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The cellular prion protein (PrP

In the last years, a considerable amount of experimental evidence has highlighted the association between neurodegenerative disorders (NDD) and the biology of mitochondria-Endoplasmic Reticulum contacts (MERCs). In this review, we summarize the most recent findings on this topic. We underline that dysregulation of MERCs can contribute to the neurodegenerative process either by altering directly the functionality of neurons and their response to stress stimuli and metabolic shifts or by indirectly influencing the neuroinflammatory response that accompanies NDD. Our overview of the current literature suggest that defective MERCs could be a common determinant to the "hypergeneration" and "neurodegeneration" programs, leading respectively to tumours and NDD.

This article aims to propose an analysis of public policies that take into account the normative issues of justice. The starting point is the assumption that public policies have among their goals to promote justice. Public policies are understood as institutions that distribute goods and social resources and seek the realization of fundamental rights, a task that has an important impact on the distribution of goods and resources in society and thus in the mitigation of social inequality. Considering this premise, and coming from a brief presentation of main conceptions of justice for the developed reflection, this article proposes a substantive analysis of public policies and presents two perspectives from which they are to be carried out, one being institutionalist-procedural, and the other being based on the ideas and values that constitute the foundations of institutions and of the political action.Keywords: public policies; theory of justice; social justice. Este artigo tem como objetivo propor uma análise das políticas públicas que leve em consideração questões normativas de justiça. Seu ponto de partida é a assunção de que as políticas públicas têm dentre suas finalidades garantir a justiça social. Entende-se que as políticas públicas são instituições que distribuem bens e recursos sociais e são voltadas para a realização dos direitos fundamentais da cidadania, tarefa que tem importante impacto sobre a distribuição de bens e recursos em sociedade e portanto para a mitigação da desigualdade social. A partir dessa premissa e de uma breve apresentação de concepções de justiça basilares para a reflexão desenvolvida, este artigo propõe uma análise substantiva das políticas públicas a partir de concepções de justiça e apresenta duas perspectivas a partir das quais realizá-las, uma de cunho institucional-procedimentalista e, outra a partir das ideias e valores que são fundamento das instituições e da ação política.

Huntington disease (HD) is caused by the CAG (Q) expansion in exon 1 of the IT15 gene encoding a polyglutamine (poly-Q) stretch of the Huntingtin protein (Htt). In the wild type protein, the repeats specify a stretch of up 34 Q in the N-terminal portion of Htt. In the pathological protein (mHtt) the poly-Q tract is longer. Proteolytic cleavage of the protein liberates an N-terminal fragment containing the expanded poly-Q tract becomes harmful to cells, in particular to striatal neurons. The fragments cause the transcriptional dysfunction of genes that are essential for neuronal survival. Htt, however, could also have non-transcriptional effects, e.g. it could directly alter Ca2+ homeostasis and/or mitochondrial morphology and function. Ca2+ dyshomeostasis and mitochondrial dysfunction are considered important in the molecular aetiology of the disease. Here we have analyzed the effect of the overexpression of Htt fragments (18Q, wild type form, wtHtt and 150Q mutated form, mHtt) on Ca2+ homeostasis in striatal neuronal precursor cells (Q7/7). We have found that the transient overexpression of the Htt fragments increases Ca2+ transients in the mitochondria of cells stimulated with Ca2+-mobilizing agonists. The bulk Ca2+ transients in the cytosol were unaffected, but the Ca2+ content of the endoplasmic reticulum was significantly decreased in the case of mHtt expression. To rule out possible transcriptional effects due to the presence of mHtt, we have measured the mRNA level of a subunit of the respiratory chain complex II, whose expression is commonly altered in many HD models. No effects on the mRNA level was found suggesting that, in our experimental condition, transcriptional action of Htt is not occurring and that the effects on Ca2+ homeostasis were dependent to non-transcriptional mechanisms.

Intestinal failure is a multifaceted condition that may require high-complexity treatment and a multidisciplinary program, including home parenteral nutrition therapy (HPNT) and intestinal transplantation. In this article, we profile a Brazilian single-center experience with 128 cases of HTPN followed for the last 30 years and appraise the referral for potential intestinal and multivisceral transplantation.

AIMS: Pandemics impose large demands on the health care system. The supply of appropriate chemotherapeutic agents, namely oseltamivir solution, presented a serious challenge in the recent influenza pandemic. This study reports on the rational series of pharmacotechnical steps that were followed to appropriately handle bulk oseltamivir powder to meet the increased demand. METHODS: During a six-week period in August and September of 2009, a task force was created in the Central Pharmacy of Hospital das Clínicas to convert imported oseltamivir phosphate into ready-to-use solution for utilization by physicians and public health authorities. The protocol included dissolution, physico-chemical tests and the bottling of a liquid microdose formulation for emergency room and outpatient dispensing with adequate quality control during all phases. RESULTS: The successful production routine was based on a specially designed flowchart according to which a batch of 33210 g of oseltamivir powder was converted into 32175 solution units during the aforementioned period with a net loss of only 2.6%. The end products were bottles containing 50 ml of 15 mg/mL oseltamivir solution. The measured concentration was stable and accurate (97.5% - 102.0% of the nominal value). The drug was prescribed as both a prophylactic and therapeutic agent. DISCUSSION: Hospital pharmacies are conventionally engaged in the manipulation of medical prescriptions and specialty drugs. They are generally responsible for only small-scale equipment used for manufacturing and quality-control procedures. The compounding of oseltamivir was a unique effort dictated by exceptional circumstances. CONCLUSION: The shortage of oseltamivir solution for clinical use was solved by emergency operationalization of a semi-industrial process in which bulk powder was converted into practical vials for prompt delivery.

A internacionalização é um campo multidisciplinar. Suas práticas demonstram diversos comportamentos, modos e motivações para que o processo ocorra. Dessa forma, o objetivo desse estudo foi o de compreender quais fatores motivadores e facilitadores levaram a empresa Confase a internacionalizar-se. Os procedimentos metodológicos adotados no presente trabalho foram caracterizados como pesquisa qualitativa e descritiva utilizando a estratégia de estudo de caso sendo o nível de analise organizacional. Os resultados demonstraram que a Confase teve como principais motivações para se internacionalizar: (a) a quebra de rede de relacionamento; (b) posicionamento de mercado; (c) custos menores por meio da diferença cambial e o (d) client following. Já como facilitadores: incentivos governamentais e Know How. Como dificultadores, foi destacado como principal a burocracia. E quanto aos benefícios demonstrou-se que houve a superação de barreira protecionista. De certa forma, o processo de internacionalização pode ser descrito em quatro macro eventos como: (1) exportação indireta por meio de uma trading company, (2) identificação de oportunismo da rede de relacionamento, (3) quebra da rede de relacionamento, (4) abertura da Confase. Portanto considera-se que houve a identificação dos fatores que influenciaram a empresa.

Foi estudada a influência do intervalo entre cortes na produção de massa seca da parte aérea de duas espécies de capim limão. O experimento foi realizado no Instituto Agronômico, em Campinas-SP, 04 de junho/05 a 28 de agosto/06. O delineamento experimental utilizado foi em blocos ao acaso, com três repetições, com os tratamentos em esquema fatorial 2 x 4, sendo duas espécies (C. citratus e C. flexuosus) e quatro intervalos entre cortes (40; 60; 80 e 100 dias). Para C. flexuosus, maiores intervalos entre cortes proporcionaram maior massa seca acumulada ao longo do ciclo de cultivo, partindo de 329,04 para 704,16 g planta-1 de massa seca acumulada da parte aérea, para intervalos entre cortes de 40 e 100 dias, respectivamente. A espécie C. citratus apresentou resposta linear decrescente da massa seca acumulada da parte aérea quanto maior o intervalo entre cortes utilizado, produzindo 238,68 g planta-1 utilizando intervalo entre cortes de 40 dias.The aim of this study was to analyze the influence of the interval between cuts on the dry mass yield of the aerial part of two lemon grass species. The experiment was conducted at Agronomical Institute (IAC), in Campinas - SP, from June 4th, 2005 through August 28th, 2006. The experiment was carried out in a completely randomized block design, with three replications, and the treatments in a 2 x 4 factorial design, corresponding two species (C. citratus and C. flexuosus) and four intervals between cuts (40; 60; 80 and 100 days). For C. flexuosus, longer intervals between cuts generated more dry mass accumulated throughout the cultivation cycle, beginning on 329,04 to 704,16 g plant-1 of accumulated dry mass of the aerial part, for intervals between cuts of 40 and 100 days, respectively. The C. citratus species showed a decrease in its linear response for the accumulated dry mass of the aerial part the longer the interval between cuts was, yielding 238,68 g plant-1 for a 40 day interval between cuts.

