Déterminants métaboliques de la progression de la sténose aortique

La sténose aortique est la maladie cardiovasculaire la plus fréquente dans les pays industrialisés après la maladie coronarienne et l’hypertension artérielle. Malheureusement, il n’existe actuellement aucun traitement médical efficace pour réduire sa progression et ses effets néfastes sur le remodelage et la fonction ventriculaire gauche. Le remplacement valvulaire aortique est le seul traitement efficace de la sténose aortique sévère symptomatique. Afin de développer des approches pharmacologiques efficaces pour réduire la progression de la maladie, il est primordial d’élucider les facteurs et les mécanismes qui sont impliqués dans sa pathogénèse. La sténose aortique, qui se caractérise par un dépôt progressif de calcium au niveau des feuillets et de l’anneau de la valve aortique, a longtemps été considérée comme une maladie dégénérative. Cependant, de récentes études ont suggéré que la sténose aortique était un processus actif vraisemblablement lié à l’athérosclérose. La sténose aortique apparait comme une pathologie complexe faisant intervenir différents processus liés à l’obésité viscérale et au syndrome métabolique, mais aussi à la dérégulation du métabolisme phospho-calcique. De plus, ces processus impliqués au niveau valvulaire peuvent aussi intervenir au niveau de l’aorte et du ventricule gauche. L’évaluation des mécanismes physiopathologiques impliqués à la fois au niveau de la valve, de l’aorte et du ventricule, ainsi que leurs interactions, permettrait de mieux connaitre et comprendre la pathologie valvulaire calcifiante et d’identifier de nouvelles cibles thérapeutiques dans cette population. L’objectif général de mon projet de doctorat est d’identifier et de déterminer l’impact respectif des différents facteurs métaboliques liés à l’obésité viscérale sur la progression de la sténose aortique, et du remodelage et de la dysfonction ventriculaire gauche.Aortic stenosis is the most common cardiovascular disease in developed countries after coronary artery disease and systemic arterial hypertension. Unfortunately, no medical therapies have been proven to decrease either the progression of valve stenosis or the resulting adverse effects on myocardial remodeling or function. Surgical aortic valve replacement is currently the sole option for the treatment of severe symptomatic aortic stenosis. To develop efficient pharmacological approaches to slow the progression of aortic stenosis, it is crucial to elucidate the factors and mechanisms that are involved in the pathogenesis of this disease. Aortic stenosis, which is characterized by a progressive calcium deposition in aortic valve leaflets and annulus, has long been considered as a degenerative disease. However, recent studies have suggested that aortic stenosis was an active process likely related to atherosclerosis. Aortic stenosis appears as a complex disease involving several processes related to visceral obesity and metabolic syndrome, as well as deregulation of the phosphor-calcic metabolism. Furthermore, these processes involved at the valvular level appear to be also implicated at the level of the aorta and the left ventricle. Assessment of the pathophysiological mechanisms involded both at the valve, aorta and ventricle, as well as their interactions, would better know and understand calcific valvular disease and identify new therapeutic targets in this population. The general objective of my PhD project is to identify and determine the respective impact of different metabolic factors related to visceral obesity on the progression of the valve stenosis, as well as left ventricular remodeling and dysfunction

100 anos do primeiro trabalho acadêmico sobre psicanálise no Brasil – a dissertação de Genserico

Este artigo visa tratar do primeiro trabalho acadmico sobre psicanlise no Brasil, tendo como principal objetivo apresentar a forma como Genserico Arago de Souza Pinto se apropriou da psicanlise a partir do debate com interlocutores como Juliano Moreira e Austregsilo Rodrigues de Lima. O destaque ao papel da sexualidade na etiologia das neuroses e tambm na vida normal tornasse um dos principais tema desta dissertao

O princípio da liberdade sindical : uma análise a partir das diretrizes internacionais de proteção ao trabalho

