From diabetes to heart disease : studies on dyslipidemia-induced B-cell dysfunction, immunomodulation in heart transplantation, and cardiac stem cell therapy

Diabetes is a growing epidemic with devastating human, social and economic impact. It is associated with significant changes in plasma concentrations of lipoproteins. We tested the hypothesis that lipoproteins modulate the function and survival of insulin-secreting cells. We first detected the presence of several receptors that participate in the binding and processing of plasma lipoproteins and confirmed the internalization of fluorescent LDL and HDL particles in insulin-secreting β-cells. Purified human VLDL and LDL particles reduced insulin mRNA levels and β-cell proliferation, and induced a dose-dependent increase in the rate of apoptosis. In mice lacking the LDL receptor, islets showed a dramatic decrease in LDL uptake and were partially resistant to apoptosis caused by LDL. VLDL-induced apoptosis of β-cells involved caspase-3 cleavage and reduction in levels of the c-Jun N-terminal (JNK) Interacting Protein-1 (IB1/JIP-1). In contrast, the pro-apoptotic signaling of lipoproteins was antagonized by HDL particles or by a small peptide inhibitor of JNK. The protective effects of HDL were mediated, in part, by inhibition of caspase-3 cleavage and activation of the protein kinase Akt/PKB. Heart disease is a major cause of morbidity and mortality among patients with diabetes. When heart failure is refractory to medical therapy and cannot be improved by electrical resynchronization, percutaneous angioplasty or coronary graft bypass surgery, heart transplantation remains a "last resort" therapy. Nevertheless, it is limited by the side effects of immunosuppressive drugs and chronic rejection. Localized expression of immunomodulatory genes in the donor organ can create a state of immune privilege within the graft, and was performed in rodent hearts by infecting cells with an adenovirus encoding indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the catabolism of tryptophane. Other strategies are based on genetic manipulation of dendritic cells (DCs) with immunosuppressive genes and in vitro exposure of DCs to agents that prevent their maturation by inflammatory cytokines. Finally, we used 5-bromo-2'-deoxyuridine, which is incorporated into DNA and diluted with cell division, to identify long-term label retaining cells in the adult rodent heart. The majority of these cells were positive for the stem cell antigen-1 (Sca-1) and negative for the endothelial precursor marker CD31. They formed cardiospheres in vitro and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. Taken together, these data provide evidence of slow-cycling stem cells in the rodent heart. Chronic shortage of donor organs opens the way to cardiac stem cell therapy in humans, although the long way from animal experimentation to routine therapy in patients may still take several years. - Du diabète de type 2 à la maladie coronarienne : trois études sur les dysfonctions de la cellule sécrétrice d'insuline induites par les dyslipidémies, l'immunomodulation dans la transplantation cardiaque, et la thérapie par des cellules souches myocardiques. Le diabète de type 2 a pris les dimensions d'une épidémie, avec des conséquences sociales et économiques dont nous n'avons pas encore pris toute la mesure. La maladie s'accompagne souvent d'une dyslipidémie caractérisée par une hypertriglycéridémie, des taux abaissés de cholestérol HDL, et des concentrations de cholestérol LDL à la limite supérieure de ce qui est considéré comme acceptable. L'hypothèse à la base de cette étude est qu'une modification des taux plasmatiques de lipoprotéines pourrait avoir une influence directe sur la cellule β sécrétrice d'insuline en modifiant sa fonction, sa durée de vie et son taux de régénération. Dans un premier temps, nous avons mis en évidence, sur la cellule β, la présence de plusieurs récepteurs impliqués dans la captation des lipoprotéines. Nous avons confirmé la fonctionnalité de ces récepteurs en suivant l'internalisation de LDL et de HDL marqués. En présence de VLDL ou de LDL humains, nous avons observé une diminution de la transcription du gène de l'insuline, une prolifération cellulaire réduite, et une augmentation de l'apoptose, toutes fonctions de la dose et du temps d'exposition. L'apoptose induite par les VLDL passe par une activation de la caspase-3 et une réduction du taux de la protéine IB1/JIP-1 (Islet Brain1/JNK Interacting Protein 1), dont une mutation est associée à une forme monogénique de diabète de type 2. Par opposition, les HDL, ainsi que des peptides inhibiteurs de JNK, sont capables de contrer la cascade pro-apoptotique déclenchée, respectivement, par les LDL et les VLDL. Ces effets protecteurs comprennent l'inhibition du clivage de la caspase-3 et l'activation de la protéine kinase Akt/PKB. En conclusion, les lipoprotéines sont des éléments clés de la survie de la cellule β, et pourraient contribuer au dysfonctionnement observé dans le pancréas endocrine au cours du développement du diabète. La maladie cardiaque, et plus particulièrement la maladie coronarienne, est une cause majeure de morbidité et de mortalité chez les patients atteints de diabète. Plusieurs stratégies sont utilisées quotidiennement pour pallier les atteintes cardiaques: traitements médicamenteux, électromécaniques par resynchronisation électrique, ou communément appelés « interventionnels » lorsqu'ils font appel à l'angioplastie percutanée. La revascularisation du myocarde par des pontages coronariens donne également de très bons résultats dans certaines situations. Il existe toutefois des cas où plus aucune de ces approches n'est suffisante. La transplantation cardiaque est alors la thérapie de choix pour un nombre restreint de patients. La thérapie génique, en permettant l'expression locale de gènes immunomodulateurs dans l'organe greffé, permet de diminuer les réactions de rejet inhérentes à toute transplantation (à l'exception de celles réalisées entre deux jumeaux homozygotes). Nous avons appliqué chez des rongeurs cette stratégie en infectant le coeur greffé avec un adénovirus codant pour l'enzyme indoleamine 2,3-dioxygénase (IDO), une enzyme clé dans le catabolisme du tryptophane. Nous avons procédé de manière identique in vitro en surexprimant IDO dans les cellules dendritiques, dont le rôle est de présenter les antigènes aux lymphocytes Τ du receveur. Des expériences similaires ont été réalisées en traitant les cellules dendritiques avec des substances capables de prévenir, en partie du moins, leur maturation par des agents pro-inflammatoires. Finalement, nous avons exploré une stratégie utilisée couramment en hématologie, mais qui n'en est encore qu'à ses débuts au niveau cardiaque : la thérapie par des cellules souches. En traitant des rongeurs avec un marqueur qui s'incorpore dans l'ADN nucléaire, le 5-bromo- 2'-deoxyuridine, nous avons identifié une population cellulaire se divisant rarement, positive en grande partie pour l'antigène embryonnaire Sca-1 et négative pour le marqueur endothélial CD31. En culture, ces cellules forment des cardiosphères et sont capables de se différencier dans les principaux types tissulaires mésenchymateux. Dans un milieu de differentiation adéquat, ces cellules expriment des gènes cardiomyocytaires. En résumé, ces données confirment la présence chez le rongeur d'une population résidente de précurseurs myocardiques. En addenda, on trouvera deux publications relatives à la cellule β productrice d'insuline. Le premier article démontre le rôle essentiel joué par la complexine dans l'insulino-sécrétion, tandis que le second souligne l'importance de la protéine IB1/JIP-1 dans la protection contre l'apoptose de la cellule β induite par certaines cytokines.