A partir do método de custeio por absorção, com adaptação do custeio baseado em atividades, um sistema de informações foi modelado e implantado para monitorar custo de produção, dos produtos fabricados pela farmácia hospitalar do Hospital das Clínicas da Faculdade de Medicina da USP. Foram analisados os formulários dos produtos fabricados, insumos, gastos indiretos de fabricação, controle de qualidade e totalizados os tempos gastos da mão-de-obra direta de 100 produtos fabricados em julho de 2003. Os resultados mostraram que de 35 itens produzidos com similares, 28 apresentaram custo de produção inferior ao preço do fabricante no mercado, estimando que nesse mês o HC deixou de gastar, aproximadamente, 750 mil reais com a produção interna. Os 65 itens restantes eram produtos exclusivos e especiais. Os gastos com insumos corresponderam a 69% do custo total de produção. O modelo proposto mostrou que a farmácia hospitalar pode proporcionar redução de gastos à entidade. On the basis of the absorption costing method, with a number of adaptations from activity based costing, an information system was modeled and implanted to monitor the production costs of products manufactured by the hospital pharmacy of Hospital das Clínicas, Faculty of Medicine, University of São Paulo. Were analysed manufactured products forms, raw material, indirect manufacturing costs, quality control, and added up direct labor time for 100 manufactured products in July 2003. The results showed that out of 35 items produced with similar products in the market, 28 presented a production cost below the price of the market manufacturer. Evaluations revealed that, during this month, the institution saved about 750 thousand reais through internal production. The 65 remaining items were exclusive and special products. Raw material expenses accounted for 69% of total production costs. The proposed model showed that the hospital pharmacy can lead to expense reduction for the entity.

The cellular prion protein (PrPC) is a cell surface glycoprotein predominantly expressed in the central nervous system. A modification of the mainly α-helical PrPC into an isoform enriched in β-strands generates the prion, the infectious particle at the basis of fatal prion diseases. In spite of PrPC’s intimate involvement in prion propagation, its physiological function remains enigmatic. Past observations have supported the possibility that PrPC regulates Ca2+ homeostasis, a notion that has been recently reinforced by the demonstration that PrPC controls Ca2+ fluxes in domains close to the neuronal plasma membrane, and interacts physically with a ionotropic glutamate receptor, thus protecting from glutamate excitotoxicity. Recently, however, it has been proposed that PrPC serves as a high-affinity receptor for soluble amyloid-β (Aβ) oligomers implicated in Alzheimer’s disease (AD), and this interaction could thus be crucial for AD-related synaptic dysfunctions. In light of this background, using genetically-encoded Ca2+ probes targeting different cell domains of cerebellar granule neurons expressing, or not, PrPC, this work focused on whether PrPC regulates local Ca2+ fluxes arising from the activation of storeoperated Ca2+ entry (SOCE), and/or of glutamate receptors. We found that, with respect to PrPC-expressing neurons, the absence of PrPC caused alterations of several local Ca2+ fluxes, indicating that PrPC could act as a key component of the system(s) controlling neuronal Ca2+ homeostasis. As to the molecular mechanism enabling PrPC to exert such control, the results showed the implication of Fyn tyrosine kinase and of the Ca2+-induced-Ca2+-release from the ryanodine receptor. The study has also analyzed whether soluble Aβ oligomers could affect the PrPC-dependent regulation of Ca2+ homeostasis. Obtained results have shown that the acute treatment of neurons with Aβ oligomers abrogates the control of PrPC over Fyn and SOCE, and alters mitochondrial Ca2+ uptake after stimulation of ionotropic glutamate receptors. This data thus suggests a PrPC-dependent mechanism for Aβ-induced neuronal Ca2+ dyshomeostasis.

PNKP (polynucleotide kinase 3'-phosphatase, OMIM #605610) product is involved in the repair of strand breaks and base damage in the DNA molecule mainly caused by radical oxygen species. Deleterious variants affecting this gene have been previously associated with microcephaly, epilepsy, and developmental delay.(1) According to a previous report, homozygous loss-of-function substitution in PNKP was associated with cerebellar atrophy, neuropathy, microcephaly, epilepsy, and intellectual disability.(2) Recently, whole-exome sequencing (WES) performed in a cohort of Portuguese families with ataxia with oculomotor apraxia (AOA) disclosed pathogenic variants in PNKP in 11 individuals. Other clinical features in that study included neuropathy, dystonia, cognitive impairment, decreased vibration sense, pyramidal signs, mild elevation in α-fetoprotein, and low levels of albumin. This condition was named AOA type 4 (OMIM #616267), as the phenotype of AOA has been previously associated with 3 other genes: APTX, SETX, and PIK3R5.(3) Altogether, these reports demonstrate the great phenotypic diversity associated with PNKP mutations. In this article, we further enlarge this variability by demonstrating that early-onset axonal sensory-motor neuropathy (or axonal Charcot-Marie-Tooth (CMT) disease) followed years later by ataxia without oculomotor apraxia can be caused by deleterious variants in PNKP. Full consent was obtained from the patient and his parents for this publication. This study was approved by institutional ethics committees.

Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

Resenha de The Power of Tolerance: A Debate (Wendy Brown & Rainer Forst, 2014).

A “Idéias” – Revista do Instituto de Filosofia e Ciências Humanas – da Unicamp abre a edição do primeiro semestre de 2011 com o Dossiê “Migrações”, esse contou com a colaboração de pesquisadores que tem no cerne de suas reflexões essa temática. As migrações assumem grande relevância no contexto contemporâneo dado ao impacto que causam as sociedades de origem e destino. O conjunto de questões sociais, econômicas e culturais que as migrações trazem à baila oferece aos pesquisadores e interessados um material rico e estimulante as reflexões. As “idas” e “vindas” dos migrantes apresenta-nos a relativização de perspectivas quando não a criação de novos espaços sociais de vida.

Made available in DSpace on 2022-04-29T08:49:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-10-29 This work discuss a methodology for evaluating the hydrogeological potential in the area of Residential Condominium Villa Verde, in Araçariguama - SP municipality, based on the analysis and the intersection of historical information, bibliographic references, remote sensing and geology. There are two boreholes in Villa Verde, the first one drilled during the construction of Villa Verde and the second one did in 2002 when the first borehole could not support the demand for water in Villa Verde any more. The borehole was perforated after a geological and geophysical study in the area to determine it's the best location, however it did not produce water. Geologically the studied area is located over the São Roque granitoid and the metasediments of Serra do Itaberaba Formation (shales). Because of this geological context the aquifer model considered is fractured, what made important emphasize the discontinuity in the structural characterization of bedrock. This study had a practical focus that aimed the definition of potential structures that could be able to have a fractured aquifer, indicating the areas for a detailed prospective study, which can be direct (drilling) or indirect (ground geophysics). Universidade Estadual Paulista Julio de Mesquita Filho - UNESP, Campus de Rio Claro. Avenida 14A, 535 - Bairro, Vila Indaiá, CEP: 13506 - 535. Rio Claro - SP Universidade Estadual Paulista Julio de Mesquita Filho - UNESP, Campus de Rio Claro. Avenida 24, 1515 - Bairro, Bela Vista. CEP: 13506-900. Rio Claro - SP Universidade Estadual Paulista Julio de Mesquita Filho - UNESP, Campus de Rio Claro. Avenida 14A, 535 - Bairro, Vila Indaiá, CEP: 13506 - 535. Rio Claro - SP Universidade Estadual Paulista Julio de Mesquita Filho - UNESP, Campus de Rio Claro. Avenida 24, 1515 - Bairro, Bela Vista. CEP: 13506-900. Rio Claro - SP

