Sistemas microfisiológicos compostos por organoides humanos em dispositivos microfluídicos: avanços e desafios

Introduction: Models with higher predictive capacity and able to produce results at lower costs and in shorter times are needed for drug development. The microphysiological systems (MPS) that cultivate human tissues in three-dimensional histoarchitecture (3D) are promising alternatives for these objectives. Objective: This review work aims to address the state of the art of SMF development and illustrate the initial Brazilian experience with this technology. Method: The research and data collection covering the theme “Microphysiological Systems”, and the subtopics “Microfluidic Devices” and “3D Culture of Human Cells”, was based on electronic search in Capes Journals Portal, scientific databases Scopus, PubMed and Science Direct and with the Google Scholar search tool. Results: Among the existing microphysiological systems, those that are characterized by the culture of human tissues organized in three - dimensional histoarchitecture in microfluidic devices were recently introduced, as being the most promising ones. In addition, between the years 2000-2017, we recorded approximately increases of 12, 985 and 380 times in the number of academic publications related to the areas of Microfluidics, Organ-on-a-Chip and MPS respectively, illustrating the impact of this technology today. Conclusions: This relatively recent technology has high potential to overcome the limitations of current in vitro experimental models.Introdução: Modelos com maior capacidade preditiva e que produzam resultados a custos mais baixos e em prazos menores são necessários para o desenvolvimento de fármacos. Os sistemas microfisiológicos (SMF) que cultivam tecidos humanos em histoarquitetura tridimensional (3D) apresentam-se como alternativas promissoras para esses objetivos. Objetivo: Este trabalho de revisão tem por objetivo abordar o estado da arte mundial do desenvolvimento dos SMF e ilustrar a experiência brasileira inicial com essa tecnologia. Métodos: A pesquisa e coleta de dados abrangendo a temática “Sistemas Microfisiológicos”, e os subtemas “Dispositivos Microfluídicos” e “Cultura 3D de Células Humanas”, foi baseada em busca eletrônica no Portal de Periódicos Capes, nas bases de dados científicas Scopus, PubMed e Science Direct e utilizando a ferramenta de busca Google Scholar. Resultados: Dentre os sistemas microfisiológicos existentes, os que são caracterizados pelo cultivo de tecidos humanos organizados em histoarquitetura tridimensional em dispositivos microfluídicos foram recentemente introduzidos, como sendo os mais promissores. Além disso, entre os anos 2000–2017, registramos aumentos de aproximadamente 12, 985 e 380 vezes no número de publicações acadêmicas relacionadas às áreas de Microfluídica, Organ-on-a-Chip e SMF respectivamente, ilustrando o impacto dessa tecnologia atualmente. Conclusões: Essa tecnologia relativamente recente tem alto potencial para superar as limitações dos modelos experimentais in vitro atuais

CONCERTO AL PIANO. SUSTAINABLE URBAN TRANSFORMATIONS

Concerto AL Piano, in Alessandria at the NW of Italy, is one of the 58 integrated energy demonstration sites promoted by the European Commission within the 6th and 7th Framework Programme. Concerto AL Piano is aimed at demonstrating the economic and social benefits in investing in energy saving and renewable energy in urban regeneration. The project includes a mix of interventions: the renovation of existing social housing, the construction of new eco-buildings and the provision of a cogeneration district heating, integrated in the urban environment

Intitulados: una mirada desde la comunicación visual

Cuando observamos documentos cuyos encabezados presentan lo que en archivística se conoce como intitulados, difícilmente podemos escapar al análisis de su forma, su composición general, o de los múltiples elementos que los constituyen, como la tipografía, los íconos y los diferentes recursos gráficos. Más allá de la faz estética o decorativa, que por supuesto poseen -y por cierto es plausible de otro tipo de análisis-, estos mensajes presentan una intención manifiesta de comunicación, una propuesta superadora a la función primaria del documento, un plus o valor agregado sobre piezas que tienen funciones específicas, tales como la comercial o administrativa. Así, de esta forma, materiales diversos de papelería comercial, adquieren una nueva dimensión vinculada a la entidad emisora. Desarrollaremos una mirada sobre estos complejos sistemas de signos desde la perspectiva del esquema básico de comunicación propuesto en la Teoría de la Información del lingüista Roman Jakobson: el emisor, los factores propios del mensaje, y el receptor. El propósito es realizar una lectura que nos permita entender de qué forma se generaron estas composiciones, y cómo llegaron -y llegan aún hoy por supuesto- a percibirse.Facultad de Bellas Arte

