Estudi de l'efecte de la curcumina en la reversió de la resistència adquirida a oxaliplatí mitjançant la inhibició de la via de senyalització de NF-kB en models cel·lulars de càncer colorectal /

La resistència a oxaliplatí és un procés multifactorial i complex que afecta al desenllaç clínic dels pacients amb càncer colorectal (CRC) metastàtic tractats amb aquest fàrmac. La desregulació de la via de senyalització de NF-κB ha estat proposada com un important mecanisme implicat en aquest fenòmen. En aquest treball, hem observat que NF-κB es troba hiperactivat en models in vitro de resistència adquirida a oxaliplatí però la seva activació és atenuada mijançant l'addició de curcumina, un inhibidor no tòxic de NF-κB. El tractament concomitant d'oxaliplatí + curcumina va resultar ser més efectiu i sinèrgic en les línies cel·lulars amb resistència adquirida a oxalipatí promovent la reversió del seu fenotip resistent mitjançant la inhibició de la cascada de senyalització de NF-κB. L'anàlisi transcriptòmic va revelar la sobreexpressió de tres quimiocines regulades per NF-κB a nivell transcripcional, CXCL8, CXCL1 i CXCL2, en la línia resistent a oxaliplatí. Alhora, l'expressió d'aquestes quimiocines disminuia de manera més eficient en la línia resistent després del tractament combinat d'oxaliplatí + curcumina en comparació amb les cèl·lules sensibles a oxaliplatí. A més a més, el silenciament gènic de CXCL8 i CXCL1 es va traduir en un augment de la sensibilitat a oxaliplatí en les cèl·lules resistents mitjançant la inhibició de la via de senyalització Akt/NF-κB. Una alta expressió de CXCL1 en mostres fixades amb formol i incloses en parafina d'explants de metàstasis hepàtiques derivades de pacients amb CCR avançat es va associar amb la resposta al tractament combinat d'oxaliplatí + curcumina. En conclusió, els nostres resultats suggereixen que la combinació d'oxaliplatí + curcumina pot ser un tractament efectiu en pacients amb CCR i que l'expressió de CXCL1 podria utilitzar-se com a marcador predictiu de bona resposta a aquest tractament.Resistance to oxaliplatin is a complex process affecting the outcome of metastatic colorectal cancer (CRC) patients treated with this drug. De-regulation of the NF-κB signalling pathway has been proposed as an important mechanism involved in this phenomenon. In this work, we show that NF-κB was hyperactivated in in vitro models of oxaliplatin-acquired resistance but was attenuated by the addition of curcumin, a non-toxic NF-κB inhibitor. The concomitant combination of curcumin + oxaliplatin was more effective and synergistic in cell lines with acquired resistance to oxaliplatin, leading to the reversion of their resistant phenotype, through the inhibition of the NF-κB signalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-κB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells that were more efficiently down-regulated after oxaliplatin + curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to oxaliplatin through the inhibition of the Akt/NF-κB pathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastases was associated with response to oxaliplatin + curcumin. In conclusion, we suggest that combination of oxaliplatin + curcumin could be an effective treatment, for which CXCL1 could be used as a predictive marker, in CRC patients

Developing speaking competences in technical English for Spanish civil engineering students

[EN] Traditionally, Spanish schools of civil engineering provide their students a class on “Technical English” in order to develop their language skills. However, this class does not cover all the skills that the student would need in the labor market and mainly focuses in the reading and writing skills, and in a lower degree in the speaking and listening ones. This paper proposes a series of innovative and informal training activities (cine-forum on technical civil engineering topics and role playing on real professional situations) that allow Spanish civil engineering students to develop English skills that can rarely be worked in the classroom (i.e. speaking, negotiating and conversing), encouraging debate, participation, and fostering their self-confidence to speak about technical-English topics in public. Although the students’ level of English is much lower than expected, they all agree on the importance of technical English for their future career. The results also show the students’ lack in skills that are difficult to train in regular classes (speaking and talking). Consequently, this situation would require to provide complementary activities like the ones suggested in this project in order to develop these skills and increase the students’ demand for engineering classes taught in English.Romero De Ávila Serrano, V.; Diaz García, S.; Asensio Sánchez, L.; Lozano Galant, JA.; Moyano Enríquez De Salamanca, A.; Porras Soriano, R.; Poveda Bautista, E.... (2017). Developing speaking competences in technical English for Spanish civil engineering students. En Proceedings of the 3rd International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 1228-1236. https://doi.org/10.4995/HEAD17.2017.55641228123

Developing Students’ Communication in Technical English with Project Based Learning Methodology

Technical communication is an extremely important soft skill for civil engineers at the workplace. Due to globalization trends this technical communication often should be performed in English. If we join the fact that undergraduate engineering programs in Spain have been taught exclusively in Spanish, with which in addition, in rare cases those programs provide intentionally placed discipline-specific technical communication experiences, this all amounts to a major problem, regarded as an obstacle that limit undergraduates’ opportunities to work abroad. Aware of this problem, some schools provide their students with a brief course on “Technical English”. However, this course does not cover all the skills that the student would need in the labour market, such as speaking and listening abilities. This paper promotes an innovative teaching methodology that allows Spanish Civil Engineering students to hone English communication skills through “Lunch&Movies” sessions. In each session a documentary about technical Civil Engineering topics is shown. After the screening, students work in small inter-cohort groups with a guiding lecturer. These groups debate on different questions related to the video, encouraging participation, and fostering their self-confidence to talk about technical English topics in public. Different surveys were developed to demonstrate the students’ interest in learning technical English, and to evaluate the benefit for the attendees and their achievements. The results show that the students are conscious of the importance of technical English for their future careers, and most of them improved their initial level as the sessions progressed and they gained confidence in the foreign language. Also, through a pilot subject in English, it was demonstrated that the participants of the “Lunch&Movies” sessions obtained better oral qualifications than those who did not participate. In fact, the overall results indicated that Lunch & Movie sessions can improve students' technical oral skills as well as their own perceptions of their abilities

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

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

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Al-Bustān. Las fincas aristocráticas y la construcción de los paisajes periurbanos de al-Ándalus y Sicilia

Navarro Palazón, Julio, editorLa presente publicación se enmarca en el Proyecto I+D+i «Almunias medievales en el Mediterráneo: Historia y conservación de los paisajes culturales periurbanos» (PID2019-111508GB-I00, dirigido por Julio Navarro Palazón), del Ministerio de Ciencia e Innovación. Agencia Estatal de Investigación. Proyectos de I+D+i, de los Programas Estatales de Generación de Conocimiento y fortalecimiento Científico y Tecnológico del Sistema de I+D+i y de I+D+i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020. Esta obra es también un fruto destacado del trabajo realizado en el marco de la Unidad Asociada de I+D+i Patrimonio Cultural Árabe e Islámico, Consejo Superior de Investigaciones Científicas-Universidad de Granada, a través de la Escuela de Estudios Árabes de Granad

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension