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Abstract Cell cycle checkpoints, activated by stressful events, halt the cell cycle progression, and prevent the transmission of damaged DNA. These checkpoints prompt cell repair but also trigger cell death if damage persists. Decision-making between these responses is multifactorial and context-dependent, with the tumor suppressor p53 playing a central role. In many tumor cells, p53 alterations lead to G1/S checkpoint loss and the weakening of the G2 checkpoint, rendering cell viability dependent on the strength of the latter through mechanisms not fully characterized. Cells with a strong pro-survival drive can evade cell death despite substantial DNA lesions. Deciphering the integration of survival pathways with p53-dependent and -independent mechanisms governing the G2/M transition is crucial for understanding G2 arrest functionality and predicting tumor cell response to chemotherapy. The serine/threonine kinase GRK2 emerges as a signaling node in cell cycle modulation. In cycling cells, but not in G2 checkpoint-arrested cells, GRK2 protein levels decline during G2/M transition through a process triggered by CDK2-dependent phosphorylation of GRK2 at the S670 residue and Mdm2 ubiquitination. We report now that this downmodulation in G2 prevents the unscheduled activation of the PI3K/AKT pathway, allowing cells to progress into mitosis. Conversely, higher GRK2 levels lead to tyrosine phosphorylation by the kinase c-Abl, promoting the direct association of GRK2 with the p85 regulatory subunit of PI3K and AKT activation in a GRK2 catalytic-independent manner. Hyperactivation of AKT is conditioned by p53’s scaffolding function, triggering FOXO3a phosphorylation, impaired Cyclin B1 accumulation, and CDK1 activation, causing a G2/M transition delay. Upon G2 checkpoint activation, GRK2 potentiates early arrest independently of p53 through AKT activation. However, its ability to overcome the G2 checkpoint in viable conditions depends on p53. Our results suggest that integrating the GRK2/PI3K/AKT axis with non-canonical functions of p53 might confer a survival advantage to tumor cells.

Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcome of patients with acute myeloid leukemia (AML). However, even before these innovations outcomes with intensive chemotherapy have improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5- year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate has dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients

Objective To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients.Methods Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3).Results Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p

Introducción: La Neuroartropatía de Charcot puede ser mal diagnosticada. Objetivo: Describir los elementos básicos para el diagnóstico de la Neuroartropatía de Charcot en personas con Diabetes mellitus. Material y Métodos: Se realizó una revisión bibliográfica descriptiva. Se utilizó como motor de búsqueda a Google Académico. Se empleo información de diferentes bases de datos. Las palabras clave utilizadas fueron: Diabetes mellitus; neuropatía diabética; neuroartropatía de Charcot; artropatía neuropática; pie de Charcot; pie diabético (en inglés y español). Se evaluaron artículos, que en general tenían menos de 10 años de publicados, en los idiomas referidos y que por el título trataban el tema de estudio. Fueron excluidos los que no abordaran la relación entre Diabetes mellitus y la neuroartropatía de Charcot. Se referenciaron 50 artículos. Desarrollo: La hiperglucemia persistente es causa de alteraciones neurotróficas, vasculares, inflamatorias e inmunológicas, que contribuyen a la aparición de la Neuroartropatía de Charcot, la cual se debe sospechar en personas con factores de riesgo que condicionan su aparición. Su diagnóstico es eminentemente clínico y puede evolucionar desde un estadio agudo (activo) a su etapa crónica (menos activa o inactiva). Las imágenes de Rx convencional y resonancia magnética de la zona afectada, pueden ayudar al diagnóstico positivo y diferencial. Conclusiones: El diagnóstico de la Neuroartropatía de Charcot, se realiza a través de la verificación de la existencia de factores de riesgo que condicionan su aparición en una persona con Diabetes mellitus. Su diagnóstico es predominantemente clínico y la imagenología, pueden ayudar al diagnóstico positivo y diferencial.

