The projection of images in the Spanish secondary school classrooms in the first third of the 20th century

In the context of the research project ‘Dynamics of Educational and Scientific Renewal in Secondary School Classrooms (1900-1936): An Iberian perspective’. (HAR 2014-54073) it has been developed an empi-rical study using the methodology of Content Analysis. This methodology has been applied to the set of visual messages with divulgative character was projected all over the Historical High School in Spain. The results of the studies reveal relevant aspects of the role that mentioned elements of material culture had in the transformation of the science teaching in the Secondary School Classrooms in the First Third of the 20thEn el contexto del proyecto de investigación ‘Dinámicas de renovación educativa y científica en las aulas de bachillerato (1900-1936): una perspectiva ibérica’ (HAR 2014-54073) se ha desarrollado un estudio de análisis de contenido aplicado al conjunto de mensajes visuales de carácter divulgativo proyectados en los institutos históricos de bachillerato en España. Los resultados del estudio desvelan aspectos relevantes del papel que dichos elementos de la cultura material tuvieron en la transformación de la enseñanza científica en las aulas españolas de educación secundaria en el primer tercio del siglo XX

An innovative tool for intraoperative electron beam radiotherapy simulation and planning: description and initial evaluation by radiation oncologists

The lack of specific treatment planning tools limits the spread of Intraoperative Electron Radiation Therapy. An innovative simulation and planning tool is presented. Applicator positioning, isodose curves, and doseevolume histograms can be estimated for previously segmented regions to treat/protect. Evaluation by three radiation oncologists on 15 patients showed high parameter agreement in nine cases, demonstrating the possibilities in cases involving different anatomical locations, and identifying the importance of specialized surgical input in the preplanning process.Supported by grants PI08/90473, IPT 300000 2010 3, ARTEMIS S2009/DPI 1802(CAM), TEC2010 21619 C04 01, PI09/90568, ERD Funds.Publicad

Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bor tezomib and dexamethasone

Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients.This work was in part funded by the Spanish ISCIII-FIS (PI 15/0067 and PI15/02156) and FEDER, the Spanish RTICC (RD12/0036/0058), "Asociación Española Contra el Cancer" (AECC, GCB120981SAN), the regional Council from “Castilla y León” (GRS 1175/A/15 and FIC335U14) and a research grant from Pharmamar SAU. MMS were also supported by the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León, Spain. A-A López-Iglesias was supported by a grant from the Spanish Society of Hematology and Hemotherapy.Peer Reviewe

Clinical and immunological study of tofacitinib and baricitinib in refractory blau syndrome: case report and literature review

Blau syndrome (BS) is an autoinflammatory disorder characterized by non-caseating granulomatous dermatitis, arthritis, and uveitis. We present a case of refractory and severe BS that was treated with the Janus kinase inhibitors (JAKINIBS), Tofacitinib (TOFA) and then Baricitinib (BARI). Our aim was to describe the clinical and immunological outcomes after treatment with JAKINIBS. Blood tests and serum samples were obtained during follow-up with TOFA and BARI. We assessed their effects on clinical outcomes, acute phase reactants, absolute lymphocyte counts (ALCs), lymphocyte subset counts, immunoglobulins, and cytokine levels. A review of the literature on the use of JAKINIBS for the treatment of uveitis and sarcoidosis was also conducted. TOFA led to a rapid and maintained disease control and a steroid-sparing effect. A decrease from baseline was observed in ALC, CD3+, CD4+, CD8+, and natural killer (NK) cell counts. B-cells were stable. Serum levels of interleukin (IL)-4 and tumor necrosis factor alpha (TNF-?) increased, whereas IL-2, IL-6, IL-10, and IL-17 maintained stable. TOFA was discontinued after 19 months due to significant lymphopenia. The initiation of BARI allowed maintaining adequate control of disease activity with an adequate safety profile. The literature review showed seven patients with uveitis and five with sarcoidosis treated with JAKINIBS. No cases of BS treated with JAKINIBS were found. We report the successful use of JAKINIBS in a patient with refractory and severe BS.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by Redes Temáticas de Investigación Cooperativa en Salud (RETICS) Program, RD16/0012 Red de Investigación en Inflamación y Enfermedades Reumáticas (RIER) from ISCIII from "Instituto de Salud Carlos III" (ISCIII) (Spain)

Innate and adaptive immune assessment at admission to predict clinical outcome in covid-19 patients

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27-CD28-, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27-CD28-, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease.Funding: This work was partially supported by the Cantabrian Government, grant number 2020UIC22-PUB-001, and by Instituto de Salud Carlos III, grant number COV20/00170

Proyecto Orla 2.0. Curso 2019 La fotografía como herramienta para la innovación docente, la investigación etnográfica, la intervención social y la creación cultural

Memoria ID-072. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2018-2019

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

[EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models. Mechanisms of this synergistic combination were dissected by gene expression profiling, immunostaining, cell cycle and short interfering ribonucleic acid studies. Filanesib showed in vitro, ex vivo, and in vivo synergy with pomalidomide plus dexamethasone treatment. Importantly, the in vivo synergy observed in this combination was more evident in large, highly proliferative tumors, and was shown to be mediated by the impairment of mitosis transcriptional control, an increase in monopolar spindles, cell cycle arrest and the induction of apoptosis in cells in proliferative phases. In addition, the triple combination increased the activation of the proapoptotic protein BAX, which has previously been associated with sensitivity to filanesib, and could potentially be used as a predictive biomarker of response to this combination. Our results provide preclinical evidence for the potential benefit of the combination of filanesib with pomalidomide and dexamethasone, and supported the initiation of a recently activated trial being conducted by the Spanish Myeloma group which is investigating this combination in relapsed myeloma patients.Array BioPharma, the Spanish ISCIII-FIS and FEDER, the Spanish RTICC, Spanish Association Against Cancer (AECC) and the Regional Council of Castilla y León (Consejería de Medicina y Educación)

C3G promotes a selective release of angiogenic factors from activated mouse platelets to regulate angiogenesis and tumor metastasis

[EN]Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis. Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3GΔCat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth. In addition, transgenic C3G expression in platelets greatly increased mouse melanoma cells metastasis. Moreover, immunofluorescence microscopy showed that the pro-angiogenic factors VEGF and bFGF were partially retained into α-granules in thrombin- and ADP-activated mouse platelets from both, C3G and C3GΔCat transgenic mice. The observed interaction between C3G and Vesicle-associated membrane protein (Vamp)-7 could explain these results. Concomitantly, increased platelet spreading in both transgenic platelets upon thrombin activation supports this novel function of C3G in α-granule exocytosis. Collectively, our data point out to the co-existence of Rap1GEF-dependent and independent mechanisms mediating C3G effects on platelet secretion, which regulates pathological angiogenesis in tumors and other contexts. The results herein support an important role for platelet C3G in angiogenesis and metastasis

Aula virtual de Máster en Profesor de Secundaria

Memoria ID-0322. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Hacia la innovación en la gestión y docencia en las asignaturas del practicum del MUPES (Máster Universitario en Profesor de Educación Secundaria Obligatoria, Bachillerato, Formación Profesional y Enseñanzas de Idiomas)

Memoria ID-0129. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017