GAP, an aequorin-based fluorescent indicator for imaging Ca2+ in organelles

Producción CientíficaGenetically encoded calcium indicators allow monitoring subcellular Ca2+ signals inside organelles. Most genetically encoded calcium indicators are fusions of endogenous calcium-binding proteins whose functionality in vivo may be perturbed by competition with cellular partners.We describe here a novel family of fluorescent Ca2+ sensors based on the fusion of two Aequorea victoria proteins, GFP and apo-aequorin (GAP). GAP exhibited a unique combination of features: dual-excitation ratiometric imaging, high dynamic range, good signal-to-noise ratio, insensitivity to pH and Mg2+, tunable Ca2+ affinity, uncomplicated calibration, and targetability to five distinct organelles. Moreover, transgenic mice for endoplasmic reticulum-targeted GAP exhibited a robust long-term expression that correlated well with its reproducible performance in various neural tissues. This biosensor fills a gap in the actual repertoire of Ca2+ indicators for organelles and becomes a valuable tool for in vivo Ca2+ imaging applications

Efficacy and Safety of a Novel Submucosal Injection Solution for Resection of Gastrointestinal Lesions

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are minimally invasive and efficient techniques for the removal of gastrointestinal (GI) mucosal polyps. In both techniques, submucosal injection solutions are necessary for complete effectiveness and safety during the intervention to be obtained. The main objective of this study was to evaluate the efficacy and safety of a new sterile submucosal injection solution for EMR/ESD used within a clinical protocol in patients with intestinal polyps. We carried out a prospective study between 2016 and 2017 with patients who attended the Endoscopy Consultation—Digestive Department of Primary Hospital. Patients were selected for EMR/ESD after the application of clinical protocols. Thirty-six patients were selected (≥ 66 years with comorbidities and risk factors). Lesions were located mainly in the colon. Our solution presented an intestinal lift ≥ 60 min in EMR/ESD and a high expansion of tissue, optimum viscosity, and subsequent complete resorption. The genes S100A9 and TP53 presented an expression increase in the distal regions. TP53 and PCNA were the only genes whose expression was increased in polyp specimens vs. the surrounding tissue at the mRNA level. In EMR/ESD, our solution presented a prolonged effect at the intestinal level during all times of the intervention. Thus, our solution seems be an effective and safe alternative in cases of flat lesions in both techniques.Study co-financed by the Junta de Andalucia (PIN-0479-2016, CTS676, CTS235, CTS164), the Ministry of Economy and Competitivity, Spain (SAF2017-88457-R, AGL2017-85270-R), Nakafarma S.L and CIBERehd is funded by Instituto de Salud Carlos III, Spain. The sponsors had no role in the design, execution, interpretation, or writing of the study

Estrategias en la formación matemático-didáctica de los estudiantes del Grado en Educación Infantil

© 2023 SCPM . This manuscript version is made available under the CC-BY-NC 4.0 license http://creativecommons.org/licenses/by-nc/4.0/ This document is the Published version of a Published Work that appeared in final form in NÚMEROS: Revista de Didáctica de las Matemáticas.Este trabajo presenta una propuesta para la formación en matemáticas de los futuros maestros de Educación Infantil. Se muestra la práctica llevada a cabo con estudiantes del Grado en Educación Infantil de una universidad pública estatal con el objetivo principal de conseguir que el alumnado individualizara gráficamente las propiedades del material lógico y lo hiciera de forma constructivista. Los participantes experimentaron una situación didáctica de aprendizaje por adaptación al medio (en el sentido de Brousseau), con momentos de acción, de formulación de diversos tipos, de validación por la propia situación y de institucionalización del conocimiento construido. Los resultados muestran que los participantes lograron adquirir las competencias lógico-matemáticas remarcando la eficacia e idoneidad de este tipo de actividades para conseguir nuevos conocimientos y habilidades. ------------------------------------------------------------------------------This paper presents a proposal for the mathematics training of future Early Childhood Education teachers. It shows the practice carried out with students of the Degree in Early Childhood Education at a state public university with the main objective of getting students to graphically individualise the properties of logical material and to do so in a constructivist way. The participants experienced a didactic situation of learning by adaptation to the environment (in Brousseau's sense), with moments of action, of formulation of various kinds, of validation by the situation itself and of institutionalisation of the knowledge constructed. The results show that the participants succeeded in acquiring logical-mathematical competences, highlighting the effectiveness and suitability of this type of activity for acquiring new knowledge and skill

Estudos Luso-Hispanos de História do Direito II = Estudios Luso-Hispanos de Historia del Derecho II