Monografia (graduação)—Universidade de Brasília, Faculdade de Direito, 2013.A presente monografia tem como pretensão analisar o princípio da liberdade sindical, realizando-se o cotejo entre sua aplicação plena – que traduziria a situação ideal – e a sua efetividade na realidade brasileira contemporânea – situação real. Para tanto, utilizou-se como estratégia a pesquisa bibliográfica, perfazendo-se o recorte da evolução histórica da compreensão acerca do que vem a ser liberdade sindical, até a culminação no entendimento mais atual, esposado pela Convenção nº 87 da Organização Internacional do Trabalho – ou, simplesmente, OIT –, a qual trata da liberdade sindical plena. Demonstrou-se a necessidade de atenção ao princípio da progressividade no trato da matéria trabalhista, levando-se em conta as implicações de ordem prática que tal princípio suscita, mormente a impossibilidade de se sustentar o sistema da unicidade sindical nos dias atuais. Foram apontadas formas possíveis de incorporação de um sistema sindical compatível com a Convenção nº 87 da OIT, de forma a efetivar-se o princípio fundamental pertinente trazido pela Declaração de 1998 da referida organização. ______________________________________________________________________________ ABSTRACTThe present work has the intention of analysing the principle of freedom of association, carrying out the comparison between its full enforcement – the ideal situation – and its effectiveness in contemporary Brazilian reality – real situation. For such purposes, bibliographic research was utilized as an strategy, making up the outline of the historical evolution of the understanding over what is called freedom of association, leading to the culmination of its most present understanding, exposed by the Convention nº 87 of ILO – International Labour Organization -, which endorses full freedom of association. It has been shown the need for attention to the principle of progress when handling the labour subject, taking in consideration the implications of practical order the principle evokes, especially the unsustainability of the single union system nowadays. Possible forms of incorporation of an association system compatible with the Convention nº 87 of ILO have been pointed, in order to endorse the pertinent fundamental principle brought by the Declaration of 1998 of the referred organization

Trabalho, sofrimento e as narrativas de alguns psicanalistas

O presente artigo é derivado de uma pesquisa que teve o objetivo de apresentar como psicanalistas de orientação lacaniana escutam e lidam com pacientes que têm algum tipo de queixa relacionada ao mundo do trabalho. Partindo de um olhar da Psicologia Social do Trabalho, a pesquisa teve como pressuposto que o contexto social capitalista e as formas de organização do trabalho podem ter consequências para a saúde mental dos trabalhadores. Foram realizadas entrevistas semiestruturadas com cinco psicanalistas, com foco na narração de experiências no tratamento com pacientes acometidos por algum tipo de sofrimento “mental” relacionado ao trabalho. Observou-se que os entrevistados privilegiaram, nos tratamentos que empreenderam, mais os aspectos das dinâmicas da história familiar do que as dinâmicas do mundo do trabalho, reavivando um antigo debate entre o individual e o coletivo

Trabalho, sofrimento e as narrativas de alguns psicanalistas

O presente artigo derivado de uma pesquisa que teve o objetivo de apresentar como psicanalistas de orientao lacaniana escutam e lidam com pacientes que tm algum tipo de queixa relacionada ao mundo do trabalho. Partindo de um olhar da Psicologia Social do Trabalho, a pesquisa teve como pressuposto que o contexto social capitalista e as formas de organizao do trabalho podem ter consequncias para a sade mental dos trabalhadores. Foram realizadas entrevistas semiestruturadas com cinco psicanalistas, com foco na narrao de experincias no tratamento com pacientes acometidos por algum tipo de sofrimento mental relacionado ao trabalho. Observou-se que os entrevistados privilegiaram, nos tratamentos que empreenderam, mais os aspectos das dinmicas da histria familiar do que as dinmicas do mundo do trabalho, reavivando um antigo debate entre o individual e o coletivo

Reflexões sobre a área de pesquisa Filosofia da Psicanálise: um depoimento sobre sua constituição em São Paulo