Health for life : annual report of activities for the period January-December 2013

In Seychelles, cardiovascular diseases (CVD), notably stroke, ischemic heart disease and hypertensive heart disease has become the largest contributor of deaths (40%) in the entire population. CVD also results in a large burden of disability and also has subsequent social and economic impact. The Unit for Prevention and Control of Cardiovascular Diseases (UPCCD) provides leadership, expertise and capacity at national level for the surveillance, prevention and control of cardiovascular diseases through education, programs and input into policy.

Supply Multipliers in Two Regional Economies

This paper focuses on the analysis of the economic impact that sectorial total factor productivity – or valued added - gains have on two regional Spanish economies (Catalonia and Extremadura). In particular it is studied the quantitative effect that each sector’s valued added injections has on household welfare (real disposable income), on the consumption price indices and factor relative prices, on real production (GDP) and on the government and foreign net income. To do that, we introduce the concept of supply multiplier. The analytical approach consists of a computable general equilibrium model, in which it is assumed perfect competition and cleared markets of goods and factors. All the parameters and exogenous variables of the model are calibrated by means of two social accounting matrices, one for each region under study. The results allow identifying those sectors with the greatest multipliers impact on consumer welfare as the key sectors in the regional economies. Keywords: efficiency gains, supply multipliers, key sectors, computable general equilibrium. JEL Classification: C68, R13.

