2,015 research outputs found

    Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

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    <p>Abstract</p> <p>Background</p> <p>Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.</p> <p>Methods</p> <p>Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. K<sub>V </sub>currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.</p> <p>Results</p> <p>Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, K<sub>V</sub>1.5 and 5-HT<sub>2A </sub>receptor mRNA and protein expression and K<sub>V </sub>current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.</p> <p>Conclusions</p> <p>In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.</p

    A model for evaluation of generic competences in engineering: application to the problem. Solving competence at the technical University of Madrid.

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    The competence evaluation promoted by the European High Education Area entails a very important methodological change that requires guiding support to help teachers carry out this new and complex task. In this regard, the Technical University of Madrid (UPM, by its Spanish acronym) has financed a series of coordinated projects with a two-fold objective: a) To develop a model for teaching and evaluating core competences that is useful and easily applicable to its different degrees, and b) to provide support to teachers by creating an area within the Website for Educational Innovation where they can search for information on the model corresponding to each core competence approved by UPM. Information available on each competence includes its definition, the formulation of indicators providing evidence on the level of acquisition, the recommended teaching and evaluation methodology, examples of evaluation rules for the different levels of competence acquisition, and descriptions of best practices. These best practices correspond to pilot tests applied to several of the academic subjects conducted at UPM in order to validate the model. This work describes the general procedure that was used and presents the model developed specifically for the problem-solving competence. Some of the pilot experiences are also summarised and their results analyse

    Development of a method of assessment of the problem-solving competence at the technical University of Madrid.

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    The competence evaluation promoted by the European High Education Area entails a very important methodological change that requires guiding support to help lecturers carry out this new and complex task. In this regard, the Technical University of Madrid (UPM, by its Spanish acronym) has financed a series of coordinated projects with the objective of developing a model for teaching and evaluating core competences and providing support to lecturers. This paper deals with the problem-solving competence. The first step has been to elaborate a guide for teachers to provide a homogeneous way to asses this competence. This guide considers several levels of acquisition of the competence and provides the rubrics to be applied for each one. The guide has been subsequently validated with several pilot experiences. In this paper we will explain the problem-solving assessment guide for teachers and will show the pilot experiences that has been carried out. We will finally justify the validity of the method to assess the problem-solving competence

    Development of a method of assessment of the problem-solving competency at the Technical University of Madrid

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    The competence evaluation promoted by the European High Education Area entails a very important methodological change that requires guiding support to help lecturers carry out this new and complex task. In this regard, the Technical University of Madrid (UPM, by its Spanish acronym) has financed a series of coordinated projects with the objective of developing a model for teaching and evaluating core competences and providing support to lecturers. This paper deals with the problem solving competence. The first step has been to elaborate a guide for teachers to provide an homogeneous way to asses this competence. This guide considers several levels of acquisition of the competence and provided the rubrics to be applied for each one. The guide has been subsequently validated with several pilot experiences. In this paper we will explain the problem-solving assessment guide for teachers and will show the pilot experiences that has been carried out. We will finally justify the validity of the method to assess the problem solving competence

    A model for evaluation of generic competences in engineering: application to the problem-solving competence at UPM.

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    The competence evaluation promoted by the European High Education Area entails a very important methodological change that requires guiding support to help teachers carry out this new and complex task. In this regard, the Technical University of Madrid (UPM, by its Spanish acronym) has financed a series of coordinated projects with a two-fold objective: a) To develop a model for teaching and evaluating core competences that is useful and easily applicable to its different degrees, and b) to provide support to teachers by creating an area within the Website for Educational Innovation where they can search for information on the model corresponding to each core competence approved by UPM. Information available on each competence includes its definition, the formulation of indicators providing evidence on the level of acquisition, the recommended teaching and evaluation methodology, examples of evaluation rules for the different levels of competence acquisition, and descriptions of best practices. These best practices correspond to pilot tests applied to several of the academic subjects conducted at UPM in order to validate the model. This work describes the general procedure that was used and presents the model developed specifically for the problem-solving competence. Some of the pilot experiences are also summarised and their results analyse

    Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study

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    Background: Epidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied. Methods: In this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004-20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance. Findings: Serotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004-20. Interpretation: The increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.This work was supported by the Spanish Ministry of Science and Innovation (grant PID2020–119298RB-I00), Meiji Pharma Spain (grant MVP 119/20), and internal funding from Instituto de Salud Carlos III.S

