506 resultados para POTENTIATED STARTLE
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Dissertação apresentada para a obtenção do grau de mestre na especialidade de Educação Social e Intervenção Comunitária
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Relatório EPE - Relatório de estágio em Educação Pré-Escolar: O presente relatório de estágio de qualificação profissional surge no âmbito da unidade curricular de Prática Pedagógica Supervisionada na Educação Pré- Escolar, por forma a evidenciar o desenvolvimento pessoal e profissional da mestranda ao longo da prática pedagógica. Neste sentido, a mestranda foi desenvolvendo um conjunto de competências, tendo em vista a construção dos seus saberes profissionais, atendendo a uma postura de pendor reflexiva e indagadora, capaz de tomar decisões adequadas de acordo com o contexto educativo onde está inserida, uma vez que o mesmo se carateriza por ser imprevisível. O desenvolvimento dos saberes profissionais foi possibilitado através da adoção da metodologia de investigação-ação, sendo que a mesma se processa numa espiral cíclica de observação, planificação, ação e reflexão, pelo que a reflexão é intrínseca e implícita em todas as fases. Efetivamente, foram várias as estratégias que fomentaram o desenvolvimento desta metodologia, nomeadamente: elaboração de planificações, realização de narrativas colaborativas, elaboração do diário de formação, construção dos guiões de préobservação, reestruturação do Projeto Curricular de Grupo e as reuniões realizadas com o supervisor institucional. Importa, ainda, referir que o desenvolvimento da prática pedagógica em díade de formação, potenciou momentos de reflexão partilhada que contribuíram para a transformação das práticas. A elaboração deste relatório assumiu um papel fulcral, uma vez que despoletou na mestranda uma reflexão crítica sobre as práticas, confluindo na identificação da evolução das suas competências pessoais e profissionais, bem como das dificuldades que ainda predominam, por forma a contorná-las futuramente.
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Lasiodiplodan is an exocellular β-glucan with biological functionalities such as antioxidant, antiproliferative, hypocholesterolemic, protective activity against DNA damage induced by doxorubicin and hypoglycemic activity. Chemical derivatization of polysaccharide macromolecules has been considered as a potentiating mechanism for bioactivity. In this context, this work proposes the derivatization of lasiodiplodan by acetylation. Acetic anhydride was used as derivatizing agent and pyridine as catalyst and reaction medium. The derivatives obtained were evaluated by its water solubility, degree of substitution (DS), antioxidant potential, and characterized by infrared spectroscopy (FT-IR), thermal analysis, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. Acetylated derivatives with different degrees of substitution (1.26; 1.03; 0.66 and 0.48) were obtained, and there was correlation between the concentration of derivatizing agent and DS. FT-IR spectroscopy analysis confirmed the insertion of acetyl groups into derivatized macromolecules (LAS-AC) through of specific bands concerning to carbonyl group (C = O) and increase in C-O vibration. SEM analysis indicated that native lasiodiplodan presents morphological structure in the form of thin films with translucent appearance and folds along its length. Derivatization led to morphological changes in the polymer, including aspects thickness, translucency and agglomeration. Thermal analysis indicated the native sample and derivative with DS 0.48 presented three weight loss stages. The first stage occurred until 125 ° C (loss of water) and there were two consecutive events of weight loss (200 ° C - 400 ° C) attributed to molecule degradation. Samples with DS 1.26; 1.03 and 0.66 demonstrated four weight loss stages. The first stage occurred until 130 ° C (loss of water), following by two consecutive events of weight loss (200 ° C - 392 ° C) attributed to degradation of the biopolymer. The fourth stage was between 381 ° C and 532 ° C (final decomposition) with exothermic peaks between 472 ° C and 491 ° C. X-ray diffraction patterns showed that native and acetylated lasiodiplodan have amorphous structure with semicrystalline regions. Derivatization did not contribute to increased solubility of the macromolecule, but potentiated its antioxidant capacity. Acetylation of lasiodiplodan allowed to obtaining a new macromolecule with higher antioxidant potential than the native molecule and with technological properties applicable in various industrial sectors.
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International audience
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Colorectal cancer (CRC) is the third most common cancer worldwide. Various factors such as age, lifestyle and dietary patterns affect the risk of having CRC. Epidemiological studies showed a chemopreventive effect of soy consumption against CRC. However, which component(s) of soybean is associated with this reduced risk is not yet fully delineated. The objective of this research was to evaluate the anti-colon cancer potential of lunasin isolated from defatted soybean flour using in vitro and in vivo models of CRC. Lunasin was isolated from defatted soybean flour by a combination of different chromatographic and ultrafiltration techniques. The anti-colon cancer potential of lunasin was determined using different human colon cancer cell lines in vitro and a CRC liver metastasis model in vivo. Lunasin caused cytotoxicity to different human colon cancer cells with an IC50 value of 13.0, 21.6, 26.3 and 61.7 µM for KM12L4, RKO, HCT-116 and HT-29 human colon cancer cells, respectively. This cytotoxicity correlated with the expression of the α5 integrin on human colon cancer cells with a correlation coefficient of 0.78. The mechanism involved in the cytotoxic effect of lunasin was through cell cycle arrest and induction of the mitochondrial pathway of apoptosis. In KM12L4 human colon cancer cells, lunasin caused a G2/M phase arrest increasing the percentage of cells at G2/M phase from 12% (PBS-treated) to 24% (treated with 10 µM lunasin). This arrest was attributed to the capability of lunasin to increase the expression of cyclin dependent kinase inhibitors p21 and p27. At 10 µM, lunasin increased the expression of p21 and p27 in KM12L4 colon cancer cells by 2.2- and 2.3-fold, respectively. Flow cytometric analysis showed that lunasin at 10 µM increased the percentage of cells undergoing apoptosis from 13.6% to 24.7%. This is further supported by fluorescence microscopic analysis of KM12L4 cells treated with 10 µM lunasin showing chromatin condensation and DNA fragmentation. The mechanism involved is through modification of proteins involved in the mitochondrial pathway of apoptosis in KM12L4 cells as 10 µM lunasin reduced the expression of the anti-apoptotic Bcl-2 protein by 2-fold and increased the expression of the pro-apoptotic proteins Bax, cytochrome c and nuclear clusterin by 2.2-, 2.1- and 2.3- fold, respectively. This led to increased expression and activity of the executioner of apoptosis, caspase-3 by 1.8- and 2.3-fold, respectively. This pro-apoptotic property of lunasin can be attributed to its capability to internalize into the cytoplasm and nucleus of colon cancer cells 24 h and 72 h after treatment, respectively. In addition, lunasin mediated metastasis of colon cancer cells in vitro by inhibiting the focal adhesion kinase activation thereby reducing expression of extracellular regulated kinase and nuclear factor kappa B and finally inhibiting migration of colon cancer cells. In KM12L4 colon cancer cells, 10 µM lunasin resulted in the reduction of phosphorylation of focal adhesion kinase and extracellular regulated kinase by 2.5-fold, resulting in the reduced nuclear translocation of p50 and p65 NF-κB subunits by 3.8- and 1.4-fold, respectively. In an in vivo model of CRC liver metastasis, daily intraperitoneal administration of lunasin at 4 mg/kg body weight resulted in the inhibition of KM12L4 liver metastasis as shown by the reduction of the number of liver metastases from 28 (PBS-treated) to 14 (lunasin-treated, P = 0.047) and reduction in tumor burden as measured by liver weight/body weight from 0.13 (PBS-treated) to 0.10 (lunasin-treated, P = 0.039). Moreover, lunasin potentiated the anti-metastatic effect of the chemotherapeutic drug oxaliplatin given at 5 mg/kg body weight twice per week. Lunasin and oxaliplatin combination resulted in a more potent inhibition of outgrowth of KM12L4 cell metastases to the liver reducing the number of liver metastases by 6-fold and reducing the tumor burden in the liver by 3-fold when compared to PBS-treated group. This can be attributed by the capability of lunasin and oxaliplatin to reduce expression of proliferating cell nuclear antigen in liver-tumor tissue as measured by immunohistochemical staining. The results of this research for the first time demonstrated the anti-colon cancer potential of lunasin isolated from defatted soybean flour which might contribute to the chemopreventive effect of soybean in CRC as seen in different epidemiological studies. In conclusion, lunasin isolated from defatted soybean flour mediated colon carcinogenesis by inducing apoptosis and preventing outgrowth of metastasis. We suggest that the results of this research serve as a basis for further study on the chemopreventive effect of lunasin against CRC and a possible adjuvant role for lunasin in therapy of patients with metastatic CRC.
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O Relatório de Estágio, elaborado no âmbito do Mestrado em Ensino do 1.º e 2.º Ciclo do Ensino Básico, pretende ser um reflexo da prática educativa realizada e um contributo para a formação pessoal e profissional da mestranda, caracterizando-se por uma atitude crítica, reflexiva e investigativa. A revisitação e a análise refletida da ação, e das opções didático-pedagógicas que a orientaram, permitiram traçar um percurso para a melhoria das práticas educativas, determinante para o desenvolvimento da identidade docente. Desta experiência, salienta-se, por um lado, o trabalho realizado em par pedagógico, em todos os momentos do ciclo da supervisão, que potenciou momentos de debate e de reflexão – e, consequentemente, uma prática informada, criativa e rigorosa, fundamentada em princípios e valores partilhados. Por outro lado, destaca-se também a influência da filosofia do Movimento da Escola Moderna na conceção e implementação da Prática Educativa Supervisionada (PES), o que contribuiu ainda para a valorização da colaboração entre todos os atores envolvidos neste palco que é a ação educativa. Ao longo da PES, o par pedagógico privilegiou situações de ensino e de aprendizagem que favorecessem a cooperação e a comunicação bem como atividades que adequadas às necessidades do contexto educativo e aos interesses das crianças, baseada numa relação horizontal entre professores e alunos. Deste modo, a PES, sustentada num exercício de constante articulação entre teoria e prática, constituiu uma oportunidade de experienciar os desafios da docência e de compreender como é que esta pode concorrer para uma sociedade mais justa, livre e democrática.
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Resumen La desmesurada forma en la que está creciendo la ciudad y la sociedad en general, ha ocasionado un desequilibrio en la relación personas - espacio público recreacional. A partir de esta condición se ha tomado la iniciativa nacional de reciclar espacios semipúblicos y convertirlos en equipamientos que contribuyan a la formación de los ciudadanos. Los urbanistas señalan como fin último el mejorar la calidad de vida, siendo en el espacio urbano lo público el núcleo a partir del cual se contribuye a este objetivo. Los cuarteles militares en muchas de las urbes del país han sido alcanzados por la urbanización, pudiéndose ocupar estos sitios para solucionar la problemática urbana que se ha generado en torno a estos lugares. En esta tesis se evidencia que la arquitectura se piensa y se produce desde el lugar, tomando como referencia la metodología del análisis espacial urbano, y complementándola a su vez con la obra y el pensamiento de Rafael Pina Lupiañez. El sector del predio de la Brigada de Artillería Portete es el espacio idóneo para una intervención, en el cual se ha implantado la propuesta de un parque urbano recreacional, donde no solo se ha potencializado las características trópicas y antrópicas sino también se ha conseguido mitigar las condiciones desfavorables. Se ha considerado este proyecto como el precursor para facilitar el cambio de uso a estos espacios semipúblicos restringidos que tanto se necesitan dentro de la ciudad, siendo un primer acercamiento con el cuerpo militar.
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La ciudad de General Leónidas Plaza, localizada en el Cantón Limón Indanza en la Amazonía del Ecuador, posee una serie de recursos naturales y culturales tangibles e intangibles que deben ser resguardados y potencializados. Esta ciudad, es un asentamiento con pocos años de fundación por lo que se encuentra en constante desarrollo económico y social. Estos cambios y transformaciones demandan espacios que permitan la interacción social de la población a través de la generación de zonas de esparcimiento y recreación. Los espacios de recreación en la cabecera cantonal, presentan deficientes condiciones en cuanto a su funcionamiento e infraestructura, causando la degradación de la imagen urbana, limitando el correcto desenvolvimiento de las actividades recreacionales y causando la pérdida de espacios públicos que permitan una integración socio cultural de la población. En la actualidad, se ha destinado un espacio a los márgenes del río Yunganza para la proyección de El Parque de la Juventud. La recuperación de este espacio como un lugar de esparcimiento, es necesaria para generar un proyecto que integre el contexto natural y edificado de la ciudad, con el fin de promover las actividades recreativas y evitar la degradación del paisaje y su imagen urbana.
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Medical research has greatly beneited from molecular biology and increasingly relies on tools from the “omics” disciplines (mainly genomics, transcriptomics, proteomics and metabolomics). The availability of biological samples preserved with high quality standards is a sine qua non condition for such studies and their repositories are referred to as biobanks. Biobanks support the transportation, storage, preservation, and initial pathological and analytical examinations of biospecimens, as well as the protection of relevant information and the comparison of clinical and laboratory findings. A biobank facility is one of the most valuable tools the academic medicine organizations can offer to their researchers to improve the competitiveness of their current and future medical research. it acts as an essential bridge and an effective catalyst for research synergies between basic and clinical sciences, and it can be potentiated with efforts to raise funds for acquiring and maintaining cutting-edge analytical infrastructure to better serve its clinical, pharmaceutical and biotech clients.
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Contexto: La eficacia de los cannabinoides en el dolor neuropático es desconocida. El control del dolor es determinante en los pacientes ya que genera un impacto negativo en la calidad de vida de los pacientes. Objetivo: El presente trabajo pretende demostrar la evidencia sobre la eficacia de los medicamentos cannabinoides en el control del dolor neuropático oncológico, mediante la evaluación de la literatura disponible. Metodología: Se realizó una revisión sistemática de literatura incluyendo estudios experimentales, observacionales y revisiones sistemáticas en un periodo de 15 años. Se incluyeron todos los estudios desde el años 2000 con evidencia IB según la escala de evidencia de Oxford. Resultados: Cuatro estudios cumplieron criterios para su inclusión, sin embargo la evidencia es baja y no permite recomendar o descartar los cannabinoides como terapia coadyuvante en control del dolor neuropático oncológico. La combinación de THC/CDB (Sativex®) parece ser un medicamento seguro pues no se reportaron muertes asociadas a su uso, sin embargo la presentación de eventos adversos a nivel gastrointestinal y neurológico podría aumentar el riesgo de interacciones medicamentosas y tener un impacto negativo en la calidad de vida de los pacientes oncológicos. Conclusiones: No hay suficiente literatura y la evidencia no es suficiente para recomendar o descartar el uso de los cannabinoides en dolor neuropático oncológico. Futuros estudios deben realizarse para analizar el beneficio de estos medicamentos. Aunque ética y socialmente hay resistencia para el uso de los cannabinoides, actualmente hay una gran discusión política en el mundo y en Colombia para su aceptación como terapia en el control del dolor.
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Acute myeloid leukemia (AML) is a haematological malignancies arising from the accumulation of undifferentiated myeloid progenitors with an uncontrolled proliferation. The genomic landscape of AML revealed that the disease is characterized by high level of heterogeneity and is subjected to clonal evolution driven by selective pressure of chemotherapy. In this study, we investigated the therapeutic effects of the inhibition of BRD4 and CDC20 in vitro and ex vivo. We demonstrated that inhibition of BRD4 with GSK1215101A in AML cell lines was effective under hypoxia. It induced the activation of antioxidant response both, at transcriptomic and metabolomic levels, driven by enrichment of NRF2 pathway under normoxic and hypoxic condition. Moreover, the combined treatment with Omaveloxolone, a drug inducing NRF2 activation and NF-κB inhibition, potentiated the effects on apoptosis and colony forming capacity of stem progenitor cells. Lastly, gene expression profiling data revealed that combination treatment induced major changes in genes related to cell cycle, together with enrichment of cell differentiation pathways and negative regulation of WNT, in normoxia and hypoxia. Regarding CDC20, we observed its up-regulation in AML patients. Treatment with two different inhibitors, Apcin and proTAME, was effective in primary AML cells and in AML cell lines, through induction of apoptosis and mitotic arrest. The lack of correlation between proliferation markers and CDC20 levels in AML cell subpopulations supports the idea of alternative CDC20 functions, independent from its essential role during mitosis. CDC20-KD experiments conducted in AML cell lines revealed a mild effect on apoptosis induction, but no significant change in cell cycle progression. In summary, these results allowed the identification of a new strategy combination to improve the effects of BRD4 inhibition on LSC residing in the BM hypoxic niche, and provide some new evidence regarding the potential role of CDC20 as a new target for AML treatment.