Título: Cuando yo sea maestra

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma

Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy.This study was supported by grants from: Ministerio de Economía y Competitividad, Fondo de Investigación Sanitaria (PI12/101 to HM; PI12/00775 to PSG; PS09/1786 to MGF and PI13/01258 to AHL), Comunidad de Madrid (S2010/BMD-2336 to HM), Xunta de Galicia (EM2013/042 to MGF), Fundación BBVA (2014-PO010 to MGF) and Ministerio de Economía y Competitividad, Red Temática de Investigación Cooperativa en Cáncer (RD12/0036/0027 to PSG and AHL). PGG was recipient of a “Sara Borell” postdoctoral fellowship, and MdF of a “Miguel Servet” contract from Ministerio de Economía y CompetitividadS

Teachers’ perception of disruptive behaviour in the classrooms

Antecedentes: el fenómeno de la disrupción es cada vez más habitual en las aulas y se asocia específicamente a conductas que dificultan y obstaculizan el proceso de enseñanza-aprendizaje. El objetivo principal de esta investigación consiste en analizar la percepción del profesorado sobre esta cuestión. Específicamente se trata de observar qué valoración dan a las medidas propuestas para mejorar la docencia, examinar qué modalidades de escolarización consideran más idóneas para afrontar la disrupción, determinar sus causas y analizar si existen diferencias según las características del profesorado. Método: 346 participantes respondieron a una escala de conductas disruptivas tipo Likert. La edad media es de 43,47, siendo el 82,9% mujeres y el 13,6% hombres. Resultados: las medidas propuestas para la mejora de la docencia son ampliamente aceptadas, existiendo diferencias en su priorización; la modalidad de escolarización idónea es la de centros ordinarios, existiendo diferencias de opinión, según las características del profesorado; y todas las causas del incremento de problemas son altamente puntuadas, destacando la falta de normas y límites en el entorno familiar. Conclusiones: los profesores demandan mejoras y necesidad de apoyo institucional. Toda reflexión previa sobre cómo mejorar la calidad del sistema educativo podría tener en consideración los resultados de este estudio

Funcionamiento de la integración en la enseñanza según la percepción de los maestros especialistas en Pedagogía Terapéutica

El objetivo central de este estudio es analizar la percepción que tienen los maestros especialistas en Pedagogía Terapéutica acerca de la integración de los alumnos con necesidad de apoyo educativo.Se diferencian distintos colectivos de alumnos. Más específi camente, se trata de conocer cómo los especialistas perciben el rendimiento y la participación de estos estudiantes, así como determinadas actitudes hacia ellos (aceptación, implicación de los compañeros?). También se analiza su opinión acerca de las diferentes medidas que se proponen para mejorar la integración y cuáles son las modalidades de escolarización y de apoyo preferidas. Para alcanzar estos objetivos se ha utilizado un cuestionario tipo Lickert de 114 ítems, más 8 ítems de identifi cación personal. La muestra está compuesta por 106 maestros que trabajan en Asturias, de un total de 406. Los resultados revelan que los maestros no perciben las mismas actitudes en todos los colectivos estudiados. Los alumnos con trastornos de comportamiento son los más rechazados y los que menos expectativas generan en los docentes. El grupo de minorías étnicas necesita mejorar la implicación familiar. Los especialistas demandan más recursos personales y materiales y la mayoría opina que la modalidad de escolarización más conveniente la constituyen los centros ordinarios

Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives

Objective: Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors. Methods and Results: Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by largeconductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR. Conclusions: Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation

Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms

Ruxolitinib is the front-line non-palliative treatment for myelofibrosis (MF). However, a significant number of patients lose or present suboptimal response, are resistant or have unacceptable toxicity. In an attempt to improve response and avoid the adverse effects of this drug, we evaluated the combination of 17 drugs with ruxolitinib in ex vivo models of peripheral blood mononuclear cells from MF patients and cell lines. We found that the combination ruxolitinib and nilotinib had a synergistic effect against MF cells (ΔEC50 nilotinib, -21.6%). Moreover, the addition of prednisone to combined ruxolitinib/nilotinib improved the synergistic effect in all MF samples studied. We evaluated the molecular mechanisms of combined ruxolitinib/nilotinib/prednisone and observed inhibition of JAK/STAT (STAT5, 69.2+11.8% inhibition) and MAPK (ERK, 29.4+4.5% inhibition) signaling pathways. Furthermore, we found that the triple therapy combination inhibited collagen protein and COL1A1 gene expression in human bone marrow mesenchymal cells. Taken together, we provide evidence that combined ruxolitinib/nilotinib/prednisone is a potential therapy for MF, possibly through the anti-fibrotic effect of nilotinib, the immunomodulatory effect of ruxolitinib and prednisone, and the anti-proliferative effect of ruxolitinib. This combination will be further investigated in a phase Ib/II clinical trial in MF.This study was supported by the Subdireccion General de Investigacion Sanitaria (Instituto de Salud Carlos III, Spain) grants PI13/02387 and PI16/01530, and the CRIS against Cancer foundation grant 2014/0120. M.L. holds a postdoctoral fellowship of the Spanish Ministry of Economy and Competitiveness (FPDI-2013-16409).S

Further progress in the study of epsilon iron oxide in archaeological baked clays

[EN] The occurrence of ε-FeO in archaeological samples that have been subjected to high temperatures is gradually being detected by the use of micrometric structural characterization techniques. This work provides new information by revealing that the ε-FeO is formed as a response to temperature, the aggregation state and the position within the baked clay with respect to the nearest heat source. In addition, depending mainly on the atmospheric environment, the temperature reached by the combustion structure, the distance from the heating source and the particle aggregation, other iron oxide magnetic phases are produced. In the baked clay studied here, hematite is found over the whole range of samples studied but its magnetic contribution is negligible. Magnetite is observed at the sample surface, probably due to local atmospheric environment closest to the combustion source. Maghemite is found at all depths up to 6 cm below the sample surface. ε-FeO has a limited distribution, found within 2–3 cm of the sample surface. Furthermore, the viability of this compound as a palaeofield marker has been evaluated in both archaeological and synthetic samples. The results indicate that ε-FeO is able to register the direction of the magnetic field. Linear palaeointensity plots have been obtained in synthetic samples, although the value of the palaeofield could be, sometimes, overestimated.The authors also acknowledge the financial support from the Spanish Ministry of Science, Innovation and Universities under the projects RTI2018-095856-B-C21, CGL2017-87015-P, CGL2017-92285-EXP, CGL2017-92285-EXP/BTE, MAT2017-86540-C4-1-R, MAT2017-87072-C4-2-P and RTI2018-095303-A-C52, from Comunidad de Madrid NANOFRONTMAG S2013/MIT-2850 and NANOMAGCOST S2018/NMT-4321, and from the European Commission under H2020 frame by AMPHIBIAN Project ID: 720853. APO thanks the Ministry of Economy, Industry and Competitiveness (PTA Contract).Peer reviewe

Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia

Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed

Identifying non-destructive growth and maturity indexes of Prickly pear (Opuntia albicarpa S. Var. Burrona) and evaluation of freeze-drying conditions

Around the world, prickly pear fruits are valued as a source of dietary functional compounds and ingredients for innovative foods. Growth and physicochemical changes of Opuntia albicarpa S. fruits were recorded from 0 to 132 days-after-flowering (DAF) to identify non-destructive maturity-indices. Optimum-ripened fruits were freeze-dried to study physicochemical and functional characteristics of dried and rehydrated pulp. Principal component analysis confirmed growth turned into fruit ripening in DAF 99, and it lasted until DAF 132. Changes in color parameters of the peel correlated with fruit texture and pulp sugar content and taste index (P < 0.01). During freeze-drying, plate temperature had more significant effects than the thickness (P < 0.05). At 30°C, color ΔE between dried and fresh slices augmented, but, texture Δ´s (medium force) between rehydrated and fresh pulp was lower. Color tests could be used to harvest commercially-ripened fruits. Freeze-drying at 30°C improves the rehydrated slices texture regarding thickness maintaining rehydration coefficients.Las tunas son apreciadas en todo el mundo como fuente de compuestos funcionales dietarios e ingredientes para alimentos innovadores. Para identificar índices de maduración no destructivos, se registraron cambios en el crecimiento y en los parámetros fisicoquímicos de frutos de Opuntia albicarpa S. entre los días después de la floración (DAF) 0 al 132. Frutos con maduración óptima fueron liofilizados para evaluar características fisicoquímicas y funcionales de pulpa seca y rehidratada. El análisis de componentes principales confirmo que el crecimiento dio lugar a la maduración en el DAF 99 y ésta prosiguió hasta el DAF 132. Los cambios en parámetros de color en cáscara correlacionaron con la textura del fruto, y en pulpa, con el contenido de azúcares y el índice de sabor (P< 0.01). Durante la liofilización, la temperatura de placa tiene más efectos significativos que el espesor (P≤ 0.05). A 30°C, el ΔE de color entre la pulpa seca y fresca aumentó, pero, el Δ de textura (fuerza media) fue menor entre la rehidratada y la fresca. Se pueden emplear evaluaciones de color para cosechar frutos en su madurez comercial, y liofilizar estos frutos a 30°C mejora la textura sin importar el espesor, manteniendo los coeficientes de rehidratación.This work was supported by the SIMORELOS program of CONACyT