    Supuestos teóricos acerca del proceso auditivo en la enseñanza-aprendizaje de lenguas extranjeras

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    This article addresses a problem related to the auditory process in the teaching-learning of foreign languages, aimed at the importance of the development of skills in the English language. The objective of the research: To develop skills in the auditory process in the teaching-learning of foreign languages. Through techniques and methods where students can develop listening skills in a foreign language teaching-learning process. Pedagogical theories were also addressed, such as: Behavioral Theory, Humanist Theory, Theory of cognitivism, socio-cultural or socio-historical theory and theory of constructivism. It provides a correct methodology that will make it possible to raise the quality of the Foreign Language student, where it values the importance of developing foreign language skills. The practical theoretical experience will make it possible to verify that the coordinated application of active participation strategies will favor the leading role of students in meaningful and functional learning experiences for the development of their listening skills in the foreign language; it is a quantitative experimental design of the face-to-face modality.El presente artículo aborda una problemática relacionada con el proceso auditivo en la enseñanza-aprendizaje de lenguas extranjeras, dirigida a la importancia del desarrollo de habilidades en el idioma inglés. El objetivo de la investigación: Desarrollar habilidades en el proceso auditivo en la enseñanza-aprendizaje de lenguas extranjeras. A través de técnicas y métodos donde los estudiantes puedan desarrollar la habilidad de listening en un proceso de enseñanza-aprendizaje de lenguas extranjeras. Se abordaron además teorías pedagógicas como: Teoría Conductista, Teoría humanista, Teoría del cognitivismo, teoría socio cultural o socio histórico y teoría del constructivismo. En él se aporta una correcta metodología que posibilitará la elevación de la calidad del estudiante de Lenguas Extranjeras, donde valore la importancia de desarrollar habilidades de la lengua extranjera. La experiencia teórica práctica posibilitará comprobar que la aplicación coordinada de estrategias de participación activa favorecerá el papel protagónico de los estudiantes en experiencias de aprendizaje significativo y funcional para el desarrollo de sus habilidades auditivas en el idioma extranjero, es un diseño cuantitativo experimental de la modalidad presencial.&nbsp; Las técnicas usadas en la investigación fueron encuestas, entrevistas observaciones

    IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations

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    Using non-small cell lung carcinoma (NSCLC) cells harboring the erlotinib-sensitizing Epidermal Growth Factor Receptor (EGFR) exon 19 mutation delE746-A750, we developed erlotinib-refractory derivatives in which hyperactive Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling associated with enrichment in epithelial-to-mesenchymal transition (EMT)-related morphological and transcriptional features. We then explored whether an IGF-1R/EMT crosstalk was sufficient to promote erlotinib refractoriness in the absence of second-site EGFR mutations, MET and AXL hyperactivation. Transforming Growth Factor-beta1 (TGF beta 1)-induced mesenchymal trans-differentiation was sufficient to impede erlotinib functioning in the presence of drug-sensitive delE746-A750 EGFR mutation. Pharmacological blockade of IGF-1R fully prevented the TGF beta 1's ability to activate an EMT protein signature [E-cadherin low/vimentin high]. The sole presence of erlotinib was capable of rapidly activate an IGF-1R-dependent, vimentin-enriched mesenchymal-like phenotype in delE746-A750-mutated epithelial cells. Even if transient, NSCLC cells' intrinsic plasticity to undergo crosstalk between IGF-1R and EMT signaling pathways can sufficiently eliminate the erlotinib-sensitizing effect of highly prevalent EGFR mutations and suggests the urgent need for dual IGF-1R/EMT-targeting strategies to circumvent erlotinib resistance

    Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo

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    The flavolignan silibinin was studied for its ability to restore drug sensitivity to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)-driven resistance to erlotinib. As a single agent, silibinin significantly decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by approximately 50%. Furthermore, the complete abrogation of tumor growth was observed with the co-treatment of erlotinib and silibinin. Silibinin fully reversed the EMT-related high miR-21/low miR-200c microRNA signature and repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in erlotinib-refractory tumors. Silibinin was sufficient to fully activate a reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC cells. Given that the various mechanisms of resistance to erlotinib result from EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk thistle extract might be a suitable candidate therapy for upcoming clinical trials aimed at preventing or reversing NSCLC progression following erlotinib treatment
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