La evaluación de la creatividad publicitaria en el ámbito docente. Análisis teórico y proyecto de investigación

La docencia de la creatividad publicitaria convive con diversas contradicciones y vacíos. Si esto es propio de cualquier materia de estudio, aquí se suma el peculiar curso científico tanto de la creatividad como de la publicidad, dos fenómenos de descomunal repercusión social, cultural y económica, aparentemente asequibles, pero en gran medida desconocidos.El presente trabajo indaga en la posibilidad de sistematizar la evaluación de la creatividad publicitaria y estima el valor docente de dicha sistematización. En una primera fase se exploran los ámbitos de referencia que afectan al tópico, así comolas conexiones que establecen entre ellos, en la esfera académica y profesional. A continuación se orientan y discuten los hallazgos de la prospección, se formula una hipótesis y se diseña una investigación que conduzca a validarla o refutarla.

La gestió de les destinacions i les noves mobilitats turístiques

Amb l’objectiu d’analitzar i comprendre d’una manera més adequada els mecanismes pels quals els potencials turistes que venen d’Anglaterra prenen la decisió de viatjar fins la Costa Daurada, en el context de la introducció de les línies aèries de baix cost a Espanya i la creació de noves rutes, s’ha dut a terme una enquesta a l’aeroport de Reus a un total de 445 turistes que estaven a punt de tornar de les seves vacances cap a Anglaterra tenint l'aeroport d'East Midlands (EMA) com a destinació i viatjant amb la companyia aèria de baix cost RyanAir. Amb el mètode utilitzat en aquest projecte s'ha mesurat, per mitjà de l'enquesta esmentada, el pes de la causalitat entre la presència de vols barats des de EMA fins a Reus amb la decisió dels turistes de passar les seves vacances en una regió turística de primer ordre a Catalunya com és la Costa Daurada. Segons els resultats de les dues preguntes causals que formen part de l’enquesta (pregunta 18 i pregunta 19), gairebé un 30% de l'impacte econòmic turístic total és degut a la disponibilitat de vols barats mitjançant RyanAir. Tanmateix, al voltant d’un 60% de l'impacte estaria relacionat amb el fet que els turistes visitarien la Costa Daurada independentment de la disponibilitat de vols de RyanAir. Això indicaria que tot i que els vols de Ryanair són innegablement atractius pels turistes, hi ha un desig important de visitar la Costa Daurada que podria ser satisfet per altres mitjans.

A Percepção da População Local Sobre os Impactos Económicos do Turismo na Ilha de São Vicente

A actividade turística só faz sentido, e torna-se viável, quando se proporciona uma experiência qualitativa aos principais agentes envolvidos, isto é, quando haja a optimização da experiência turística, a conservação ambiental e cultural e a inclusão social, pela participação activa das comunidades locais. Assim, esta monografia debruça-se sobre a análise de um desses pilares, mais concretamente, a população local, e como tal, objectiva-se analisar a sua percepção sobre os impactos económicos do turismo no desenvolvimento da ilha de São Vicente. Contudo, para dar uma resposta coerente à problemática deste estudo, que é identificar os impactos económicos do turismo percebido pelos residentes, recorreu-se à uma abordagem económica do turismo, tendo em conta as nomenclaturas desenvolvidas no âmbito da Conta Satélite do Turismo. Na avaliação dos impactos, fez-se a aplicação de um inquérito por questionário, dirigido aos residentes das zonas de Norte Baía, Ribeira de Calhau, São Pedro e o Centro da Cidade. Definiu-se uma amostra representativa de 200 indivíduos, analisando a relação entre o turismo e um conjunto de variáveis económicas tais como o emprego, o rendimento, as receitas governamentais, as infra-estruturas, a sazonalidade, os investimentos, e a inflação. Pelos resultados obtidos, concluiu-se que o turismo contribui positivamente para aumentar o emprego, o rendimento, melhorar a qualidade de vida, o aparecimento de novas empresas, o aumento do Produto Interno Bruto e ainda contribui para o desenvolvimento económico da ilha. Contudo, os resultados permitiram concluir que a ilha não depende, do ponto de vista económico, exclusivamente do turismo. Touristic activity only makes sense and becomes profitable when it brings a qualitative experience to the parties involved, i.e. when it results in an improvement of the touristic experience, with an environmental and cultural protection and social inclusion, through the active participation of the local communities, we developed this monograph based on the analysis of the people´s perception about the economic impact of the tourism in the development of São Vicente island. However, in order to have a coherent answer to the issues this document is concerned with, i.e to identify the economic impact of the tourism on people´s live, we went through an economic approach of the tourism, taking in consideration the nomenclature developed in the sphere of Tourism Satellite Account. For the evaluation of the impact we resorted to an enquiry to the residents of Norte Baía, Ribeira de Calhau, São Pedro, and Mindelo. A representative sample of 200 individuals has been defined, to analyze the relationship between the tourism itself and several economic targets, such as: employment, profits, infrastructure, season, investment, inflation. According to the analysis we concluded that the tourism has positively contributed to the uprising of new enterprise, to the increasing of the gross domestic product, to rise up the employment rate, to increase family´s incomes and consequently a better life quality and also to the economic development of São Vicente Island. Nevertheless we also concluded that economically São Vicente does not depend only on the tourism incomes.

Socioeconomic Effects of Gambling on Iowans Study Committee, 2004

Overview. The Studies Committee received an in-person progress report from the consultants retained by the Legislature to conduct a study of the socioeconomic effects of gambling on Iowans. Dr. Deepak Chhabra and Dr. Gene Lutz, both of the University of Northern Iowa, presented an update on the conduct of the study. Gambling Study Description. The consultants indicated that the study objectives are to determine the economic impact of gambling at existing Iowa casinos on the local community, the socioeconomic characteristics of gamblers, the social impact of gambling on the local community, and the impact of problem gambling. The consultants stated that the major research methods they would use would be historical data, telephone surveys of local residents, telephone interviews with key personnel, and use of an economic impact model. In conducting the study, the consultants indicated they would examine four study areas within Iowa. Study area I would be all of Iowa, area II would be that area in Iowa within a 50-mile radius of a casino, area III would be counties with a casino, and area IV would be based upon casino employee zip codes. The consultants briefed the Committee on the data collected so far and described current challenges in obtaining data on all casino visitors and from obtaining information from several convention and visitor bureaus and chambers of commerce.

Governança das áreas marinhas protegidas da província biogeográfica da Macaronésia

As áreas marinhas protegidas (AMPs), enquanto instrumentos de conservação da natureza, contribuem para a conservação, preservação e gestão dos ecossistemas costeiros e marinhos a nível mundial. Na Província Biogeográfica da Macaronésia, as AMPs existentes desempenham este papel de forma preponderante, principalmente no que diz respeito às espécies com impacte económico local. A governança consiste nas interacções entre estruturas, processos e tradições, as quais determinam como são exercidas as responsabilidades, como as decisões são tomadas e como é que a opinião dos cidadãos e grupos de interesse (stakeholders) é integrada no processo de decisão. Assim, a governança das AMPs é um factor determinante para o seu sucesso. Foi estudada a governança das AMPs na Província Biogeográfica da Macaronésia (arquipélagos dos Açores, Madeira, Canárias e Cabo Verde), com a finalidade de verificar se o actual estado de estabelecimento e gestão de AMPs nos quatro arquipélagos é ou não favorável a uma governança conjunta do meio marinho nesta província biogeográfica, tendo em vista os objectivos de conservação da natureza à escala global. Foi desenvolvida uma metodologia própria baseada na análise do quadro legal nacional e internacional e das estruturas governativas das AMPs, e ainda em entrevistas no arquipélago com menor disponibilidade de informação (Cabo Verde). Conclui-se que os três países que fazem parte da área de estudo detêm os quadros legais (internacional, regional e nacional) e institucional considerados suficientes para a conservação dos ecossistemas costeiros e marinhos. Esta análise permitiu a definição de acções que poderão ser desenvolvidas pelos quatro arquipélagos, visando uma gestão conjunta integrada das AMPs na área de estudo. Apesar de existirem vários diplomas e regulamentos jurídicos a nível nacional/regional sobre a conservação marinha, há ainda um longo caminho a percorrer no que diz respeito aos planos de gestão destinados a promover uma abordagem integrada da conservação à escala biogeográfica

Novas Pragas Agrícolas na Ilha de São Nicolau - Cabo Verde - Tuta absoluta (Meyrick) (Lep - Gelechiidae) e Bactrocera invadens (Drew, Tsuruta & White) (Dipt - Tephritidae)