The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life in Drosophila

Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. However, the mutations’ effects throughout adult life are unclear. In this study, we identify that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW), controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. We found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. By expressing csw-RNAi in different organs, we determined that CSW extended life span by acting in organs that regulate energy availability, including gut, fat body and neurons. In contrast to that in control animals, loss of CSW leads to reduced homeostasis in metabolic rate during activity. Clinically relevant gain-of-function csw allele reduced life span, when expressed in fat body, but not in other tissues. However, overexpression of a wild-type allele did not affect life span, showing a specific effect of the gain-of-function allele independently of a gene dosage effect. We concluded that CSW normally regulates life span and that mutations in SHP2 are expected to have critical effects throughout life by insulin-dependent mechanisms in addition to the well-known RAS-ERK1/2-dependent developmental alterations.Fil: Ruzzi, Leonardo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Schilman, Pablo Ernesto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; ArgentinaFil: Gelb, Bruce D.. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Finite element analysis and fracture resistance testing of a new intraradicular post

OBJECTIVES: The objective of the present study was to evaluate a prefabricated intraradicular threaded pure titanium post, designed and developed at the São José dos Campos School of Dentistry - UNESP, Brazil. This new post was designed to minimize stresses observed with prefabricated post systems and to improve cost-benefits. MATERIAL AND METHODS: Fracture resistance testing of the post/core/root complex, fracture analysis by microscopy and stress analysis by the finite element method were used for post evaluation. The following four prefabricated metal post systems were analyzed: group 1, experimental post; group 2, modification of the experimental post; group 3, Flexi Post, and group 4, Para Post. For the analysis of fracture resistance, 40 bovine teeth were randomly assigned to the four groups (n=10) and used for the fabrication of test specimens simulating the situation in the mouth. The test specimens were subjected to compressive strength testing until fracture in an EMIC universal testing machine. After fracture of the test specimens, their roots were sectioned and analyzed by microscopy. For the finite element method, specimens of the fracture resistance test were simulated by computer modeling to determine the stress distribution pattern in the post systems studied. RESULTS: The fracture test presented the following averages and standard deviation: G1 (45.63±8.77), G2 (49.98±7.08), G3 (43.84±5.52), G4 (47.61±7.23). Stress was homogenously distributed along the body of the intraradicular post in group 1, whereas high stress concentrations in certain regions were observed in the other groups. These stress concentrations in the body of the post induced the same stress concentration in root dentin. CONCLUSIONS: The experimental post (original and modified versions) presented similar fracture resistance and better results in the stress analysis when compared with the commercial post systems tested (08/2008-PA/CEP)

China-EU Energy Cooperation Roadmap 2020 _ Concept Note

The process for the definition of an Energy Cooperation Roadmap between the EU and China was officially initiated at the first meeting of the Energy Security Working Group held in Beijing in February 2013, following the China-EU Joint Declaration on Energy Security of May 2012 that stated the formal establishment of the relationships between China and the EU as energy consumers and strategic partners. This Concept Note on China-EU Energy Cooperation Roadmap 2020 has been elaborated by the Europe-China Clean Energy Centre (EC2) and it provides suggestions on cooperation goals and recommendations for a Roadmap to 2020

Arbuscular mycorrhizal fungi populations in relationship with soil properties and host plant in grasslands of Tierra del Fuego

