con revisión bibliográfica

El exantema fijo medicamentoso es una toxicodermia caracterizada por la aparición de una lesión cutánea en forma de mácula de color rojizo o violáceo, redonda u oval, edematosa, bien delimitada, y que presenta recurrencias tras la administración del agente causal, generalmente un fármaco. Puede ser producido por una gran variedad de fármacos, entre ellos el paracetamol. El paracetamol es un medicamento con propiedades analgésicas y antipiréticas ampliamente conocido y utilizado por su amplio margen de seguridad y elevada biodisponibilidad. Sin embargo, se han descrito reacciones cutáneas adversas de diferentes tipos e intensidad tras su administración, fundamentalmente urticaria y angioedema, y con menor frecuencia eritema multiforme, necrólisis epidérmica tóxica, exantema fijo y púrpura de Henoch-Schönlein. Se presenta el caso de un usuario tipo con exantema fijo medicamentoso relacionado con el consumo de paracetamol. Se ha realizado una revisión bibliográfica sobre los diversos hallazgos clínicos y el diagnóstico diferencial entre las diferentes toxicodermias, así como el manejo y abordaje de las lesiones basado en el concepto TIME

Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.This research was funded by the Basque Department of Health, grant numbers 2020111043, 2018111086 and 2019111085 to I.G.-S., J.R.B. and N.F.-J., respectively

A Systematic Two-Sample Mendelian Randomization Analysis Identifies Shared Genetic Origin of Endometriosis and Associated Phenotypes

Endometriosis, one of the most common gynecological disorders, is a complex disease characterized by the growth of endometrial-like tissue in extra-uterine locations and is a cause of pelvic pain and infertility. Evidence from observational studies indicate that endometriosis usually appears together with several other phenotypes. These include a list of autoimmune diseases, most of them more prevalent in women, anthropometric traits associated with leanness in the adulthood, as well as female reproductive traits, including altered hormone levels and those associated with a prolonged exposure to menstruation. However, the biological mechanisms underlying their co-morbidity remains unknown. To explore whether those phenotypes and endometriosis share a common genetic origin, we performed a systematic Two-Sample Mendelian Randomization (2SMR) analysis using public GWAS data. Our results suggest potential common genetic roots between endometriosis and female anthropometric and reproductive traits. Particularly, our data suggests that reduced weight and BMI might be mediating the genetic susceptibility to suffer endometriosis. Furthermore, data on female reproductive traits strongly suggest that genetic variants that predispose to a more frequent exposure to menstruation, through earlier age at menarche and shorter menstrual cycles, might also increase the risk to suffer from endometriosis

Contribución de los ítems a los patrones atípicos de respuesta : cálculo del índice de precaución modificado sin el ítem

Amb el suport del Consell Superior d'Avaluació de CatalunyaAl diseñar una prueba de conocimientos conviene tener en cuenta que sus elementos, los ítems, han de tener diferentes niveles de dificultad. Cada persona debería ser capaz de superar la dificultad de los ítems hasta un determinado umbral que debería determinar su nivel de conocimiento. En términos generales, se espera que las personas evaluadas contesten correctamente a las preguntas fáciles y fallen las difíciles. Cuando esta pauta de respuesta se rompe de forma repetida, las respuestas son atípicas y dan lugar a puntuaciones que no se corresponden con el verdadero nivel evaluado. Las respuestas atípicas pueden evaluarse con indicadores, como el índice de precaución modificado (IPM). Este índice se basa en la covariación del patrón de respuestas, codificados como 1 (respuesta correcta) y 0 (respuesta incorrecta) con el vector de dificultades de los ítems. Los ítems más difíciles acertados correctamente o los más fáciles respondidos incorrectamente, tienen un gran peso en la identificación de una pauta de respuesta como atípica. El conocimiento de los ítems que están implicados en una pauta atípica es de gran interés en las evaluaciones formativas, esto es, cuando se aprovecha la información que ofrece dicha pauta para proporcionar retroalimentación acerca del proceso de aprendizaje y proporcionar elementos de mejora del mismo. El índice IPM puede calcularse con la instrucción Cstar del paquete Perfit de R (Tendeiro, 2015). Para identificar los ítems implicados en patrones atípicos, hemos programado una rutina en R que permite calcular el IPM sin el ítem. Los valores del IPM que disminuyen cuando se elimina un determinado ítem del análisis, señalan a ese ítem como contribuyente de una pauta de respuesta atípica. Por el contrario, los valores que aumenten al eliminar un ítem apuntan a ítems que no contribuyen a una pauta de respuesta atípica. El trabajo se ilustra con un ejemplo el funcionamiento de la rutina