Em algumas das ilhas do Arquipélago de Cabo Verde entraram, nos últimos dois anos, espécies invasoras que constituem pragas de culturas agrícolas e que têm apresentado elevada repercussão económica. Entre elas contam-se a traça do tomateiro, Tuta absoluta (Meyrick) (Lepidoptera: Gelechidae) e Bactrocera invadens (Drew, Tsuruta & White) (Diptera: Tephritidae). Com o objectivo de avaliar a presença destas pragas na ilha de São Nicolau, foram instaladas armadilhas com atractivos em quatro zonas com bananeiras (Ribeira Prata, Fajã, Maiama e Campo de Preguiça) para a monitorização da mosca da fruta. Foram também instaladas ensaios em seis parcelas de tomateiro para a comparação de estratégias de protecção contra T. absoluta, armadilha com feromona sexual para captura em massa em conjunto com Bacillus thuringiensis e tratamento com deltametrina. Das quatro zonas monitorizadas, B. invadens só foi encontrada no Vale da Fajã. No que diz respeito a T. absoluta, fez-se a comparação entre a população presente em três estratos do tomateiro e não se encontraram diferenças significativas. As estratégias de protecção contra T. absoluta também não diferiram significativamente no que se refere ao número de minas nas folhas e frutos furados. Nesidiocoris tenuis foi identificado como inimigo natural de T. absoluta presente na ilha.

Fighting against Malaria: Prevent wars while waiting for the "miraculous" vaccine

The World Health Organization estimates that 300 million clinical cases of malaria occur annually and observed that during the 80's and part of the 90's its incidence increased. In this paper we explore the influence of refugees from civil wars on the incidence of malaria in the refugee-receiving countries. Using civil wars as an instrumental variable we show that for each 1,000 refugees there are between 2,000 and 2,700 cases of malaria in the refugee receiving country. On average 13% of the cases of malaria reported by the WHO are caused by forced migration as a consequence of civil wars.

Chirurgie [Surgery].

The evolution of visceral surgery is characterized by defining with ever increasing precision the real role of new techniques. Hernia repair, abdominal compartment syndrome, pancreatic and colorectal cancers, as well as haemorrhoids, confirm this reality. Although laparoscopy has clear indications in hernia repairs, many still prefer open approach. The abdominal compartment syndrome, now better understood thanks to laparoscopy, is increasingly important in intensive care. The role of laparoscopy for pancreatic and colorectal cancers is still limited. The development of minimally invasive techniques has led to a reduced morbidity of surgery for haemorrhoids and better results. The economic impact of new technologies must remain a primary concern.

Tax Credit Evaluation Study: Historic Preservation and Cultural and Entertainment District Tax Credit, March 2009

During the 2005 Legislative Session the Iowa Department of Revenue received an appropriation to establish the Tax Credits Tracking and Analysis Program (TCTAP) to track tax credit awards and claims. In addition, the Department was directed to perform periodic evaluations of tax credit programs. The purpose of these studies is three-fold: (1) To provide a comparison of the Iowa tax credit program to similar federal and other states’ programs (2) To summarize information related to the usage of the Iowa tax credit (3) To evaluate the economic impact of the tax credit program.

Tax Credit Evaluation Study: Iowa’s Earned Income Tax Credit, February 23007

During the 2005 Legislative Session the Iowa Department of Revenue received an appropriation to establish the Tax Credits Tracking and Analysis Program (TCTAP) to track tax credit awards and claims. In addition, the Department was directed to perform periodic evaluations of tax credit programs. The purpose of these studies is three-fold: (1) To provide a comparison of the Iowa tax credit program to similar federal and other states’ programs (2) To summarize information related to the usage of the Iowa tax credit (3) To evaluate the economic impact of the tax credit program.

Tax Credit Evaluation Study: Iowa’s Biofuel Retailers’ Tax Credits, February 2009

During the 2005 Legislative Session the Iowa Department of Revenue received an appropriation to establish the Tax Credits Tracking and Analysis Program (TCTAP) to track tax credit awards and claims. In addition, the Department was directed to perform periodic evaluations of tax credit programs. The purpose of these studies is three-fold: (1) To provide a comparison of the Iowa tax credit program to similar federal and other states’ programs (2) To summarize information related to the usage of the Iowa tax credit (3) To evaluate the economic impact of the tax credit program.

Tax Credit Evaluation Study: Tax Incentive Programs Used by Biofuel Producers, March 2009

During the 2005 Legislative Session the Iowa Department of Revenue received an appropriation to establish the Tax Credits Tracking and Analysis Program (TCTAP) to track tax credit awards and claims. In addition, the Department was directed to perform periodic evaluations of tax credit programs. The purpose of these studies is three-fold: (1) To provide a comparison of the Iowa tax credit program to similar federal and other states’ programs (2) To summarize information related to the usage of the Iowa tax credit (3) To evaluate the economic impact of the tax credit program.