Resumen: La fístula aortoentérica es una entidad poco frecuente y con elevada mortalidad, que tratamos en los servicios de cirugía de forma ocasional. Clásicamente el tratamiento propuesto es la corrección mediante cirugía abierta con injerto protésico de Dacron y resección intestinal en el mismo acto. Dados los malos resultados, en los últimos años se han descrito algunos casos de tratamiento endovascular con implante de endoprótesis.Presentamos un caso de fístula aortoentérica resuelta mediante abordaje híbrido con implante de endoprótesis y posterior resección intestinal con sellado de la fístula a través de cirugía abierta. Se trataba de un paciente varón de 75 años que ingresó en nuestro hospital con síntomas de síndrome aórtico agudo y que evidenció en angiotomografía computarizada un aneurisma de aorta abdominal ya conocido de 8,4 × 8,4 × 9,5 cm y luz vascular de 5 × 3,4 cm, así como signos de infiltración de la grasa periaórtica que indicaban rotura de la luz vs. fístula aortoentérica. Dada la inestabilidad hemodinámica del paciente, se decidió implante urgente de endoprótesis con cirugía en un segundo tiempo en vez del abordaje abierto convencional. Se realizó el implante de endoprótesis sin incidencias iniciales, pero con necesidad de resellado por endofuga en el control de imagen posterior. En un segundo tiempo se realizó resección intestinal y cierre de la fístula, ya previamente sellada de forma directa. El paciente evolucionó favorablemente y fue dado de alta.El abordaje híbrido abierto y endovascular en enfermedades complejas y de alta mortalidad como es el caso de la fístula aortoentérica puede ofrecer una supervivencia mayor en pacientes con alta morbilidad. Abstract: Aorto-enteric fistula is a rare entity with high mortality, occasionally surgically treated. Classically, the proposed treatment is open surgical repair with a Dacron prosthetic graft and intestinal resection in the same act. Given the poor results, in recent years some cases of endovascular treatment with stent implantation have been described.We present a case of an aortoenteric fistula resolved by a hybrid approach through stent implantation and intestinal resection with fistulaa sealing by open surgery in a second stage. This is a 75-year-old male patient who was admitted to our hospital with symptoms of acute aortic syndrome. The CT aortogram revealed a known abdominal aortic aneurysm of 8.4 × 8.4 × 9.5 cm and a vascular luz of 5 × 3.4 cm with signs of periaortic fat infiltration suggesting luz rupture vs. aortoenteric fistula. Given the hemodynamic instability of the patient, the team decided on emergent EVAR implantation with intestinal resection surgery in a second stage. The endoprosthesis was implanted without initial incidents but a resealing had to be performed due to endoleak in the subsequent control CT aortogram. In a second stage, the team performed the intestinal resection and closure of the fistula. The patient recovered favorably and was discharged.The hybrid open and endovascular approach in complex pathologies with high mortality, such as aortoenteric fistula, may offer an alternative approach in patients with high morbidity.

RESUMEN El objetivo de este artículo es analizar los rasgos significativos de los estudiantes de la Sección Universitaria de Canarias (1913-1927) a través de los documentos propios de la institución académica. En el contexto de la época fue complicado el establecimiento de la enseñanza superior en las Islas Canarias (España). Las aspiraciones de las élites isleñas de contar con estudios universitarios, tras diversas gestiones con la intermediación de políticos, periodistas y profesores del instituto de bachillerato, se lograron en 1913, aunque dependientes de la Universidad de Sevilla. Empleamos la metodología de análisis histórico recurriendo a fuentes primarias y secundarias. Esta investigación contribuye a desvelar las singularidades de los estudiantes en la implantación de los estudios universitarios en Canarias, y a enriquecer la microhistoria, a la vez que se aporta una línea de investigación poco explotada y que puede extrapolarse a otros entornos geográficos.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Abstract Background Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments. Results We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again. Conclusions By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.

Abstract Objectives To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients. Methods Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group. Results RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p

El objetivo de esta revisión se centra en poner de manifiesto aquellas barreras y facilitadores que actualmente, según distintos estudios llevados a cabo, están marcando el proceso de inclusión educativa en el alumnado con TEA. Para ello, 24 artículos han sido analizados, atendiendo a las voces de los principales implicados en esta temática: las familias, los diferentes profesionales educativos y el propio alumnado. Los resultados encontrados se analizarán no solo según promuevan o dificulten el proceso hacia una educación inclusiva, sino también según la perspectiva de las distintas voces; mostrando, a su vez, los puntos de encuentro entre estos, así como las posibles discrepancias. Para finalizar, se expondrán una serie de conclusiones derivadas de los resultados, las cuales evidenciarán lo lejos que todavía nos encontramos de ver este derecho satisfecho. A su vez, a través de la identificación de ciertas barreras clave, también aflorarán una serie de pautas de actuación útiles con el fin de promover una reflexión que pudiera derivar en un acortamiento entre lo que se dice que debería hacerse y lo que finalmente se lleva a cabo.

Mathematic proficiency has long been associated with the male gender and with high levels of intelligence. Similarly, STEM careers have been linked to the male gender, so both ideas are central to the present article. This study aims to observe differences in attitudes towards mathematic and STEM careers, considering, on the one hand, gender differences and, on the other hand, intelligence, separating the latter variable into a high-ability group and a normative intelligence group. A mixed methods approach was used for the analysis due to its methodological richness, using a reduced version of the Expectations and Values Questionnaire (EVQ) analysed using SPSS v. 25 and two open-ended questions analysed qualitatively using the ALCESTE software. v.1. The results show differences as a function of intelligence, but no gender differences were observed. It is concluded that the results challenge historical conceptions of attitudes towards mathematic and STEM careers.

Abstract Background Patency of the false lumen in chronic aortic dissection (AD) is associated with aortic dilation and long-term aortic events. However, predictors of adverse outcomes in this population are limited. The aim of this study was to evaluate the relationship between aortic growth rate and false lumen flow dynamics and biomechanics in patients with chronic, patent AD. Methods Patients with a chronic AD with patent false lumen in the descending aorta and no genetic connective tissue disorder underwent an imaging follow-up including a contrast-enhanced 4D flow cardiovascular magnetic resonance (CMR) protocol and two consecutive computed tomography angiograms (CTA) acquired at least 1 year apart. A comprehensive analysis of anatomical features (including thrombus quantification), and false lumen flow dynamics and biomechanics (pulse wave velocity) was performed. Results Fifty-four consecutive patients with a chronic, patent false lumen in the descending aorta were included (35 surgically-treated type A AD with residual tear and 19 medically-treated type B AD). Median follow-up was 40 months. The in-plane rotational flow, pulse wave velocity and the percentage of thrombus in the false lumen were positively related to aortic growth rate (p = 0.006, 0.017, and 0.037, respectively), whereas wall shear stress showed a trend for a positive association (p = 0.060). These results were found irrespectively of the type of AD. Conclusions In patients with chronic AD and patent false lumen of the descending aorta, rotational flow, pulse wave velocity and wall shear stress are positively related to aortic growth rate, and should be implemented in the follow-up algorithm of these patients. Further prospective studies are needed to confirm if the assessment of these parameters helps to identify patients at higher risk of adverse clinical events.

La universidad desde sus inicios ha estado ligada al desarrollo histórico, social, político, económico y cultural de las naciones, por lo que la relación de la misma con la sociedad en que vivimos es de estrecha reciprocidad, e indisoluble. El triunfo de la Revolución el primero de enero de 1959, sería promotor de logros académicos y sociales en la Educación Superior, iniciaría un proceso de transformaciones continuas, dirigido a ampliar las posibilidades y oportunidades de acceso a la universidad a todas aquellas personas con posibilidades y deseos de hacerlo. Cuba se ha nutrido de cada uno de los eventos mundiales sobre educación médica, para que las nuevas innovaciones en la enseñanza universitaria, sean cambios en el paradigma existente. Nuestras universidades necesitan formar profesionales que defiendan su realidad, que sean actores protagónicos en la construcción del futuro. y que den solución a las necesidades del momento histórico que se vive. Palabras claves: Universidad, sociedad, transformaciones, educación.

Introducción: Los inhibidores de la ciclooxigenasa-2 suelen indicarse en pacientes con hipersensibilidad múltiple a los antiinflamatorios no esteroides. Sin embargo, se han descrito reacciones de hipersensibilidad inmediata y retardada, además de posible reactividad cruzada con sulfonamidas. Reporte del caso: Paciente masculino de 66 años, que acudió al servicio de Alergia por una reacción cutánea, luego de haber consumido un comprimido de celecoxib. Previamente, durante el tratamiento con etoricoxib, tuvo una reacción menor, sin establecer la correlación farmacológica. Se realizaron pruebas cutáneas (intraepidérmicas y epicutáneas), con resultados negativos, y un examen de exposición oral controlada con etoricoxib, con resultado positivo. Se comprobó la tolerancia a las sulfamidas. Conclusiones: El caso de reacción cutánea, mediante reactividad cruzada, entre etoricoxib y celecoxib expuesto en este artículo sugiere la necesidad de realizar pruebas de provocación para confirmar la tolerancia de cada fármaco antes de su prescripción. Por el contrario, trimetropim- sulfametoxazol pueden indicarse con seguridad, si fuese necesario.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification.

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

ObjectiveTo determine the optimal ultrasound (US) cut-off values for cranial and extracranial arteries intima media thickness (IMT) to discriminate between patients with and without giant cell arteritis (GCA).MethodsRetrospective observational study including patients referred to an US fast-track clinic. All patients underwent bilateral US examination of the cranial and extracranial arteries including the IMT measurement. Clinical confirmation of GCA after 6 months was considered the gold standard for diagnosis. A receiver operating characteristic (ROC) analysis was performed to select the cut-off values on the basis of the best tradeoff values between sensitivity and specificity.ResultsA total of 157 patients were included, 47 (29.9%) with clinical confirmation of GCA after 6 months. 41 (87.2%) of patients with GCA had positive US findings (61.7% had cranial and 44.7% extracranial involvement). The best threshold IMT values were 0.44 mm for the common temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery and 1 mm for the subclavian and axillary arteries. The areas under the ROC curves were greater for axillary arteries 0.996 (95% CI 0.991–1), for parietal branch 0.991 (95% CI 0.980–1), for subclavian 0.990 (95% CI 0.979–1), for frontal branch 0.989 (95% CI 0.976–1), for common temporal artery 0.984 (95% CI 0.959–1) and for common carotid arteries 0.977 (95% CI 0.961–0.993).ConclusionIMT cut-off values have been identified for each artery. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice.

BackgroundAtrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations.MethodsTwo hundred seventy-four subjects aged 65–75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately.ResultsAtrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665–0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654–0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively.ConclusionBlood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

ObjectivesTo determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS).MethodsA longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2).ResultsOf 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3–30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12–0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13–0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20–0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively.ConclusionsParadoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Background: Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. Methods: An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. Results: Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. Conclusions: Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generating.

Investigaciones actuales muestran que el engagement hacia el aprendizaje de la Matemática Discreta y su rendimiento académico no alcanzan los niveles deseados. Este trabajo pretende identificar las características de los estudiantes y las aulas que influyen en el engagement (EMD) hacia el aprendizaje de la Matemática Discreta y en el rendimiento académico (RMD). La muestra se compone de 728 estudiantes de primer curso agrupados en 40 aulas en la Universidad de Ciencias Informáticas (Cuba). Con el objetivo de conocer las variables de estudiantes y aulas que son predictoras de las variables dependientes se realizó un análisis multinivel multivariado. La autoeficacia percibida, la utilización de las tecnologías y la satisfacción con los materiales de estudio son factores de los estudiantes que explican el EMD y el RMD. A nivel de aula resultan significativas el tipo de actividad, el grado de retroalimentación que se logre y el ambiente de aprendizaje.

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LTP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.24-0.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE.

En las últimas décadas, las administraciones locales han adquirido progresivamente mayor protagonismo en la gestión urbana. En este contexto, las políticas urbanas (PP.UU.) como instrumentos para la mejora de las ciudades, resultan indispensables para la mejora de la calidad de vida de la ciudadanía. Esta razón, junto a derechos como proximidad o inclusión social, son compartidos por los Servicios Sociales (SS.SS.) y además guardan coherencia con los Objetivos de Desarrollo Sostenible. La finalidad de esta investigación se centra en relacionar precisamente los conceptos de política urbana (P.U.) y SS.SS. con intención de recopilar, indagar y sintetizar la evidencia cualitativa, cuantitativa y mixta en torno a esta relación. Se realiza una investigación primaria que explora las temáticas que enfocan los estudios elegidos desde las bases de datos WOS, Scopus y 1finder (carácter complementario). Se evalúa la calidad de los hallazgos con una síntesis de evidencia cualitativa, cuantitativa y mixta, basada en el método Mixed-Methods Appraisal Tool. En cuanto a los resultados, por un lado, destacar que existe una mayoría de estudios con diseño cualitativo (n = 18) de un total de 23 estudios incluidos en la revisión, otros artículos comprenden diseños de estudios cuantitativos (n = 3) y mixtos (n = 2). Por otro lado, EE.UU. protagoniza el primer puesto como país objeto de estudio de estas obras (n = 6) y también las ciudades de gran tamaño poblacional (n = 13). Por último, reseñar que existe un diferente desarrollo de los artículos en los diferentes países con respecto a las PP.UU. centradas en los SS.SS., una diversidad temática influenciada por el concepto de gestión urbana.

Summary:. Bilateral facial paralysis is a challenging situation requiring complex management. Surgical treatment can include nerve transfers, mainly masseter-to-facial, or muscle transfers, gracilis free flap, or temporalis transposition. Deciding on the surgical option depends on the duration of the paralysis and the feasibility of facial muscles. We present the case of a 10-year-old child with permanent bilateral facial paralysis after brainstem tumor surgery. The patient was treated with bilateral simultaneous hypoglossal-to-facial transfer followed by bilateral simultaneous masseter-to-facial 12 months later. After 23 months of follow-up and specific physical therapy, she has good and symmetric resting tone, complete eye closure, moderate bilateral smile excursion, mild lip pucker movement, and good oral competence. The combination of these two nerve transfers, when possible, gives the opportunity of restoring movement taking the best of each technique, with acceptable results and no significant clinical deficits in the donor sites.

Abstract Background Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high‐risk alterations such as del(11q)/ATM‐mutations and del(17p)/TP53‐mutations have not been established. Methods We integrated next‐generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response. Results Targeted sequencing analysis of the co‐occurrence of high‐risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co‐occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9‐edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition. Conclusions Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.

Purpose: To compare performance of visual and quantitative analyses for detecting myocardial ischaemia from single- and dual-energy computed tomography (CT) in patients with suspected coronary artery disease (CAD). Methods: Eighty-four patients with suspected CAD were scheduled for dual-energy cardiac CT at rest (CTA) and pharmacological stress (CTP). Myocardial CT perfusion was analysed visually and using three parameters: mean attenuation density (MA), transmural perfusion ratio (TPR) and myocardial perfusion reserve index (MPRI), on both single-energy CT and CT-based iodine images. Significant CAD was defined in AHA-segments by concomitant myocardial hypoperfusion identified visually or quantitatively (parameter

RESUMEN Introducción: La prueba de tolerancia de comida mixta es considerada la prueba de oro para la medición de la producción de insulina endógena en pacientes con diabetes tipo 1. Objetivo: Determinar la utilidad de la prueba de tolerancia de comida mixta con Nutrial I para evaluar la función de las células β en diabéticos tipo 1 de diagnóstico reciente y la relación de esa función con algunas características clínicas y bioquímicas. Métodos: Se estudiaron variables bioquímicas como la glucemia, hemoglobina glucosilada (HbA1c), péptido C y fracciones lipídicas. La prueba de tolerancia de comida mixta con Nutrial I se aplicó a 18 sujetos con diabetes tipo 1 de diagnóstico reciente y a 8 voluntarios con edades comprendidas entre 19 y 35 años. El consumo del suplemento Nutrial I se calculó según el peso del paciente. Se obtuvieron muestras para glucemia y péptido C a los -10, 0, 30, 60, 90 y 120 minutos. Resultados: Se observaron concentraciones elevadas de glucemia y disminuidas de péptido C durante la prueba de tolerancia de comida mixta en los diabéticos tipo 1 de diagnóstico reciente, en comparación con los voluntarios, así como, diferencias en las áreas bajo la curva de péptido C (AUC-pc) (p= 0,001). En los diabéticos tipo 1 de diagnóstico reciente se evidenció una correlación negativa entre el AUC-pc con los niveles de glucemia en ayunas (r= -0,747; p ( 0,0001) y la HbA1c (r= -0,535; p= 0,022). Por el contrario, se encontró una correlación positiva entre el AUC-pc y el péptido C en ayunas (r= 0,722; p= 0,001). El AUC-pc después de la prueba de tolerancia de comida mixta es mayor en los sujetos con glucemia en ayunas si GA < 7 mmol/L con respecto a los sujetos con glucemia en ayunas ( 7 mmol/L (p= 0,012). Conclusiones: El empleo del Nutrial I en la prueba de tolerancia de comida mixta fue útil en la evaluación de la función de las células β en diabéticos tipo 1 de diagnóstico reciente. Los valores bajos de glucemia en ayunas durante esta prueba son marcadores indirectos de una función residual de células ( más conservada en los diabéticos tipo 1 de diagnóstico reciente.

