Learning From Animal Models of Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) affects 2%-3% of the population worldwide and can cause significant distress and disability. Substantial challenges remain in the field of OCD research and therapeutics. Approved interventions alleviate symptoms only partially, with 30%-40% of patients being resistant to treatment. Although the etiology of OCD is still unknown, research evidence points toward the involvement of cortico-striato-thalamocortical circuitry. This review focuses on the most recent behavioral, genetics, and neurophysiologic findings from animal models of OCD. Based on evidence from these models and parallels with human studies, we discuss the circuit hyperactivity hypothesis for OCD, a potential circuitry dysfunction of action termination, and the involvement of candidate genes. Adding a more biologically valid framework to OCD will help researchers define and test new hypotheses and facilitate the development of targeted therapies based on disease-specific mechanisms

Pré-escolar: emoções em contexto de aprendizagem multicultural

Este artículo tiene como objetivo presentar el estudio sobre el desarrollo de varias habilidades y orientaciones curriculares en la educación de la primera infancia en el contexto portugués y alemán. El estudio se centra en Alemania, en la región de Baviera, en Múnich. Parte de la investigación de maestría en el área de la supervisión pedagógica. El estudio pone de relieve la importancia de desarrollaruna nueva "tendencia": la competencia emocional en Preescolar. Así que demuestra la importancia de las emociones en las actividades educativas relacionadas con el desarrollo de otras habilidades, especialmente las cognitivas y sociales. La metodología utilizada para el estudio fue una triangulación de instrumentos compuesta por la observación en una institución de Educación Infantil de carácter intercultural en Munich; el estudio de los documentos curriculares de Preescolar de Baviera y la aplicación de una encuesta a pedagogos de la institución. El presente estudio pretende analizar el conocimiento de las emociones sobre el aprendizaje en un contexto intercultural en ábito de preescolar.O presente artigo pretende apresentar o estudo em desenvolvimento sobre o tema competências transversais e orientações curriculares na educação infantil, no contexto português e alemão. Privilegiando-se o estudo realizado na Alemanha, região da Baviera em Munique parte de uma investigação de mestrado na área da supervisão pedagógica. O estudo realizado destaca a importância do desenvolvimento de um novo “trend”: a competência emocional no Pré-Escolar. Comprovando assim a relevância das emoções nas atividades pedagógicas inerentes para desenvolvimento de outras competências, especialmente nas cognitivas e sociais. A metodologia utilizada para o estudo foi a triangulação de instrumentos composta pela observação numa instituição de Educação Infantil em Munique de caráter intercultural; o estudo dos documentos curriculares Pré-escolar da Baviera e a aplicação de um inquérito às pedagogas da instituição. O presente estudo perspetiva analisar o conhecimento acerca das emoções e sobre a aprendizagem em contexto intercultural no âmbito do préescolar

Crops Diversification and the Role of Orphan Legumes to Improve the Sub-Saharan Africa Farming Systems

Agriculture is the main economic revenue in sub-Saharan African countries, playing a key role on smallholder livelihoods as household incomes and as food. Food insecurity is known to increase with the inevitable climate changes, which already affect the major farming systems, sub-Saharan Africa (SSA) being particularly susceptible, mostly due to the high dependence of rainfall for crop cycles. As such, to promote food security in a long run, new farming systems have to become more sustainable and productive at the same time. In this chapter, a global overview of major farming systems in sub-Saharan Africa is provided, and current and future production scenarios are discussed. Moreover, some of the major pillars under the sustainable land use intensification are highlighted, and the potential of the undervalued African legumes toward a sustainable crop production is debated. Finally, an outline of key opportunities to diversify cropping systems is explored along with the benefits associated to integration of local and “orphan legumes” that are considered. It is argued that the use of these “orphan legumes” and the implementation of appropriated management approaches will promote a sustainable production of more food from the same land area, relying on mutually beneficial ecological relationships and reducing environmental impacts

Transgenic labeling of parvalbumin-expressing neurons with tdTomato

Parvalbumin (PVALB)-expressing fast-spiking interneurons subserve important roles in many brain regions by modulating circuit function and dysfunction of these neurons is strongly implicated in neuropsychiatric disorders including schizophrenia and autism. To facilitate the study of PVALB neuron function we need to be able to identify PVALB neurons in vivo. We have generated a bacterial artificial chromosome (BAC) transgenic mouse line expressing the red fluorophore tdTomato under the control of endogenous regulatory elements of the Pvalb gene locus (JAX # 027395). We show that the tdTomato transgene is faithfully expressed relative to endogenous PVALB expression throughout the brain. Furthermore, targeted patch clamp recordings confirm that the labeled populations in neocortex, striatum, and hippocampus are fast-spiking interneurons based on intrinsic properties. This new transgenic mouse line provides a useful tool to study PVALB neuron function in the normal brain as well as in mouse models of psychiatric disease.National Institute of Mental Health (U.S.) (Grant 5R01MH097104

