Heart regeneration after miocardial infarction using synthetic biomaterials

Myocardial infarction causes almost 7.3 million deaths each year worldwide. However, current treatments are more palliative than curative. Presently, cell and protein therapies are considered the most promising alternative treatments. Clinical trials performed until now have demonstrated that these therapies are limited by protein short half‐life and by low transplanted cell survival rate, prompting the development of novel cell and protein delivery systems able to overcome such limitations. In this review we discuss the advances made in the last 10 years in the emerging field of cardiac repair using biomaterial‐based delivery systems with focus on the progress made on preclinical in vivo studies. Then, we focus in cardiac tissue engineering approaches, and how the incorporation of both cells and proteins together into biomaterials has opened new horizons in the myocardial infarction treatment. Finally, the ongoing challenges and the perspectives for future work in cardiac tissue engineering will also be discussed

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.Acknowledgements: This work was supported by Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to MLM-C), Ministerio de Ciencia e Innovación CONSOLIDER-INGENIO 2010 Program Grant CSD2008-00005 (to LAMC); Spanish Ministry of Economy and Competitiveness Grant BFU2013-47531-R, BFU2016-77408-R, PID2019-109055RB-100 (to L.A.M.-C.) (MINECO/FEDER, UE); Asociación Española contra el Cáncer (MLM-C, TC-D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.), La Caixa Foundation Program (to M.L.M.-C.), Fundacion BBVA UMBRELLA project (to M.L.M.-C.), Ayuda RYC2020-029316-I financiada por MICIN/AEI/10.13039/501100011033 (to TC-D), Plataforma de Investigación Clínica-SCReN (PT17 0017 0020) (to M.I.-L.), programa retos RTC2019-007125-1 (to M.L.M.-C, J.S.), Proyectos Investigacion en Salud DTS20/00138 (to M.L.M.-C., J.S), ERA-Net E-Rare EJP RD Joint Translational Call for Rare Diseases FIGHT-CNNM2 (EJPRD19-040) and from Instituto Carlos III, Spain (REF G95229142) (to L.A.M.-C.), US National Institutes of Health under grant CA217817 (to D.B.), Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thankMINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644) and PhD fellowship fromMINECO (REF BES-2017-080435) awarded to I.G.-R. The collection and storage of patients tissues was supported by the Newcastle Biomedicine Biobank and the European Community’s Seventh Framework Programme (FP7/2001–2013) and Cancer Research UK awards Cancer Research UK grants C18342/A23390; C9380/A18084 and C9380/A26813. Finally, we would like to acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Bioinformatics analysis of mutations in SARSCoV- 2 and clinical phenotypes

1 p.-1 fig.-8 tab.Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially reported in Wuhan (China) hasspread worldwide. Like other viruses, SARS-CoV-2 accumulates mutations with each cycle of replication by continuously evolving a viral strain with one or more single nucleotide variants (SNVs). However, SNVs that cause severe COVID-19 or lead to immune escape or vaccine failure are not well understood. We aim to identify SNVs associated with severe clinical phenotypes.Methods: In this study, 27429 whole-genome aligned consensus sequences of SARS-CoV-2 were collected from genomic epidemiology of SARS-CoV-2 project in Spain (SeqCOVID) [1]. These samples were obtained from patients who required hospitalization and/or intensive care unit admission (ICU), excluding those registered in the first pandemic wave.Besides, 248 SARS-CoV-2 genomes were isolated from COVID-19 hospitalized patients from Gregorio Marañon General University Hospital (GMH) of which 142 were fully vaccinated. Bioinformatics tools using R and Python programming languages were developed and implemented comparing those to SARS-CoV-2 Wuhan-Hu-1 (reference genome).Results: Using a selection threshold mutational frequency 10%, 27 SNVs were expected to have association with hospitalization and ICU risk. The reference haplotype differing at the SNV coding for lysine at the residue 203 (N:R203K) was found to have negative association with COVID-19 hospitalization risk (p = 5.37 x 10-04). Similarly, a negative association was observed when the residue at 501 is replaced by tyrosine (S:N501Y) (p = 1.33 x 10-02). The application of a Chi-square test suggested that SNV-haplotypes coding for mutants residues such as (S:A222V, N:A220V, ORF10:V30L) and (ORF1a:T1001I, ORF1a:I2230T, S:N501Y, S:T716S, S:S982A, ORF8:Q27*, N:R203K, N:S235F) have negative associations with COVID-19 hospitalization risk (p = 6.58 x 10-07 and p = 2.27 x 10-16, respectively) and COVID-19 ICU risk (p = 1.15 x 10-02 and p = 2.51 x 10-02, respectively). Focusing on the SNV-haplotype coding the mutations (S:A222V, N:A220V, N:D377Y, ORF10:V30L) were observed to increase the risk of COVID-19 hospitalization (p = 2.71 x 10-04). Results from SARS-CoV-2 genomes analysis from GMH showed 63 coding SNVs which met the established threshold value. Applying a Chi-square test, the SNV-haplotype carrying coding variants for mutant residues in 5 ORF proteins and surface and membrane glycoprotein and nucleocapsid phosphoprotein was significantly associated with vaccine failure in hospitalized COVID-19 patients (p = 7.91 x 10-04).Conclusions: SNV-haplotypes carrying variants lead to non-synonymous mutations located along SARS-CoV-2 wholeproteome may influence COVID-19 severity and vaccine failure suggesting a functional role in the clinical outcome for COVID-19 patients.This research work was funded by the European Commission-NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global)Peer reviewe

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Evolutionary genomics of SARS-CoV-2: keys for viral success

Resumen del trabajo presentado al 44º Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Málaga del 6 al 9 de septiembre de 2022.Peer reviewe

Genomic surveillance and impact of SARS-CoV-2 mutations

Resumen del póster presentado a las II Jornadas Científicas PTI + Salud Global, celebradas los días 5 y 6 de octubre de 2022 en el Auditorio Santiago Grisolía de Valencia (España).Peer reviewe

¿Qué queda de mí?

Este libro es una reclamación a quienes hemos sido, somos o seremos docentes. A quienes no hemos respetado a las personas que se han puesto junto a nosotros y nosotras, confiando su bien más preciado: la libertad. Estas páginas denuncian cada vez que convertimos una visión en la visión, una emoción en la emoción, un saber en el saber, un comportamiento en el comportamiento. Es un grito contra la imposición, la normalización, la neutralización y la universalización de una perspectiva particular. Una pugna contra cada proceso que no se ha conectado con las vidas de los aprendices. Un texto colaborativo realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga y coordinado por Ignacio Calderón Almendros

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it