El presente libro recoge intervenciones, ponencias y comunicaciones, presentadas en el Simposio: INEQUIDADES EN LA PRESTACION DE SERVICIOS DE SALUD EN LATINOAMÉRICA Y EL CARIBE celebrado dentro del II CONGRESO CIENCIAS, TECNOLOGÍAS Y CULTURAS, los días 29 octubre a 1 de noviembre 2010. El Congreso fue organizado y tuvo su sede en la Universidad de Santiago, Chile. El Simposio tuvo el auspicio de la Red Latinoamericana de Historiadores en Ciencias de la Salud y de la Federación Latinoamericana y del Caribe de Instituciones de Bioética (FELAIBE). 1-248 galcantara@ula.ve

The plasma membrane Ca(2+) ATPases (PMCA pumps) cooperate with other transport systems in the plasma membrane and in the organelles in the regulation of cell Ca(2+). They have high Ca(2+) affinity and are thus the fine tuners of cytosolic Ca(2+). They belong to the superfamily of P-type ATPases: their four basic isoforms share the essential properties of the reaction cycle and the general membrane topography motif of 10 transmembrane domains and three large cytosolic units. However they also differ in other important properties, e.g., tissue distribution and regulatory mechanisms. Their chief regulator is calmodulin, that removes their C-terminal cytosolic tail from autoinhibitory binding sites next to the active site of the pump, restoring activity. The number of pump isoforms is increased to over 30 by alternative splicing of the transcripts at a N-terminal site (site A) and at site C within the C-terminal calmodulin binding domain: the splice variants are tissue specific and developmentally regulated. The importance of PMCAs in the maintenance of cellular Ca(2+) homeostasis is underlined by the disease phenotypes, genetic or acquired, caused by their malfunction. Non-genetic PMCA deficiencies have long been considered possible causative factors in disease conditions as important as cancer, hypertension, or neurodegeneration. Those of genetic origin are better characterized: some have now been discovered in humans as well. They concern all four PMCA isoforms, and range from cardiac dysfunctions, to deafness, to hypertension, to cerebellar ataxia.

Aims: Monoamine oxidases (MAOs) are mitochondrial flavoenzymes responsible for neurotransmitter and biogenic amines catabolism. MAO-A contributes to heart failure progression via enhanced norepinephrine catabolism and oxidative stress. The potential pathogenetic role of the isoenzyme MAO-B in cardiac diseases is currently unknown. Moreover, it is has not been determined yet whether MAO activation can directly affect mitochondrial function. Results: In wild type mice, pressure overload induced by transverse aortic constriction (TAC) resulted in enhanced dopamine catabolism, left ventricular (LV) remodeling, and dysfunction. Conversely, mice lacking MAO-B (MAO-B−/−) subjected to TAC maintained concentric hypertrophy accompanied by extracellular signal regulated kinase (ERK)1/2 activation, and preserved LV function, both at early (3 weeks) and late stages (9 weeks). Enhanced MAO activation triggered oxidative stress, and dropped mitochondrial membrane potential in the presence of ATP synthase inhibitor oligomycin both in neonatal and adult cardiomyocytes. The MAO-B inhibitor pargyline completely offset this change, suggesting that MAO activation induces a latent mitochondrial dysfunction, causing these organelles to hydrolyze ATP. Moreover, MAO-dependent aldehyde formation due to inhibition of aldehyde dehydrogenase 2 activity also contributed to alter mitochondrial bioenergetics. Innovation: Our study unravels a novel role for MAO-B in the pathogenesis of heart failure, showing that both MAO-driven reactive oxygen species production and impaired aldehyde metabolism affect mitochondrial function. Conclusion: Under conditions of chronic hemodynamic stress, enhanced MAO-B activity is a major determinant of cardiac structural and functional disarrangement. Both increased oxidative stress and the accumulation of aldehyde intermediates are likely liable for these adverse morphological and mechanical changes by directly targeting mitochondria. Antioxid. Redox Signal. 20, 267–280.

Orientador: Valeriano Mendes Ferreira Costa Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Filosofia e Ciências Humanas Resumo: Esta tese realiza uma análise do Sistema Único de Saúde (SUS) brasileiro a partir da teoria da justiça como equidade proposta por John Rawls. O ponto de partida da análise que fundamenta a definição da saúde como uma questão de justiça é a concepção ralwsiana de sociedade justa elaborada em Uma Teoria da Justiça (2008). Em diálogo com a argumentação e com o debate suscitado pela obra de Rawls, verificamos como a saúde surge como questão através da crítica à teoria rawlsiana elaborada por Amartya Sen e Martha Nussbaum. Ambos os autores, em face da "negligência" de Rawls perante o tema, afirmam que a saúde deve ser entendida como um bem de importância moral fundamental em razão das desigualdades a ela atreladas. Mas é principalmente no trabalho de Norman Daniels, que se constrói em dialogo com o de John Rawls e com o de Amartya Sen, que esta tese se baseia para fundamentar o argumento de que a saúde deve ser tratada como uma questão de justiça e que, apesar de ela não ter sido especificamente tratada pela teoria da justiça de Rawls, uma extensão de sua teoria pode se realizar a partir seus princípios da justiça, em especial do princípio da Igualdade Equitativa de Oportunidades, sem prejuízos para sua formulação. A argumentação desta tese prossegue abordando, ainda sob perspectiva normativa, duas questões fundamentais para a compreensão do SUS a partir da justiça do sistema: a primeira é a democracia e sua relação com a justiça, debate que se faz necessário dadas as características do Estado e da sociedade brasileira e, também, dado o processo de formação e implementação do sistema de saúde brasileiro; a segunda, a análise de políticas públicas baseada no método proposto por Bo Rothstein que, preocupado com a justiça das instituições, volta-se para a substância da política sem desconsiderar seu processo. É sobre esse pano de fundo de normativo, parâmetro a partir do qual é possível definir saúde e pensar uma política de saúde justa, que a análise se volta para o SUS com o intuito de identificar elementos que permitam responder sobre a justiça do sistema. Para a análise do SUS, elencamos alguns pontos/questões fundamentais: sua trajetória e sua definição de saúde, que abarca o papel da noção de Determinantes Sociais da Saúde na formulação da política e enquanto critério de justiça; os princípios definidores do SUS: universalidade, integralidade, igualdade, gratuidade, descentralização e participação popular; por fim, a relação que se estabelece entre o setor privado/suplementar e o público/complementar. Esse caminho foi percorrido com o propósito de identificar as concepções de justiça do sistema que, somadas a um parâmetro normativo de saúde justa, fornecem-nos elementos para responder sobre a justiça dos resultados alcançados pelo SUS Abstract: This thesis studies the Brazilian health system, SUS (Sistema Único de Saúde/Unified Health System), through John Rawls? theory of justice as fairness . It?s the rawlsian conception of a just society presented in his book, Uma Teoria da Justiça ([A Theory of Justice] 2008), that supports the definition of health as a matter of justice adopted here. Establishing a dialogue with the discussion toward Rawls? works, we verified how health emerges as a central question in Amartya Sen?s and Martha Nussbaum?s criticisms to Rawls? theory. Both authors state, regarding Rawls negligence toward the theme, that health is a good with a fundamental moral importance, considering the iniquities related to it. But it?s mainly in Norman Daniels? works, done in dialogue with John Rawls? and Amartya Sen?s works, that this thesis rely on to state that health is a matter of justice and that an extension of Rawls theory can be made from his principles of justice, mostly from the principle of fair equality of opportunity. Keeping a normative stand point, this thesis? argumentation continues to deal with two main questions to the understanding of the Unified Health System justice: the first one is democracy and its relation with justice, a necessary discussion, considering the features of the Brazilian State and its society, as well as the formation and implementation process of the health system; the second is the public policies analysis based on the method proposed by Bo Rothstein, who, concerned with the institutions justice, turned to the policy?s substance without neglecting its process. It is over this normative background, parameter through which it?s possible to define and think of a just health policy, that the analysis seeks to identify in SUS elements which allows us to answer about the system justice. For its analysis, we chose some fundamental points: its history and its health definition, which embodies the Social Determinants of Health in the policy formulation and as a justice criterion; the principles of SUS: universality, integrality, egalitarianism, gratuitousness, decentralized policy management and public participation; and finally, the relationship between the private/supplementary and the public/complementary sectors. The aim here was to identify the system?s conceptions of justice that, combined with a normative parameter of just health, supplies us with arguments to answer about the justice of the results achieved by SUS Doutorado Ciências Sociais Doutora em Ciências Sociais

O dossiê “Políticas Públicas no Brasil: uma agenda de pesquisa” é fruto de um seminário com o mesmo título realizado pelo Núcleo de Estudos de Políticas Públicas (NEPPs), vinculado à Faculdade de Ciências Humanas e Sociais da Universidade Estadual Paulista – Unesp, campus de Franca. O Núcleo é cadastrado junto ao Conselho Nacional de Desenvolvimento Científi co e Tecnológico (CNPq) desde o ano de 2006, sendo composto por docentes, pesquisadores e estudantes de diferentes áreas do conhecimento: Ciência Política, Serviço Social, Sociologia, Ciências Econômicas, Geografi a, Direito, Demografi a e Relações Internacionais. Tem o objetivo de fortalecer o debate sobre as políticas públicas no âmbito da Universidade e fora dela, assim como, realizar trabalhos práticos em linhas fundamentais de pesquisa: Políticas Públicas: fundamentos, métodos e análise; Políticas Públicas e desenvolvimento; Políticas Públicas e Integração regional; Políticas Públicas e justiça social; e Políticas Públicas e Paradiplomacia.

Hearing relies on the ability of the inner ear to convert sound waves into electrical signals. The main actors in this process are hair cells. Their stereocilia contain a number of specific proteins and a scaffold of actin molecules. They are organized in bundles by tip-link filaments composed of cadherin 23 and protocadherin 15. The bundle is deflected by sound waves leading to the opening of mechano-transduction channels and to the influx of K(+) and Ca(2+) into the stereocilia. Cadherin 23 and the plasma membrane calcium ATPase isoform 2 (PMCA2) are defective in human and murine cases of deafness. While the involvement of cadherin 23 in deafness/hearing could be expected due to its structural role in the tip-links, that of PMCA2 has been discovered only recently. This review will summarize the structural and functional characteristics of hair cells, focusing on the proteins whose mutations may lead to a deafness phenotype.

Background: According to the World Health Organisation, Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial agent worldwide.The aim of the present study was to determine the prevalence and risk factors for genital infection with Ct among sexually active women (14-60 years of age), in Turin (northern Italy).Methods: A cross-sectional study was performed between January 2002 and December 2007 among sexually active women in Turin. All women were tested for Ct infection using the Amplified Ct Assay (Gen-Probe) on an endocervical specimen. The prevalence was calculated as the proportion of Ct-positive women out of the total study population. Associations between Ct infection and risk factors (socio-demographic, behavioural, and clinical-gynaecological) were analyzed using the Chi-square test. The level of significance was set at 0.05. Risk factors independently associated with Ct infection were determined using a multivariate logistic regression model. The statistical analyses were performed using SPSS (version 17.0).Results: The study included 25,289 women, of whom 1.8% were found to have Ct infection. The prevalence of Ct infection increased significantly from 1.5% in 2002 to 2.2% in 2007 (χ2 =5.6; p-value In the multivariate analysis, Ct infection was significantly associated with an adjusted odds ratio higher than 2 for young age (14-24 years), being non-Italian, having had 2 or more lifetime sexual partners, and having had more than 1 partner in the previous six months.Conclusions: Our results showed an increase in Ct prevalence in Turin between 2002 and 2007. A significantassociation between Ct infection and young age, multiple sexual partners, and originating from Eastern Europe was observed. To reduce the spread of the infection, women with at least one of the above mentioned risk factors, should be encouraged to undergo a free-of-charge Ct testing.

The inner ear converts sound waves into hearing signals through the mechanoelectrical transduction (MET) process. Deflection of the stereocilia bundle of hair cells causes the opening of channels that allow the entry of endolymph K(+) and Ca(2+). Ca(2+) that enters is crucial to the hearing process and is exported to the endolymph by the plasma membrane Ca(2+) pump (isoform PMCA2w/a): disturbances of the balance between Ca(2+) penetration and ejection, e.g. by pump mutations, generate deafness. Hearing loss caused by PMCA defects is frequently exacerbated by mutations in cadherin 23, a single pass stereociliar Ca(2+) binding protein that forms the tip links which permit the deflection of the stereocilia bundle and thus the opening of the MET channels. The PMCA2w/a pump ejects Ca(2+) to the endolymph even in the absence of the natural activator calmodulin. This satisfies the special Ca(2+) homeostasis requirements of the stereocilia/endolymph system. Here we have analyzed a mice and a human previously described pump mutant. The human mutant only exacerbated the deafness produced by a cadherin 23 mutation. The murine mutant overexpressed in model cells displayed an evident defect both in the basal activity of the pump and in the long range ejection of Ca(2+), the human mutant instead failed to impair the Ca(2+) ejection by the pump.

Made available in DSpace on 2014-06-11T19:26:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-25Bitstream added on 2014-06-13T18:29:46Z : No. of bitstreams: 1 demario_afg_me_rcla.pdf: 2466919 bytes, checksum: 86b229ab00f7afbb9a69e932288cdeb7 (MD5) Este trabalho discute o emprego dos métodos geofísicos no estudo de águas subterrâneas no município de Araçariguama-SP na área do Condomínio Residencial Villa Verde que está geologicamente localizado sobre o Granitóide São Roque e os metassedimentos da Formação Serra do Itaberaba (xistos argilosos). Diante deste contexto geológico o modelo de aqüífero considerado na área do condomínio é o fraturado, tornando-se importante a caracterização estrutural do maciço rochoso com ênfase nas descontinuidades. No condomínio Villa Verde existem dois poços artesianos, sendo que o primeiro foi feito durante a construção do condomínio e o segundo poço foi perfurado em 2002, quando o consumo de água do condomínio se tornou maior que a capacidade de produção do primeiro poço. Após a realização de um estudo geológico e geofísico para determinar a melhor localização do poço na área do condomínio, ele foi locado e perfurado, mas o poço não produziu água. Visando a problemática da água na região e as dificuldades de exploração em ambiente de aqüífero fraturado, este trabalho buscou integrar estudos geológicos e estruturais com dados de poços perfurados na região, com o intuito de dar suporte à programação e interpretação dos ensaios geofísicos. Os estudos desenvolvidos neste trabalho tiveram um foco prático e voltado para a definição de estruturas com potencial para abrigar um aqüífero do tipo fraturado, utilizando a geofísica como ferramenta para investigar essas estruturas em subsuperficie, auxiliando na avaliação de viabilidade do alvo definido que, para este estudo, foi o Condomínio Villa Verde This work discuss the use of geophysics methods in the study of groundwater in the city of Araçariguama – SP, specifically in the area of Condomínio Residencial Villa Verde that is geologically located over the São Roque granitoid and the shales of Serra do Itaberaba Formation. Because of this geological context, the considered aquifer model is fractured, making important emphasize the descontinuity in the structural characterization of bedrock. There are in the Villa Verde two boreholes, the first one was done during the construction of Villa Verde and the second one was drilled in 2002 when the first borehole could not support the demand for water in Villa Verde anymore. After a geological and geophysical study in the area to determine the best location for the borehole, it was perforated but did not produced water. Considering the problems with water in this area and the exploration difficulties of fractured aquifers, this work seeks the integration of geological and structural studies with dates boreholes in the region where the area is located. The aim is support the interpretation and program of geophysical survey. This study had a practical focus that aimed the definition of potential structures able to have a fractured aquifer. The use here of geophysics as a resource to investigate these structures in the ground intend to be an auxiliary to evaluate the viability of defined target, which for this study were the “Condomínio Villa Verde”