Investigations of bioresponsive polymers in triple negative breast cancers

Triple negative breast cancer (TNBC) is a subtype of breast cancer which is defined by the lack of expression of standard molecular targets: estrogen and progesterone receptors and the lack of expression or amplification of human epidermal growth factor receptor 2. TNBC is characterised by aggressive progression, lack of standard therapies and poorer overall survival rates for patients. Existing targeted therapies are not applicable to this type of breast cancer; thus, conventional chemotherapy still remains the standard of care for the treatment of TNBC. The present work aims to develop functionalised biodegradable nanocarriers for the treatment of triple negative breast cancer using a novel triblock copolymer. Different strategies are used for the development of nanocarriers by taking advantage of endogenous specific stimulus or receptor expression in the triple negative breast cancer cells. In chapter 2, docetaxel (DTX)-loaded redox responsive crosslinked micelles are prepared using a novel biocompatible and biodegradable functionalised triblock copolymer mPEG-b-poly(D,L-lactide-co-α-N3-ε-caprolactone) for the treatment of TNBC. The empty micelles do not show any cytotoxicity in vitro in three cell lines tested i.e. MDA-MB-231 (triple-negative breast cancer), MCF7 (breast cancer) and MCF10A (breast epithelial cell line), whereas DTX-loaded reducible crosslinked micelles exhibit higher cytotoxicity against TNBC cells. Crosslinked and non-crosslinked micelles show high cellular uptake in MDA-MB-231 TNBC cells which is found to be concentration-dependent. The DTX-loaded crosslinked micelles induce higher levels of apoptosis, as assessed by the annexin V/PI assay and increase the caspase 3/7 activity in MDA-MB-231 cells in comparison to the cells treated with DTX-loaded un-crosslinked micelles and free DTX. Biodistribution results in healthy mice show that crosslinked micelles have increased stability in vivo in comparison to their non-crosslinked counterpart. Moreover, both formulations are found to be well tolerated and do not promote any adverse effect in vivo. In chapter 3, a triple negative breast cancer 3D cell culture model is developed for assessing the efficacy of docetaxel (DTX)-loaded crosslinked micelles against TNBC three-dimensional (3D) multicellular tumour spheroids. In addition, the ability of the redox responsive DTX-loaded crosslinked micelles to overcome the DTX resistance of the TNBC tumour spheroids is also investigated. The results of the efficacy assays show that DTX-loaded crosslinked micelles have the best efficacy against TNBC spheroids compared to control (un-crosslinked micelles) and free DTX. Moreover, the results indicate that 3D tumour spheroids exhibited higher innate resistance, especially to free docetaxel. In chapter 4, EGFR-targeted polymeric micelles using a peptide (GE11) that binds specifically to EGF receptor are prepared for synergistic co-delivery of docetaxel (DTX) and doxorubicin (DOX) aiming to treat triple negative breast cancer tumours. Results show that GE11-linked micelles at different peptide densities do not promote any toxicity in normal epithelial and breast cancer cell lines. However, the 15% GE11-linked micelles have a higher uptake in 2D monolayer and 3D spheroids of TNBC when compared to the 25% GE11-linked micelles and untargeted micelles. In addition, an advanced 3D co-culture system model of triple negative breast cancer with a non-tumorigenic cell line is also developed for the future assessment of the safety and efficacy of the formulations. Taken together, the results demonstrate that the designed functionalised micelles can be a promising and effective carrier system for future clinical applications to TNBC

Hybrid multisite silicon neural probe with integrated flexible connector for interchangeable packaging

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).This work has been funded by: national funds through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020 and UIDP/50026/2020; the projects NORTE-01-0145- FEDER-000013 (“PersonalizedNOS—New avenues for the development of personalized medical interventions for neurological, oncologic and surgical disorders”) and NORTE-01-0145-FEDER-000023 (“FROnTHERA—Frontiers of technology for theranostics of cancer, metabolic and neurodegenerative diseases”), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI— Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122); FCT project PTDC/MEDNEU/ 28073/2017 (POCI-01-0145-FEDER-028073); and The Branco Weiss fellowship—Society in Science, (ETH Zurich)

Saccharomyces cerevisiae and Dekkera bruxellensis interactions in alcoholic fermentations: growth and 4-ethylphenol production