Octava evaluación de test editados en España : una experiencia participativa

La Comisión de Test del Consejo General de la Psicología en España promueve anualmente la revisión de la calidad de diferentes test publicados. Este trabajo tiene un doble objetivo: a) presentar los resultados de la octava edición y b) considerar la aportación de la universidad en dicho proceso. En esta edición participaron 10 especialistas, 332 estudiantes y siete profesores, adaptándose el protocolo estándar de revisión al formato aprendizaje-servicio. En cuanto a los resultados, la calidad de los 11 test evaluados fue adecuada (promedio de 3,9 puntos en una escala 1-5) y similar a años anteriores (r = 0,90). El desarrollo y la baremación fueron puntos fuertes, mientras que se proponen mejoras en otros aspectos. El aprendizaje-servicio contribuyó a la diversificación de voces en el proceso observándose una calidad similar entre los informes del estudiantado y los emitidos por especialistas y un grado de acuerdo esperable (r = 0,67) entre ellos. Concluimos que el presente proyecto ha permitido identificar la oportunidad de profundizar en el uso de lenguaje compartido para fortalecer la comunicación entre las casas editoriales, la comisión promotora del modelo español de revisión de test, y las personas usuarias de los test, particularmente si se trata de principiantes.Every year, the Test Commission of the Spanish Psychological Association promotes the assessment of the test quality of several published tests. The aim of the present study is two-fold: a) to present results for the eighth review, and b) to consider the contribution of the universities in this process. Ten experts, 332 students, and seven professors participated in this edition and the standard protocol for review was aligned towards a service-learning format. For the 11 tests assessed, results showed an adequate quality (average of 3.9 points on a 1-5 rating scale) similar to previous years (r = .90). The strengths were test development and standardization, and a number of proposals for improving other sections were suggested. The service-learning approach contributed to the diversification of voices in the process with students' and experts' reports showing similar quality and an expected level of agreement (r = .67). We conclude that this project has helped to identify the opportunity to further deepen the use of shared language in order to strengthen the communication between the test publishers, the promoters of the Spanish model of testassessment, and the test users, especially in the case of beginners

Decreasing the Expression of GABAA[alfa]5 Subunit-Containing Receptors Partially Improves Cognitive, Electrophysiological, and Morphological Hippocampal Defects in the Ts65Dn Model of Down Syndrome

Trisomy 21 or Down syndrome (DS) is the most common cause of intellectual disability of a genetic origin. The Ts65Dn (TS) mouse, which is the most commonly used and best-characterized mouse model of DS, displays many of the cognitive, neuromorphological, and biochemical anomalies that are found in the human condition. One of the mechanisms that have been proposed to be responsible for the cognitive deficits in this mouse model is impaired GABAmediated inhibition. Because of the well-known modulatory role of GABAA ?5 subunit-containing receptors in cognitive processes, these receptors are considered to be potential targets for improving the intellectual disability in DS. The chronic administration of GABAA ?5-negative allosteric modulators has been shown to be procognitive without anxiogenic or proconvulsant side effects. In the present study, we use a genetic approach to evaluate the contribution of GABAA ?5 subunit-containing receptors to the cognitive, electrophysiological, and neuromorphological deficits in TS mice.We show that reducing the expression of GABAA ?5 receptors by deleting one or two copies of the Gabra5 gene in TS mice partially ameliorated the cognitive impairments, improved longterm potentiation, enhanced neural differentiation and maturation, and normalized the density of the GABAergic synapse markers. Reducing the gene dosage of Gabra5 in TS mice did not induce motor alterations and anxiety or affect the viability of the mice. Our results provide further evidence of the role of GABAA ?5 receptor-mediated inhibition in cognitive impairment in the TS mouse model of DS.This work was supported by the Jérôme Lejeune Foundation, Fundación Tatiana Pérez de Guzmán el Bueno and the Spanish Ministry of Economy and Competitiveness (PSI2016-76194-R/ AEI/FEDER/UE

Overexpression of Dyrk1A Is Implicated in Several Cognitive, Electrophysiological and Neuromorphological Alterations Found in a Mouse Model of Down Syndrome

Down syndrome (DS) phenotypes result from the overexpression of several dosage-sensitive genes. The DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A) gene, which has been implicated in the behavioral and neuronal alterations that are characteristic of DS, plays a role in neuronal progenitor proliferation, neuronal differentiation and long-term potentiation (LTP) mechanisms that contribute to the cognitive deficits found in DS. The purpose of this study was to evaluate the effect of Dyrk1A overexpression on the behavioral and cognitive alterations in the Ts65Dn (TS) mouse model, which is the most commonly utilized mouse model of DS, as well as on several neuromorphological and electrophysiological properties proposed to underlie these deficits. In this study, we analyzed the phenotypic differences in the progeny obtained from crosses of TS females and heterozygous Dyrk1A (+/-) male mice. Our results revealed that normalization of the Dyrk1A copy number in TS mice improved working and reference memory based on the Morris water maze and contextual conditioning based on the fear conditioning test and rescued hippocampal LTP. Concomitant with these functional improvements, normalization of the Dyrk1A expression level in TS mice restored the proliferation and differentiation of hippocampal cells in the adult dentate gyrus (DG) and the density of GABAergic and glutamatergic synapse markers in the molecular layer of the hippocampus. However, normalization of the Dyrk1A gene dosage did not affect other structural (e.g., the density of mature hippocampal granule cells, the DG volume and the subgranular zone area) or behavioral (i.e., hyperactivity/attention) alterations found in the TS mouse. These results suggest that Dyrk1A overexpression is involved in some of the cognitive, electrophysiological and neuromorphological alterations, but not in the structural alterations found in DS, and suggest that pharmacological strategies targeting this gene may improve the treatment of DS-associated learning disabilities

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio