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Background: Oxidative stress is a major signature of spinal cord injury (SCI). The altered levels of various oxidative stress markers have been demonstrated in acute and chronic SCI. However, the variation of these markers in patients with chronic SCI depending on the time since the initial injury has not been explored yet. Objective: Our aim was to measure plasma levels of malondialdehyde (MDA), a marker of lipid peroxidation in patients with SCI stratified in different periods of suffering the injury (0–5 years, 5–10 years, and more than 10 years). Patients and methods: This cross-sectional study enrolled patients with SCI (N = 105) from different periods of the lesion and healthy control (HC) subjects (N = 38): short period (SCI SP, N = 31, time of evolution less than 5 years); early chronic (SCI ECP, N = 32, time of evolution 5–15 years); and late chronic (SCI LCP, N = 42, time of evolution more than 15 years). The plasma levels of MDA were measured using a commercially available colorimetric assay. Results: Patients with SCI had significantly higher plasma levels of MDA than HC subjects. Receiver operating characteristic (ROC) curve analysis for plasma MDA levels in patients with SCI demonstrated areas under the curve (AUC) of 1 (HC vs. SCI-SP); 0.998 (HC vs. SCI-ECP); and 0.964 (HC vs. SCI-LCP). Additionally, three ROC curves were used to compare the different concentrations of MDA between the subgroups of patients with SCI, and the resulting AUCs were: 0.896 (SCI-SP vs. SCI-ECP); 0.840 (SCI-ECP vs. SCI-LCP); and 0.979 (SCI-SP vs. SCI-LCP). Conclusion: Plasma concentration of MDA can be considered as an oxidative stress biomarker to assess the prognosis of SCI in chronic stages.

El estudiodel impacto de las innovaciones educativas sobre el aprendizaje producido en las asignaturas universitarias, requiere medir los efectos del cambio metodológico sobre diversas variables asociadas a la mejora del aprendizaje. En esta revisión mostramos e ilustramos cómo realizar una serie de medidas sobre algunas de estas variables: la implicación de los alumnos en la asignatura, el tiempo de estudio de los alumnos, el rendimiento académico (cuantificando las tasas de éxito y de fracaso), el aprendizaje (calificaciones medias obtenidas en las pruebas de evaluación del aprendizaje). El impacto sobre estas variables puede cuantificarse por el tamaño de efecto (g) que relaciona el nivel de cambio observado en la variable de estudio con respecto a su nivel de variación inicial estimado por su desviación estándar. Finalmente, desde la perspectiva del alumno es importante conocer cuál es su percepción y valoración sobre el cambio metodológico experimentado. En esta revisión aportamos ejemplos de casos que ilustran cómo pueden estudiarse los efectos del modelo de aula invertida sobre la implicación, el aprendizaje y la valoración de los alumnos sobre el cambio de metodología de enseñanza y el aprendizaje y mostramos los resultados que hemos obtenido. Utilizando estas metodologías demostramos que la puesta en práctica del aula inversa en asignaturas universitarias estimula el trabajo de los alumnos, aunque usualmente se requieren 2-3 años de práctica para vencer la resistencia estudiantil inicial y lograr su máximo impacto sobre el rendimiento académico, el aprendizaje y la apreciación de su valor por los alumnos.aula inversa, implicación estudiantil, rendimiento académico, tamaño de efecto, aprendizaje activo, implicación estudiantil, motivación, gamificación., The study of the impact of educational innovations on student learning in university courses requires measurements of the effects of the methodological changes on several variables associated to the enhancement of learning. In this review we show how to perform measurements of the involvement of the students in the subject, the student study time, academic performance (quantifying passing and failure rates), and the learning (changes in average grades on learning assessment exams). The impact on these variables is quantified by the effect size (g) that relates the level of change observed in the study variable with respect to its level of initial variation estimated by its standard deviation. Finally, from a student's perspective it is important to know what the students' perception and assessment are about the methodological change experienced. In this work, we provide some examples of how can be studied the effect of the implementation of the inverted classroom model on the involvement, learning and assessment of students on the change in teaching methodology and learning, and we show the results we have obtained. Using these methodologies we demonstrate that the implementation of the flipped classroom in university courses stimulates the work of the students, although usually it takes 2-3 years of practice to overcome student resistance, to achieve its maximum impact on academic performance, student learning, and the student’s appreciation of its value.

CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-na&iuml, ve RA patients, we investigated the pattern of IFN&gamma, IL-4 and IL-17A expression by na&iuml, ve (TN), central (TCM), effector memory (TEM) and effector (TE) CD4+ subsets, their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFN&gamma, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4+T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-na&iuml, ve RA patients showed a significant expansion of IL-17A+, IFN&gamma, + and IL-17A+IFN&gamma, + CD4+T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing TN and TMC CD4+T-lymphocytes and IFN&gamma, producing TN, TCM, TEM CD4+T-lymphocytes with respect to responders. After 6 months, the numbers of CD4+IL-17A+TN remained significantly increased in nonresponders. In conclusion, CD4+T-lymphocytes in new-onset DMARD-na&iuml, ve RA patients show IL-17A and IFN&gamma, abnormalities in TN, indicating their relevant role in early disease pathogenesis. Different patterns of CD4+ modulation are identified in MTX responders and nonresponders.

Background: T lymphocytes are involved in the pathogenesis of nonallergic asthma. The objective of this study was to characterize the subset distribution and pattern of chemokine receptor expression in circulating T lymphocyte subsets from nonallergic asthma patients. Methods: Forty stable nonallergic asthma patients and 16 sex- and age-matched healthy donors were studied. Twelve patients did not receive inhaled steroids (untreated patients), 16 received 50-500 μg b.i.d. of inhaled fluticasone propionate (FP) (standard-dose patients), and 12 received over 500 μg b.i.d. of inhaled FP (high-dose patients) for at least 12 months prior to the beginning of this study and were clinically well controlled. Flow cytometry was performed using a panel of monoclonal antibodies (4 colors). Results: Nonallergic asthma patients treated with high doses of inhaled FP showed a significant reduction in the percentages of CD3+ T lymphocytes compared to healthy controls. Untreated patients showed a significant increase in CCR6 expression in CD8+CD25+ and CD8+CD25+bright T cells compared to healthy controls. The results were similar for CXCR3 and CCR5 expression. In patients treated with standard doses of FP, CCR5 expression was significantly increased in CD3+ T lymphocytes relative to healthy controls. Conclusions: The different groups of clinically stable nonallergic asthmatic patients showed distinct patterns of alterations in subset distribution as well as CCR6, CXCR3, and CCR5 expression on circulating T lymphocytes.

espanolEl aula invertida es un modelo de ensenanza-aprendizaje en el que los alumnos tienen el primer contacto con la informacion a ser aprendida fuera de clase, mediante documentos (textos y videos) que el docente les hace llegar por medios electronicos. El tiempo de clase asi ahorrado se dedica a actividades de aula que consolidan la asimilacion de ese conocimiento y lo aplican a la resolucion de cuestiones, casos y problemas. Este modelo de aprendizaje reduce el tiempo de instruccion directa en clase y aumenta el dedicado al aprendizaje activo. Se transfi ere al alumno la responsabilidad de esforzarse inicialmente para alcanzar un nivel de comprension basico y comunicar sus difi cultades y dudas al docente. Asi, el docente recibe informacion sobre cuales son las difi cultades y necesidades de sus alumnos y podra adaptar las activida-des que realizara en el aula para resolver las dudas manifestadas por ellos. Denominamos a esta metodologia ‘aula inver-tida adaptativa’. El aula invertida logra un mayor grado de implicacion de los alumnos con su aprendizaje, mejoras en la valoracion de su percepcion sobre la docencia recibida y, sobre todo, mejoras en sus resultados academicos. En este ar-ticulo tambien se sopesan los benefi cios y los costes del cambio desde la metodologia expositiva tradicional al aula inver-tida adaptativa y, fi nalmente, se aportan recomendaciones para la puesta en practica del aula invertida en el contexto de una ensenanza tradicional de las ciencias sanitarias. EnglishFlipped classroom means that students have the fi rst exposure to new information to be learned outside the classroom by mean of electronic documents (texts and videos). Next, class time is devoted to class activities which reinforce the assimilation of that knowledge by applying it to answer questions and solving cases and problems. This learning model reduces the class time devoted to direct instruction and increases the time used in active learning. It transfers to the student the responsibility of initially striving to reach a basic understanding and communicate their diffi culties and doubts to the teacher. Thus, the teacher receives information about the diffi culties and needs of their students and can adapt the activities they will carry out in the classroom to solve the doubts expressed by their students. We named this teaching methodology as adaptive fl ipped classroom. The fl ipped classroom achieves a greater degree of involvement of students with their learning, improvements in academic results and in their assessment of the teaching received. In this report, the benefi ts and costs of the change are weighed from the traditional expositive methodology to the adaptive fl ipped classroom and, fi nally, recommendations are given for the implementation of the fl ipped classroom in the context of a traditional teaching of health sciences.

ResumenProfesores de inmunología de la Universidad de Alcalá hemos implementado en los últimos cinco años el modelo de aula inversa en tres asignaturas del grado de Biología Sanitaria. El porcentaje de alumnos que estudiaron los materiales instructivos (documentos y vídeos) antes de que los temas fuesen tratados en clase ha aumentado desde valores minoritarios en los primeros años a porcentajes cercanos al 100% en los últimos años. La calificación media obtenida por los alumnos en las pruebas de evaluación del aprendizaje ha mejorado en las tres asignaturas en más de una desviación estándar con respecto a la que se obtenía con metodologías expositivas tradicionales antes de la implantación del modelo de aprendizaje inverso. Los porcentajes de alumnos que fracasan han disminuido y han aumentado los porcentajes de alumnos que alcanzan un nivel de maestría (calificación ¿8 en una escala de diez). Los alumnos reconocen desarrollar competencias con las actividades realizadas en los seminarios. El grado de satisfacción de los alumnos también ha aumentado. Concluimos que con el modelo inverso los alumnos universitarios dedican más trabajo no presencial al estudio de sus asignaturas y a consecuencia de ello sus calificaciones en la pruebas de evaluación del aprendizaje mejoran significativamente AbstractImmunology teachers form Alcala’s University implementes flipped classroom model in the last five years into three immunology courses in sanitary biology university degree. The percentage of students that studied the instructive materials (documents and videos) before class has increased from minority values in the first years to percentages close to 100% in the last years. The mean grade obtained by the classes in the learning assessment exams has increased in the three courses in more than one standard deviation with respect to the original mean obtained in each course with traditional expositive methods before the implementation of the flipped learning model. The percentages of failed students have decreased and those of students that attain mastery levels (grades ¿80% of the maximum grade) have increased. The students recognize that the flipped model helps them to develop competencies in the activities developed in the seminars. The degree of satisfaction with the teaching has also increased We can conclude that university students thanks to the flipped model devote more time of work to the study of flipped courses and as a consequence of this increase in study they learn more and obtain increased grades in the learning assessment exams.

The results obtained thanks to the flipped classroom with ‘just Iiin time’ teaching method are reviewed. This method allowed to know what the students did not understand after trying to study the instructive materials assigned to them. To achieve that the students work before class methods of marketing and gamification were developed. Methods for the analysis of student responses were also developed. The JiTT method allowes the teacher know in advance those aspects that are most interesting or most dificult to understand for the students as well as their most urgent doubts. Finally, we have developed methods to use the urgent doubts of the students to generate formative feedback and activities to do in the classroom. In the method named “flipped learning forte” the teacher answer the urgent doubts of his students. In the method named ‘flip in colours’ the teacher classify the doubts by their posible utility in the classroom using a color code. With the combined application of these methods in university courses the failure rate of the students has decreased and the mean grade in the exams for the assessment of learning has increased in more than one standard deviation. The rate of students that attain the level of mastery has increased, as well as the student evaluations about the teachers of these courses. Finally, the reasons underlying the efficacy of the proposed flipped method are discussed.