The yeast Dekkera/Brettanomyces bruxellensis can cause enormous economic losses both in wine industry and fuel-ethanol processes due to production of phenolic off-flavour compounds and low ethanol productivities. In winemaking this microbial hazard is usually tackled by the use of chemical preservatives such as sulphur dioxide. In spite of this, D. bruxellensis strains are frequently found in wines at low levels (ca 103 cells/ml) where they can metabolise residual sugars producing phenolic off-flavours compounds, such as 4-ethyl phenol. In the present work we investigated S. cerevisiae and D. bruxellensis interactions during alcoholic fermentations and evaluated the effectiveness of antimicrobial peptides secreted by S. cerevisiae to prevent growth of the main wine spoilage yeast and the production of 4-ethylphenol. Several fermentations were performed with single cultures of D. bruxellensis and mixed cultures of S. cerevisiae and D. bruxellensis, both in synthetic grape juice (SGJ) and grape must. Yeast growth (culturability and viability) and fermentation performance (i.e. sugars consumption, ethanol and 4-ethylphenol production) of those fermentations was accessed by different methods, namely by florescence in situ hybridization and flow cytometry. Results showed that S. cerevisiae significantly reduced the growth of D. bruxellensis and the production of 4-ethylphenol both in SGJ and grape must fermentations performed with mixed cultures. Moreover, our work also showed that antimicrobial peptides secreted by S. cerevisiae are effective to prevent growth of D. bruxellensis and production of phenolic off-flavor compounds in wine

A unidade afetivo-cognitiva : aspectos metodológicos e conceituais a partir da psicologia histórico-cultural

Orientador : Prof. Dr. João Henrique RosslerDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Humanas, Programa de Pós-Graduação em Psicologia. Defesa: Curitiba, 10/11/2015Inclui referências : f. 187-192Resumo: O presente estudo, de caráter teórico-metodológico, teve por objetivo sistematizar o conceito de unidade afetivo-cognitiva a partir da Psicologia Histórico-Cultural. Esse objetivo se justifica pela escassez de estudos acerca deste tema na Psicologia e pela observância de que há uma predominância de visões dualistas acerca da razão e da emoção nos estudos psicológicos. Nesse sentido, o estudo da unidade afetivo-cognitiva pode trazer acréscimos à Psicologia por discutir os aspectos metodológicos da cisão razão/emoção e por evidenciar, mais detalhadamente, a união entre esses processos como parte essencial do processo humano de apreensão e conhecimento da realidade. Sendo assim, buscou-se situar metodologicamente o materialismo histórico-dialético e a Psicologia Histórico-Cultural como descendente desse método para, a partir dessa base teórica, discutir a constituição da consciência humana e da estrutura da atividade como unidades de análise da unidade afetivo-cognitiva, bem como compreender a condição humana alienada na sociedade de classes capitalista. Com isso, analisou-se, a partir de Leontiev e Vigotski, a estrutura da atividade humana e sua expressão pelos significados sociais e sentidos pessoais como unidade afetivo-cognitiva, chegando-se, por fim, à expressividade dessa unidade afetivo-cognitiva na constituição da personalidade humana. Essa investigação resultou na constatação de que a estrutura da atividade e a constituição da consciência humana demandam funções afetivo-cognitivas para formar a imagem subjetiva da realidade objetiva no psiquismo humano. Por isso, indicou-se, conforme afirma Vigotski, que entender a unidade afetivo-cognitiva como sistema semântico da consciência, demanda o destrinchamento da relação entre a atividade humana e a forma como o ser torna essa atividade consciente. Foi esse o esforço principal empregado nesse trabalho, isto é, abstrair a unidade afetivo-cognitiva das relações sociais para então reposicioná-la, mesmo que brevemente, nas relações sociais de classe alienadas, porém num nível superior de compreensão e organização. Contudo, salienta-se que, ainda que a unidade afetivo-cognitiva da atividade consciente humana se manifeste concretamente imersa em relações sociais alienadas, o foco desta dissertação foi buscar compreendê-la teórico-metodologicamente priorizando, portanto, sua análise abstrata, isto é, momentaneamente isolada dessas relações. Sendo assim, buscou-se apresentar certas diretrizes preambulares para o estudo da unidade afetivo-cognitiva sob a égide de relações alienadas no modo de produção capitalista. Palavras-chave: unidade afetivo-cognitiva; atividade humana; consciência; Psicologia Histórico-Cultural.Abstract: This study, of theoretical and methodological nature, aimed to systematize the concept of affective-cognitive unity from perspective of the Cultural-Historical Psychology. This goal is justified by the lack of studies on this subject in psychology and the perception that there is a predominance of dualistic approaches regarding the relation of reason and emotion in psychological studies. In this sense, the study of affective-cognitive unity can bring increments to Psychology by discussing the methodological aspects of the separation between reason/emotion and demonstrating in detail the link between these processes as an essential part of the human process of apprehension and knowledge of reality. Therefore, we sought to situate methodologically the historical-dialectical materialism and the Cultural-Historical Psychology as a descendant of that method in order to, from this theoretical standpoint, study the constitution of human consciousness and the structure of activity as units of analysis of the affective-cognitive unity and understand the alienated human condition in capitalist class society. Thus, in accordance with Leontiev and Vygotsky, we analyzed the structure of human activity and the expression of the affective-cognitive unity through personal and social meanings, arriving at the expression of that unity in the constitution of the human personality. This investigation resulted in the conclusion that the structure of the activity and the constitution of human consciousness require affective-cognitive functions to form a subjective image of objective reality in the human psyche. Therefore, it was pointed out that, according to Vygotsky, to understand the affective-cognitive unity as semantic system of consciousness demands a detailed investigation of the relationship between human activity and the way in which the self renders this activity conscious. That was the main effort employed in this work, ie, abstract the affective-cognitive unity of social relations and then reposition it, however briefly, into the alienated class social relations, but in a higher level of understanding. Nevertheless, it is noted that, although the affective-cognitive unity present in the human conscious activity manifests itself concretely immersed in alienated social relations, the focus of this work was to seek to understand it theoretically and methodologically therefore prioritizing its abstract analysis, ie momentarily isolated from those relationships. Therefore, we sought to provide some initial guidelines for the study of affective-cognitive unity under the aegis of alienated relations in the capitalist mode of production. Keywords: affective-cognitive unity; human activity; consciousness; Cultural-Historical Psycholog