El sobrepastoreo ovino en pastizales de suelos ácidos de Tierra del Fuego ha determinado una disminución de la cobertura de gramíneas de interés forrajero y un aumento de la cobertura de un arbusto postrado poco apetecible (murtilla, Empetrum rubrum). Se seleccionaron suelos sometidos a distinta modalidad de pastoreo que tenían características y vegetación particulares. Se midió la cantidad total y la diversidad de esporas de hongos micorrízicos arbusculares en los cuatro suelos y en la rizósfera de tres de las gramíneas más frecuentes (Festuca gracillima, Deschampsia flexuosa y Poa rigidifolia) en los pastizales de la estepa fueguina. En el suelo rizosférico se determinó la cantidad y la diversidad de esporas de hongos micorrízicos arbusculares, y en las plantas el contenido de P, N y el porcentaje y morfología de la colonización micorrízica en raíces. Se identificaron las esporas de las tres especies de hongos micorrízicos arbusculares más abundantes. Glomus fasciculatum fue la especie de mayor frecuencia. La cantidad total de esporas y la colonización en raíz dependieron del suelo, de la especie hospedante y de la interacción entre ambas variables. Poa rigidifolia presentó el mayor número total de esporas en su rizósfera y la mayor colonización en raíz. Para todos los suelos y plantas estudiadas no hubo relación entre la cantidad total de esporas y el porcentaje colonizado de la raíz, ni tampoco entre este porcentaje y las concentraciones de N y P en planta. La cantidad total de esporas se correlacionó positivamente con las medidas de N, P, Ca, K y pH del suelo. Sin embargo, al analizar el suelo y las planta de manera separada, tanto la existencia de relación entre la cantidad de esporas y el porcentaje colonizado como la dirección y el sentido de la misma dependieron de la combinación suelohospedante.Sheep overgrazing in grasslands of Tierra del Fuego has determined a decrease of grass cover but an increase in a prostrate shrub of low forage value (murtilla, Empetrum rubrum). We selected soils with different modality of grazing, which determined particular characteristics in soil and vegetation. Abundance and diversity of spores of arbuscular mycorrhizal fungi were studied on the four soils and on three of the most frequent grasses (Festuca gracillima, Deschampsia flexuosa y Poa rigidifolia). Spore counts were measured in rizospheric soil, along with nutrient content (P and N) in plants, and percentage of root length colonised and the morphology of colonisation. The most frequent species was Glomus fasciculatum. The soil, the host plant, and the interaction between both variables influenced total spore counts and percentage of root length colonised. Poa rigidifolia showed the highest number of rizospheric spores and the highest percentage of root length colonised. Neither relationship between spore counts and root colonisation nor relationship between root colonisation and P or N plant contents were observed using the whole data (soils and plants). Total spore counts were correlated positively with measures of N, P, Ca, K and pH in soil. Nevertheless, when soils and plants were studied separately, both the relationship between spore counts and percent of root colonised and its direction depended on the soil-host combination

Estudo comparativo entre tratamento convencional e tratamento com heparina tópica para a analgesia de queimaduras

OBJETIVOS: Este estudo prospectivo, randomizado, aberto e controlado por comparador ativo teve o objetivo de avaliar a eficácia analgésica e tolerabilidade da heparina não-fracionada administrada topicamente no tratamento de queimaduras. MÉTODOS: Cinquenta e oito pacientes do sexo masculino ou feminino foram randomizados para tratamento convencional (C) ou tratamento com heparina tópica (HT). Foram incluídos pacientes com: idade entre 18 e 55 anos, queimaduras de 2º e 3º graus por fogo ou escaldo em 10% a 30% da superfície corpórea (SC), sem história de diáteses hemorrágicas ou hipersensibilidade à heparina e com área queimada em 3º grau menor de 10% da SC. O grupo C realizou periodicamente balneoterapia terapêutica para desbridamento das lesões seguida de curativos com sulfadiazina de prata. O grupo HT realizou o primeiro desbridamento e teve suas áreas queimadas deixadas expostas para receber três vezes ao dia heparina não fracionada em spray na dose de 4200 UI para cada 1% de SC queimada. A eficácia analgésica foi avaliada nos 38 pacientes que completaram o estudo pela demanda de medicamentos analgésicos e pela Escala Analógico Visual de Dor (EAV). A tolerabilidade foi avaliada nos 58 pacientes randomizados pela incidência comparativa de reações adversas nos dois grupos. RESULTADOS: O grupo HT solicitou menos analgésicos (11,83 ± 9,38 por paciente no grupo HT contra 33,35 ± 20,63 no grupo C, pOBJECTIVE: This was a prospective, randomized, open-label study controlled by active comparator. The aim was to assess analgesic efficacy and overall tolerability of a burn treatment based on topic administration of unfractionated heparin. METHODS: Fifty eight male or female patients were randomized for conventional treatment (group C) or topical heparin treatment (group TH). Ages of patients enrolled ranged from 18 to 55 years. They had 2nd and 3rd degree burns on 10% to 30% of the body surface (BS) caused by fire or scald, no hemorrhagic diseases, no hypersensitivity to heparin and less than 10% of the BS burned to 3rd degree. The group C had frequent debridement under anesthesia or analgesia and received silver sulfadiazine dressings. The group TH had the first debridement and their wounds left open to receive 4200 IU of unfractionated heparin topically for each 1% of burned BS, three times daily. Efficacy was evaluated from files of the 38 patients who completed the study according to demand of analgesic medications and response to the pain Visual Analog Scale (VAS). Tolerability was evaluated from the files of all 58 randomized patients by the comparative incidence of adverse reactions. RESULTS: The group TH demanded less analgesic medications (11.83 ± 9.38 per patient against 33.35 ± 20.63 for the C group, p<0.01), reported less pain in the VAS, had less fever and more bleeding than group C. There was no difference in the incidence of local infection, septicemia and safety exams. CONCLUSION: The group TH presented less pain without important tolerability problems

Molecular analysis of holoprosencephaly in South America

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.250262Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq