Doña María de Padilla, de personaje histórico a figura literaria

Doña María de Padilla, personaje del medievo, es el eje de una investigación que profundiza, inicialmente, en su vertiente histórica para enlazar con la literaria. El estudio de su genealogía, su itinerario, su escudo de armas, sus señoríos y heredades, más el núcleo de dotación que estableció en torno al Monasterio de Astudillo (fundado junto a Pedro I de Castilla), con la implicación de distintas mujeres de su familia, ofrecen un perfil histórico de su persona resolutivo y soberano. Por otra parte, el análisis de su presencia constante como figura literaria desde los siglos XIV al XIX destaca la importancia y ascendencia del romancero, tanto en la construcción del perfil terrible que se le adjudicó, como su influencia posterior en otros géneros: teatro, poesía, romance o copla. Así mismo, el interés despertado por el personaje de doña María traspasó fronteras, encontrando un eco especial en la literatura francesa, en las etapas y géneros analizados. PALABRAS CLAVE: Crónicas, Doña María de Padilla, Don Pedro, Genealogía, Itinerario, Escudo de Armas, Heredades, Romancero, Teatro, Copla

Derivados de 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso en el tratamiento de enfermedades neurodegenerativas

Derivados de 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso en el tratamiento de enfermedades neurodegenerativas. Compuestos químicos derivados del sistema heterocíclico 1,4,5-dibenzo[b,f]tiadiazepinas 5,6-dihidro y su uso como composiciones farmacéuticas para el tratamiento de enfermedades del sistema nervioso central, provocadas por una serie de procesos incluidos en lo que genéricamente se denomina neurodegeneración, en concreto para el tratamiento de Alzheimer, enfermedad de Parkinson o enfermedad de Huntington.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Autónoma de MadridB1 Patente sin examen previ

Estructuras y rendimientos de madera resultantes de la aplicación de dos intensidades de raleo en un tallar de diez años de edad de sauce americano (Salix babylonica var. sacramenta) en el Delta del Paraná

La silvicultura del sauce americano (Salix babylonica var. sacramenta) presenta aspectos poco estudiados, como el manejo de la densidad mediante raleos. Los objetivos de este trabajo fueron: a- caracterizar la estructura de un bosque de tallar de sauce americano de 10 años sin conducción previa, b- analizar el estado de la densidad mediante el índice de densidad de rodal de Reineke (IDR), c- evaluar las estructuras resultantes de la aplicación de dos intensidades de raleo y d- estimar los rendimientos de madera para triturado y para uso potencial en bioenergía obtenidos en estos raleos. Los estudios se llevaron a cabo en un rodal implantado con 1680 plantas/ha, cortado y regenerado por rebrote en 1998. Se estableció un ensayo con tres tratamientos: rebrote sin raleos (T), raleo por lo bajo dejando 1 fuste por cepa (R1) y raleo por lo bajo dejando hasta 2 fustes por cepa (R2). En los raleos la madera (viva y muerta) se elaboró según dos destinos: molienda (trozas de 2,2 m de largo y 7,5 cm mínimo en punta fina) y biomasa leñosa utilizable en la producción de bioenergía. Luego se estimó la biomasa remanente en pie (t/ha) mediante ecuaciones de predicción a partir del DAP de los fustes vivos. Los fustes vivos del rodal sin manejar tenían: DAP medio= 10,5 cm; altura media= 12 m; área basal media= 23,8 m2/ha; asimismo se encontró un 42% de cepas vivas respecto de la plantación inicial, y 3688 fustes muertos en pie por hectárea. El tratamiento T tuvo un IDR medio de 548, mientras que en R1 el IDR alcanzado fue de 286 y en R2 fue de 387. Mediante R1 se obtuvo un rendimiento medio total de 70,5 t/ha de biomasa leñosa (40,4 t/ha aptas para molienda; 29,1 t/ha para bioenergía) en tanto que con R2 el rendimiento fue de 28,9 t/ha (12,7 t/ha molienda; 16,2 t/ha bioenergía). La biomasa remanente en pie fue estimada en 155,8 t/ha totales para T (87,3 t/ha molienda; 68 t/ha bioenergía), en 89,6 t/ha para R1 (51,8 t/ha molienda; 36,1 t/ha bioenergía) y en 112 t/ha para R2 (66 t/ha molienda; 46,5 t/ha bioenergía). La estructura del rodal sin raleos indicó un estado de plena ocupación de sitio y la ocurrencia de altos niveles de competencia intraespecífica. El tratamiento R1 sería preferible a R2, ya que permite obtener mayores rendimientos y lograr un IDR en torno al 35% del IDR máximo.Facultad de Ciencias Agrarias y Forestale

Interlaboratory analytical validation of a Next-generation sequencing strategy for clonotypic assessment and minimal residual disease monitoring in multiple myeloma

[Context]: Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited. [Objective]: To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma. [Design]: The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility. [Results]: Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF (R2 > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing. [Conclusions]: Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures. Multiple myeloma (MM) is a plasma-cell dyscrasia characterized by the accumulation of plasma cells in the bone marrow that produces an excess of clonal immunoglobulins (M-protein or monoclonal component).1 New treatment approaches have increased the number of patients achieving complete response (CR),2–5 progressively improving progression-free and overall survival rates in the last 10 years.6–11 Nonetheless, the presence of low levels of drug-resistant cells (known as minimal residual disease, MRD)12–14 that remain undetected by conventional serologic and morphologic methods explains frequent relapses with this disease, which is still considered an incurable illness.Minimal residual disease is currently considered one of the most informative prognostic parameters, since those patients with undetectable disease have shown prolonged survival rates as compared with MRD-positive patients,15–17 and this difference is still significant even when patients achieving only stringent complete response (sCR) are taken into account.18 The International Myeloma Working Group (IMWG) defined MRD positivity as the persistence of clonal malignant plasma cells assessed with a sensitivity of at least 10−5 (1 malignant cell per hundred thousand normal cells)19 ; therefore, MRD should be monitored with only highly sensitive methods. To date, 3 different approaches have been tested for MRD monitoring in hematologic malignancies: immunophenotypic (multiparametric flow cytometry [MFC]),20 molecular (quantitative polymerase chain reaction [PCR], next-generation sequencing [NGS], digital PCR),21–23 and imaging tools (positron emission tomography–computed tomography; magnetic resonance imaging).24,25 However, in MM standardization has been achieved only for MFC26 and NGS.27,28 As a result, the IMWG recommended the use of highly sensitive, standardized flow and sequencing approaches,19 including EuroFlow's next-generation flow (NGF)29 and Adaptive Biotechnologies' ClonoSEQ solutions (Adaptive Biotechnologies, Seattle, Washington). NGF is a 2-tube, 8-color flow assay that allows the simultaneous analysis of 10 million cells, providing a sensitivity of around 2·10−6.This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01956, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010). García-Álvarez, Prieto-Conde, and Jiménez were supported by the Fundación Española de Hematología y Hemoterapia (FEHH, cofunded by Fundación Cris in the latter case), Medina by the European Social Fund through the University of Salamanca and the ISCIII (FI19/00320), and Sarasquete by the ISCIII (CPII18/00028). All Spanish funding is cosponsored by the European Union FEDER program

Increased risk of MAFLD and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors

ackground & Aims There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. Methods Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. Results Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. Conclusions MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.Acknowledgements: The authors report funding support from the Spanish Instituto de Salud Carlos III-FEDER Grant (FIS - PI18/01304) related to this manuscript

Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array

GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) cooperative study group.Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P =.1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment.This work has been partially supported by grants of the Instituto de Salud Carlos III (ISCIII) (CP13/00080), ISCIII (PI12/02311), Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0069) (RD12/0036/0061), Ministerio de Economía y Competitividad/ Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” (Innocampus; CEI‐2010‐1‐0010), Asociación Española Contra el Cancer (GCB120981SAN), and Joan Rodes (JR 14/00016). M.E.S. is supported by the Miguel Servet program (CP13/00080) of the ISCIII (Ministerio de Economía y Competitividad).Peer Reviewe

Homérica: estudiar y vivir el mundo griego

Depto. de Filología ClásicaFac. de FilologíaFALSEsubmitte

Estrategias docentes para el desarrollo de competencias profesionales en la nueva mención de Gestión del Ocio y la Cultura del Grado en Turismo

Memoria ID-0324. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Diseño e implementación de rutas divulgativas STEAM en Madrid: Un proyecto de Aprendizaje-Servicio

Se recoge información sobre el desarrollo de un proyecto de aprendizaje-servicio, implementado en la Universidad Politécnica de Madrid durante el año 2023. Tras introducir esta metodología educativa, se describen el contexto, los objetivos y los resultados del proyecto titulado ‘Madrid a ciencia cierta: Diseño e implementación de rutas guiadas con temática STEAM’. A través del proyecto, un grupo de alumnos y profesores colaboraron en el diseño e implementación de dos rutas divulgativas, en Madrid: ‘Los elementos químicos “españoles”: tres hitos del período de la Ilustración’ y ‘Los “altos del hipódromo”: una zona emblemática de la ‘Edad de Plata’ de la cultura española (1868-1936)’. El trabajo forma parte de la Comunidad ‘Equalitarian Societies: opportunnities for everyone (ES:04E)’, dentro de la comunidad de Universidades europeas EELISA