Melhoria da qualidade do atendimento aos usuários com hipertensão arterial e/ou diabetes na UBS/ESF Edimar Medeiros De Sousa, Cabeceiras Do Piauí, PI

As transições demográfica, nutricional e epidemiológica ocorridas no século passado determinaram um perfil de risco em que doenças crônicas como o diabetes e a hipertensão assumiram ônus crescente e preocupante. A quantidade de pessoas com Hipertensão Arterial Sistêmica e/ou Diabetes Mellitus encontradas no município de Cabeceiras do Piauí, PI, assim como no Brasil, é bastante alta, levando a um maior número de internações desnecessárias, tratamentos onerosos etc. O trabalho apresentado relata uma intervenção realizada na Unidade Básica de Saúde Edimar Medeiros de Sousa no município de Cabeceiras do Piauí, PI; no qual a população alvo foram os usuários com Hipertensão Arterial Sistêmica e/ou com Diabetes Mellitus de toda a área de abrangência do Programa de Saúde da família da referida Unidade de Saúde. A intervenção teve como objetivos: Melhorar o atendimento aos usuários com hipertensão e/ou diabetes; ampliar a cobertura de atendimento; melhorar a qualidade da atenção; melhorar a adesão de pessoas; melhorar o registro das informações; mapear pessoas com hipertensão e/ou diabetes para doença cardiovascular e promover a saúde da comunidade. As ferramentas utilizadas para coleta dos dados na intervenção foram as fichas espelho fornecidas pelo curso e os prontuários dos usuários, sendo os cadastros dos usuários refeitos e atualizados individualmente na ocasião do atendimento. Os resultados da intervenção na Unidade Básica de Saúde foram uma cobertura satisfatória da atenção aos usuários com Hipertensão Arterial Sistêmica e Diabetes Mellitus. Além disso, são perceptíveis as melhorias na qualidade da atenção ao usuário hipertenso e/ou diabético por meio da realização de cadastros adequados, do exame clínico e exames complementares em dia de acordo com o protocolo, da prescrição de medicamentos da farmácia popular, da avaliação da necessidade de atendimento odontológico e, especialmente, da oferta de orientações em ações educativas coletivas e individuais. Algumas dificuldades enfrentadas ao longo da intervenção, como a falta de recursos humanos e materiais, distância entre as localidades, falta de estrutura da unidade, falta de medicação, dentre outros, desafiaram a equipe e gestão. O enfrentamento desses impasses resultou em melhorias dos registros, bem como mais adesão destes usuários ao Programa. Conclui-se que estas ações foram de grande relevância para a comunidade, para a equipe e para a gestão, desta forma, espera-se que sejam realmente incorporadas à rotina do serviço, pois melhoram o atendimento e acompanhamento dos usuários