Novedades editoriales para los estudios de las mujeres y del género publicados por el CIS. How to observe morals and manners de Harriet Martineau y la traducción de The women founders. Sociology and Social theory 1830-1930 de Patricia Madoo Lengerman y Jill Niebrugge-Brantley.

Los bajos resultados en I+D+i en Canarias, si se los compara con las medias nacionales y europeas, pueden explicarse a través de un análisis institucional de su sistema de innovación. En este artículo se realiza un diagnóstico del sistema regional de I+D+i de Canarias desde una perspectiva sociológica. Se trata de explicar las barreras institucionales a la innovación en una región caracterizada por la terciarización de la economía con escasa implantación industrial, compuesta principalmente de microempresas. Se argumenta que las microempresas, como agente innovador potencial, tienen un limitado acceso a los recursos públicos para la I+D+i en las Islas, por lo que se aboga por una reorientación de las políticas públicas. English The low innovation performance in the Canary Islands, in comparison with national and European scores, can be explained by an institutional analysis of the regional innovation system. In this paper, a sociological approach of such an analysis is presented with the aim of identifying the institutional barriers to innovation in a region with a dependent service economy with little industrial roots, that is mainly composed by micro firms. It is argued that micro firms, as a potential innovative agent, have limited access to public resources for research, development and innovation. Therefore, a reorientation of public policies is suggested.

Background: Dysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g. AR-v7/sst5TMD4/etc.) is associated to prostate-cancer (PCa) aggressiveness and/or castration-resistant PCa (CRPC) development, whether the molecular reason behind such phenomena might be linked to a dysregulation of the cellular machinery responsible for the splicing process [spliceosome-components (SCs) and splicing-factors (SFs)] has not been yet explored. Methods: Expression levels of 43 key SCs and SFs were measured in two cohorts of PCa-samples: 1) Clinically-localized formalin-fixed paraffin-embedded PCa-samples (n = 84), and 2) highly-aggressive freshly-obtained PCa-samples (n = 42). Findings: A profound dysregulation in the expression of multiple components of the splicing machinery (i.e. 7 SCs/19 SFs) were found in PCa compared to their non-tumor adjacent-regions. Notably, overexpression of SNRNP200, SRSF3 and SRRM1 (mRNA and/or protein) were associated with relevant clinical (e.g. Gleason score, T-Stage, metastasis, biochemical recurrence, etc.) and molecular (e.g. AR-v7 expression) parameters of aggressiveness in PCa-samples. Functional (cell-proliferation/migration) and mechanistic [gene-expression (qPCR) and protein-levels (western-blot)] assays were performed in normal prostate cells (PNT2) and PCa-cells (LNCaP/22Rv1/PC-3/DU145 cell-lines) in response to SNRNP200, SRSF3 and/or SRRM1 silencing (using specific siRNAs) revealed an overall decrease in proliferation/migration-rate in PCa-cells through the modulation of key oncogenic SVs expression levels (e.g. AR-v7/PKM2/XBP1s) and alteration of oncogenic signaling pathways (e.g. p-AKT/p-JNK). Interpretation: These results demonstrate that the spliceosome is drastically altered in PCa wherein SNRNP200, SRSF3 and SRRM1 could represent attractive novel diagnostic/prognostic and therapeutic targets for PCa and CRPC. Keywords: Prostate cancer, Splicing, Spliceosome, SNRNP200, SRSF3, SRRM1, Therapeutic target

Este artículo presenta los resultados de un estudio cuyo objetivo fundamental es conocer la presencia que tienen las tecnologías en el tiempo libre de los jóvenes, usos y motivaciones de éstas, así como situaciones de violencia online que conocen en sus entornos más próximos. Concretamente se ha utilizado un diseño descriptivo tipo encuesta, a partir de un cuestionario diseñado ad hoc. La muestra se compone de 287 estudiantes de Educación Secundaria Obligatoria de entre 13 y 17 años (51,9% de chicos y 48,1% de chicas). Los resultados muestran una fuerte presencia de la tecnología en el ocio, la comunicación y en las relaciones entre pares. Asimismo, se evidencia la existencia de violencia online a través del móvil y redes sociales, ejercida en forma de amenazas, violencia verbal y psicológica; aspecto que en las relaciones amorosas se realiza a través del control e influencia sobre el entorno de amistades de la pareja. En la discusión de resultados se plantea que los adolescentes realizan un uso de la tecnología orientada a la búsqueda del placer y la satisfacción inmediata. La instrumentalización del uso nos alerta sobre la necesidad de educar y sensibilizar desde todos los ámbitos en la formación de ciudadanos conscientes, críticos y responsables para desenvolverse en escenarios digitales.

Abstract Background In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype. Methods One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models. Results The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p

Resumen: La hipertensión pulmonar tromboembólica crónica se considera el único tipo de hipertensión pulmonar con un tratamiento quirúrgico potencialmente curativo. Aun hoy está infradiagnosticada o con frecuencia diagnosticada tardíamente, comportando un empeoramiento del pronóstico. La hipertensión pulmonar tromboembólica crónica se presenta con síntomas poco específicos y los médicos de atención primaria pueden no ser conscientes de su presencia o del potencial tratamiento. El tratamiento médico actual es, en el mejor de los casos, paliativo. La endarterectomía pulmonar ofrece la única posibilidad de mejora sintomática y pronóstica, siendo curativa en la mayoría de los casos a corto y a largo plazo. Por lo tanto, no solo la identificación de la enfermedad puede ser difícil y tardía sino que incluso después de que el diagnóstico se haya establecido, la evaluación de la operabilidad puede ser un reto. La operabilidad se basa en la estimación preoperatoria de la clasificación quirúrgica y de la probable resistencia vascular pulmonar postoperatoria, las cuales determinan el riesgo de la intervención y el posible resultado. Este complejo procedimiento que va desde la caracterización de la enfermedad a la intervención quirúrgica pasando por todo el proceso decisional, requiere una colaboración multidisciplinar de expertos en hipertensión pulmonar, con un equipo quirúrgico dedicado a este campo y con protocolos bien precisos. En nuestro centro, hemos construido un equipo especializado que incluye radiólogos, cardiólogos, cirujanos cardiacos, anestesistas/intensivistas y fisioterapeutas, que no solo ha permitido obtener resultados quirúrgicos comparables a centros europeos de más alto volumen, sino que también ha permitido desarrollar e implementar otras opciones terapéuticas como la angioplastia pulmonar con balón, dedicadas a los pacientes de alto riesgo descartados para la cirugía.En el siguiente artículo presentamos una revisión sobre la actualidad en este campo y al mismo tiempo ponemos de ejemplo nuestra experiencia como centro en la gestión de la hipertensión pulmonar tromboembólica crónica a través de un equipo multidisciplinar especializado. Abstract: Chronic thromboembolic pulmonary hypertension is considered the only type of pulmonary hypertension with a potentially curative surgical treatment. Even today it is under-diagnosed or often diagnosed late with a worsening of the prognosis. Chronic thromboembolic pulmonary hypertension presents with nonspecific symptoms and general practitioners may not be aware of the condition or potential for treatment. Current medical treatment is, at best, palliative. Pulmonary endarterectomy offers the only possibility of symptomatic and prognostic improvement, being curative in most cases in the short and long term. Not only the identification of the pathology can be difficult and delayed, moreover after the diagnosis has been established, the estimation of operability can be challenging. The operability is based on the preoperative estimation of postoperative surgical classification and probable pulmonary vascular resistance, which determine the risk of intervention and the probable outcome. This complex procedure that includes, characterization of the pathology, the surgical intervention going through the whole decision process requires a multidisciplinary collaboration of experts in pulmonary hypertension, with a dedicated surgical team, and with very precise protocols. At our center, we have built a team of dedicated specialists including radiologists, cardiologists, cardiac surgeons, anesthesiologists and physiotherapists. Together, not only we have been able to obtain surgical results comparable to higher European centers, but also, to develop and implement other therapeutic options such as pulmonary angioplasty with balloon, dedicated to patients at high risk and discarded for surgery.In the present paper, we present a review of the pathology and, as an example, our single center experience with a multidisciplinary and dedicated management of chronic thromboembolic pulmonary hypertension patients, specifically diagnosis, pulmonary endarterectomy indication, protocols and results. Palabras clave: Hipertensión pulmonar, Parada de círculo hipotérmica, Endarterectomía, Keywords: Pulmonary hypertension, Deep hypothermic circulatory arrest, Endarterectomy

In recent times, the history of education has expanded its scope of study with the use of new sources, such as teaching practice reports of primary school would-be teachers. In order to know the reality of the public school system in post-war Spain, we focus on the analysis of an unpublished collection of teaching practice reports, written between 1936 and 1949, stored in the archives of the University of La Laguna (Tenerife, Canary Islands). This analysis allows us to affirm that there are aspects of classroom everyday life that surpass the archetypes of the Francoist school and its school culture, determined by its ideological impositions and its legal norms. It is confirmed that there was certain continuity in the pedagogical renewal of education at the time, a fact that shows the distance that separates what is prescribed by legislation and what actually happens within the school classroom.