This book brings together a set of studies that were presented and discussed at the III Spanish-Portuguese Meeting of Law Historians. They deal with central themes of the History of Law and Institutions in Modern and Contemporary eras, with special emphasis on the peninsular territories and also on the territories that made up, at different times, the Spanish and Portuguese empires. As a whole, they contribute to broaden and deepen the historical knowledge of aspects related to justice and the administration of the territories, the functioning of institutions (courts, universities, courts) and the discussion of legal concepts central to the knowledge of the legal-political doctrine produced at different times of a vast chronological period.Este libro reúne un conjunto de estudios que fueron presentados y discutidos en el III Encuentro hispano-luso de historiadores del Derecho. Tratan temas centrales de la historia del derecho y de las instituciones en la época moderna y contemporánea, con especial énfasis en los territorios peninsulares y también en los territorios que compusieron, en distintas épocas, los imperios español y portugués. En su conjunto, contribuyen a ampliar y profundizar el conocimiento histórico de aspectos relacionados con la justicia y la administración de los territorios, el funcionamiento de las instituciones (tribunales, universidades, Cortes) y la discusión de conceptos jurídicos centrales para el conocimiento de la doctrina jurídico-política producida en distintos momentos de un vasto período cronológico. = Neste livro reúne-se um conjunto de estudos que foram apresentados e discutidos no III Encontro hispano-luso de historiadores do Direito. Neles são abordados temas centrais da história do direito e das instituições na época moderna e contemporânea, com especial incidência nos territórios peninsulares e também nos territórios que integraram, em momentos diversos, os impérios espanhol e português. No seu conjunto, contribuem para o alargamento e o aprofundamento do conhecimento histórico de aspectos ligados à justiça e à administração dos territórios, ao funcionamento das instituições (tribunais, universidades, Cortes) e à discussão de conceitos jurídicos centrais para o conhecimento da doutrina jurídico-política produzida em momentos diferentes de um vasto período cronológico

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Intestinal tuberculosis and Crohn's disease: the importance and difficulty of a differential diagnosis.

Tuberculosis (TB) is the most prevalent infection worldwide and affects one third of the population, predominantly in developing countries. Intestinal TB (ITB) is the sixth most frequent extra-pulmonary TB infection. Crohn's disease (CD) is a chronic inflammatory bowel disease that arises from the interaction of immunological, environmental and genetic factors. Due to changes in the epidemiology of both diseases, distinguishing CD from ITB is a challenge, particularly in immunocompromised patients and those from areas where TB is endemic. Furthermore, both TB and CD have a predilection for the ileocecal area. In addition, they share very similar clinical, radiological and endoscopic findings. An incorrect diagnosis and treatment may increase morbidity and mortality. Thus, a great degree of caution is required as well as a familiarity with certain characteristics of the diseases, which will aid the differentiation between the two diseases

Incisional endoscopic therapy as a therapeutic alternative in esophageal anastomotic strictures refractory to conventional treatment.

Esophageal anastomotic strictures are a non-negligible cause of benign strictures and secondary dysphagia. It should be noted that these are often complex strictures, with a large ischemic-fibrotic component. Thus, they are difficult to treat due to their recurrence, despite endoscopic dilation. Endoscopic incisional therapy appears as a therapeutic alternative in this type of patient, which allows the elimination of the stenotic ring, with a good efficacy and safety profile. We present the case of a patient with postoperative esophageal strictures refractory to treatment with dilation and endoscopic prosthesis, who was finally satisfactorily treated with incisional therapy

Effects of experimental subclinical fasciolosis on the feeding behaviour of sheep

11 páginas.Ten female Churra breed sheep were experimentally infected with 25 Fasciola hepatica metacercariae daily during six days. The animals were offered pelleted lucerne and water ad libitum. Feed and water intake was automatically recorded by computer monitoring of electronic balances. Liver damage caused by flukes was ascertained by measuring the activities of aspartate amino transferase, glutamate dehydrogenase and gamma-glutamyl transferase. Serum bile acids and glucose concentrations were also measured. Maximum plasma enzyme values were found at 10 weeks post infection. Plasma bile acid concentration increased from six to 13 weeks post infection. Glycaemia was decreased from the fourth week post infection until the end of the experiment. Total daily food intake decreased maximally between six and 12 weeks post infection. The number of meals per day and time spent eating and drinking decreased along the experimental infection. The rate of eating and drinking increased progressively. An association between anorexia and liver damage is suggested.Peer Reviewe