Acute aortic syndrome (AAS) comprises a range of interrelated conditions caused by disruption of the medial layer of the aortic wall, including aortic dissection, intramural haematoma and penetrating aortic ulcer. Since mortality from AAS is high, a prompt and accurate diagnosis using imaging techniques is paramount. Both transthoracic (TTE) and transoesophageal echocardiography (TEE) are useful in the diagnosis of AAS. TTE should be the first imaging technique to evaluate patients with thoracic pain in the emergency room. Should AAS be suspected, contrast administration is recommended when images are not definitive. TEE allows high-quality images in thoracic aorta. The main drawback of this technique is that it is semi-invasive and the presence of a blind area that limits visualisation of the distal ascending aorta near. TEE identifies the location and size of the entry tear, secondary communications, true lumen compression and the dynamic flow pattern of false lumen. Although computed tomography (CT) is the most used imaging technique in the diagnosis of AAS, echocardiography offers complementary information relevant for its management. The best imaging strategy for appropriately diagnosing and assessing AAS is to combine CT, mainly ECG-gated contrast-enhanced CT, and TTE. Currently, TEE tends to be carried out in the operating theatre immediately before surgical or endovascular therapy and in monitoring their results. The aims of this review are to establish the current role of echocardiography in the diagnosis and management of AAS based on its advantages and limitations.

Background: Left atrial deformation (LAD) parameters are new markers of atrial structural remodelling that seem to be affected in atrial fibrillation (AF) and atrial flutter (AFL). This study aimed to determine whether LAD can identify patients with a higher risk of thrombosis and unsuccessful electrical cardioversion (ECV). Methods: Retrospective study including 56 patients with AF or AFL undergoing ECV, with previous transthoracic (TTE) and transoesophageal echocardiography (TEE) studies. Echocardiographic parameters analysed were as follows: left ventricle function, left atrium (LA) dimensions, LAD parameters (positive and negative strain peaks), left atrial appendage (LAA) filling and emptying velocities and the presence of thrombi. Strain values were analysed according to thrombotic risk and success of ECV. Results: Lower mean values of peak-positive strain (PPS) in patients with prothrombotic velocities (

La Universidad de Sevilla (España) ofrece nuevos servicios online entre los que se encuentran los de apoyo y orientación. El servicio de e-orientación está articulado a través de diferentes portales que recogen la información de las actuaciones de asesoramiento ofertadas, así como proporciona orientación online en mucho de los servicios. El éxito de estos servicios dependerá, en gran medida, del grado de participación del alumnado y del aprovechamiento de estos recursos. Por este motivo, el objetivo de este estudio es conocer el grado de conocimiento, utilización, valoración y expectativas de los estudiantes con respecto a los servicios de orientación online que la institución les ofrece. La población objeto de estudio se compone de 57624 universitarios que corresponde al número de alumnos matriculados en Grados en la Universidad de Sevilla. La muestra final se compone de 413 estudiantes de 68 titulaciones diferentes con un nivel de confianza del 95% y asumiendo un error muestral del 5%. La recogida de datos se ha realizado mediante un cuestionario telemático diseñado ad-hoc. Los datos revelan un desconocimiento profundo por parte de los estudiantes de los servicios de e-orientación que se ofrecen. Este fenómeno genera niveles muy bajos de utilización y valoración, centrándose la mayoría de las interacciones en simples consultas de información. Sin embargo, el alumnado muestra una predisposición favorable hacia la mejora y ampliación de los entornos digitales actuales. Los hallazgos obtenidos podrían considerarse como un indicador del nivel de alfabetización digital que poseen los universitarios.

La formación del profesorado constituye un soporte básico del sistema educativo. Nuestro objetivo consiste en estudiar el modelo de formación del profesorado de Educación General Básica que ha existido en España desde la configuración de este nivel educativo con la Ley General de Educación (1970) hasta la promulgación de la Ley de Ordenación General del Sistema Educativo (1990). En dicho análisis se consideran algunas cuestiones básicas de la formación así como la variable de género. Hemos empleado la metodología de análisis histórico educativo, siguiendo el procedimiento habitual de este diseño metodológico. El estudio histórico educativo nos permitió conocer la política educativa para la formación del profesorado y vislumbrar las diferencias de género en el contexto social y político del tardofranquismo en tránsito a la monarquía constitucional. Con estas aportaciones contribuimos a la reflexión sobre los programas de formación docente.

The virtuous relationship among education, citizenship and democracy is paramount in contemporaneity. This controversial conceptual triangle is associated to the origin of political education and to the development of national educational systems that aim at training citizens who are essential to the support and advance of democracy. Education to citizenship has been referred to in the political and educational sectors with different definitions, names and purposes, but there is no shared definition regarding its aims, theoretical applications, contents, pedagogical models and objectives.Currently, within the context of the processes of democratization in Latin America and Mexico, the concept of citizenship is being redefined and its role in the education of citizens, both old and new, is being revalued. At the same time, new educational and social actors are emerging, who, with different initiatives, tend to train more active citizens who will participate in public life, having an interested impact on it, which will go beyond participation in elections.This essay will not only reflect on what has been argued so far, but it also aims at highlighting a concept of substantive citizenship based on rights and responsibilities, which requires individuals to be educated to participate and develop the necessary competences to put their rights as human beings and citizens into practice.

Introducción y objetivos: El Grupo de Trabajo en Reparación Valvular de la Sociedad Española de Cirugía Torácica y Cardiovascular presenta el cuarto Registro anual de actividad en cirugía reparadora de las válvulas mitral, aórtica y tricúspide realizada en España durante el año 2014. Material y métodos: La recogida de datos se realizó mediante cuestionario on-line, de forma retrospectiva, voluntaria, anónima y no auditada. Se detalla la actividad reparadora y de recambio valvular por grupos. En el grupo mitral se clasificaron las intervenciones de acuerdo con su etiología y se recogieron como variables mortalidad y riesgo quirúrgico, tanto en el grupo total como en pacientes electivos. Resultados: Veintisiete centros participaron en la elaboración de registro. El 70% aportó datos sobre mortalidad. El número de procedimientos de reparación global fue del 22% (36,6% mitrales, 3,5% aórticas y 92,5% tricúspides). La cirugía mitral reparadora fue posible en el 60% de las valvulopatías degenerativas, isquémicas y funcionales, y solo en el 2,8% de las reumáticas. La mortalidad global fue del 1,95%. El porcentaje de reparaciones aórticas oscila por grupos entre el 0 y el 48%. La cirugía reparadora tricúspide se mantiene en cifras similares a años previos. Las técnicas miniinvasivas fueron empleadas en el 3,4% de las cirugías mitrales y el 11,8% de las aórticas. Conclusiones: La actividad reparadora valvular mitral está actualmente consolidada en España, siendo especialmente infrecuente cuando la etiología de la valvulopatía es reumática. La cirugía reparadora aórtica difiere mucho entre grupos y parece encontrarse estabilizada.

La Ley General de Educación (1970) elevó a rango universitario a los estudios profesionales de magisterio. Las escuelas normales perdieron su identidad al integrarse en la Universidad como Escuelas Universitarias de Formación del Profesorado de Enseñanza General Básica. En el programa de estudios, en sintonía con el currículum escolar, se combinaba la formación de maestro generalista, capacitado para impartir enseñanzas en la primera etapa de la Enseñanza General Básica y la de maestros especialistas, para cada una de las áreas establecidas en la segunda etapa (Ciencias, Ciencias Sociales y Lengua Española e Idiomas Modernos). En este artículo se hace un recorrido por lo que ha sido la formación inicial de los maestros de Educación Primaria en España, particularmente en ciencias. Se analizan aspectos como las necesidades profesionales, las demandas de la sociedad de la época y los currículos. La metodología consiste en analizar los programas educativos, la legislación y la literatura cientíica. Inicialmente, hemos realizado una revisión de fuentes secundarias, de las publicaciones referidas al tema que nos ocupa. Se han contrastado las percepciones y propuestas para el aprendizaje cientíico que se han realizado desde ámbitos educativos. Los resultados muestran la evolución de las ciencias en la formación de maestros y en el currículum de enseñanza primaria.

Background: The t(12;21)(p13;q22), which fuses ETV6 and RUNX1 genes, is the most common genetic abnormality in children with B-cell precursor acute lymphoblastic leukaemia. The implication of the fusion protein in leukemogenesis seems to be clear. However, its role in the maintenance of the disease continues to be controversial. Methods: Generation of an in vitro ETV6/RUNX1 knock out model using the CRISPR/Cas9 gene editing system. Functional characterization by RNA sequencing, proliferation assays, apoptosis and pharmacologic studies, and generation of edited-cell xenograft model. Results: The expression of ETV6/RUNX1 fusion gene was completely eliminated, thus generating a powerful model on which to study the role of the fusion gene in leukemic cells. The loss of fusion gene expression led to the deregulation of biological processes affecting survival such as apoptosis resistance and cell proliferation capacity. Tumour cells showed higher levels of apoptosis, lower proliferation rate and a greater sensitivity to PI3K inhibitors in vitro along as a decrease in tumour growth in xenografts models after ETV6/RUNX1 fusion gene abrogation. Conclusions: ETV6/RUNX1 fusion protein seems to play an important role in the maintenance of the leukemic phenotype and could thus become a potential therapeutic target.

To explore and document the experiences and values of spouse caregivers of stroke survivors. To gain more in-depth knowledge of how the act of caring and the adaption process affects caregiving spouses.Phenomenological, qualitative study. This study included spouses of stroke survivors who also served as primary caregivers. Individual, semi-structured, in-depth interviews were conducted, transcribed, and analysed using a thematic content analysis as proposed by Giorgi. Data was analysed and managed using Atlas-ti (version 7.0). This study was approved by our institution´s Complejo Hospitalario de Caceres Ethics and Research Committee.Spouse caregivers of stroke survivors undergo a process of disruption in their private lives and relationships, marked by their caregiving duties. The experiences of spouses caring for stroke survivors is condensed into topics and subtopics: "Caregiving and that´s all" summarizes the sense of having no life horizons and also caregiver impossibility of moving away from caring role. Otherwise, "Breaking the couple´s life together" enlightens the further consequences of stroke in couples shared live biography, which needs to be understood and rebuilt. Finally, "Going through the (non) loss alone" alludes to how spouses reinterpret meaning of loss, which is not appreciated by others and that refers to the balance between stroke survival and any acquired global disability.A comprehensive approach to the couple (family), from a psycho-socio-emotional and relational perspective, is essential for ensuring adequate quality of life for people who suffered a stroke as well as their caregivers. Spouses-caregivers must be considered as individuals living a transition process due to their unexpected disrupting change, which nurses should address through a comprehensive and integrated approach focused on transition care. Care resources must be adapted to the interpretation that the spouses have of their caregiving role and their relationship with the different components of the caregiving process.