Este artigo visa contribuir para uma reflexo sobre o dilogo entre Filosofia e Psicanlise a partir dos anos 1970 no que se refere apropriao realizada por intelectuais brasileiros, em especial no cenrio paulista. Acontecimentos significativos como a dissertao de Mezan, a tese de Monzani e o papel poltico e intelectual de Bento Prado Jr., entre outros, marcaram de maneira indelvel a forma como se estabeleceu o dilogo entre Filosofia e Psicanlise no Brasil. a partir dessas peculiaridades que se pode refletir sobre a construo e desenvolvimento de um campo de pesquisa chamado Filosofia da Psicanlise como uma contribuio brasileira

The cell organization underlying structural colour is involved in Flavobacterium IR1 predation.

Flavobacterium IR1 is a gliding bacterium with a high degree of colonial organization as a 2D photonic crystal, resulting in vivid structural coloration when illuminated. Enterobacter cloacae B12, an unrelated bacterium, was isolated from the brown macroalga Fucus vesiculosus from the same location as IR1. IR1 was found to be a predator of B12. A process of surrounding, infiltration, undercutting and killing of B12 supported improved growth of IR1. A combination of motility and capillarity facilitated the engulfment of B12 colonies by IR1. Predation was independent of illumination. Mutants of IR1 that formed photonic crystals less effectively than the wild type were reduced in predation. Conversely, formation of a photonic crystal was not advantageous in resisting predation by Rhodococcus spp. PIR4. These observations suggest that the organization required to create structural colour has a biological function (facilitating predation) but one that is not directly related to the photonic properties of the colony. This work is the first experimental evidence supporting a role for this widespread type of cell organization in the Flavobacteriia

Non-invasive determination of left ventricular workload in patients with aortic stenosis using magnetic resonance imaging and Doppler echocardiographye

Early detection and accurate estimation of aortic stenosis (AS) severity are the most important predictors of successful longterm outcomes in patients. Current clinical parameters used for evaluation of the AS severity have several limitations including flow dependency. Estimation of AS severity is specifically challenging in patients with low-flow and low transvalvular pressure gradient conditions. A proper diagnosis in these patients needs a comprehensive evaluation of the left ventricle (LV) hemodynamic loads. This study has two objectives: (1) developing a lumped-parameter model to describe the ventricular-valvular-arterial interaction and to estimate the LV stroke work (SW); (2) introducing and validating a new index, the normalized stroke work (N-SW), to assess the global hemodynamic load imposed on the LV. N-SW represents the global hemodynamic load that the LV faces for each unit volume of blood ejected. The model uses a limited number of parameters which all can be measured non-invasively using current clinical imaging modalities. The model was first validated by comparing its calculated flow waveforms with the ones measured using Cardiovascular Magnetic Resonance (CMR) in 49 patients and 8 controls. A very good correlation and concordance were found throughout the cycle (median root mean square: 12.21 mL/s) and between the peak values (r = 0.98; SEE = 0.001, p,0.001). The model was then used to determine SW using the parameters measured with transthoracic Doppler-echocardiography (TTE) and CMR. N-SW showed very good correlations with a previously-validated index of global hemodynamic load, the valvular arterial impedance (ZVA), using data from both imaging modalities (TTE: r = 0.82, SEE = 0.01, p,0.001; CMR: r = 0.74, SEE = 0.01, p,0.001). Furthermore, unlike , N-SW was almost independent from variations in the flow rate. This study suggests that considering N-SW may provide incremental diagnostic and prognostic information, beyond what standard indices of stenosis severity and provide, particularly in patients with low LV outflow

Impact of classic and paradoxical low flow on survival after aortic valve replacement for severe aortic stenosis

BackgroundLow flow (LF) can occur with reduced (classic) or preserved (paradoxical) left ventricular ejection fraction (LVEF). ObjectivesThe objective of this study was to compare outcomes of patients with low ejection fraction (LEF), paradoxical low flow (PLF), and normal flow (NF) after aortic valve replacement (AVR). MethodsWe examined 1,154 patients with severe aortic stenosis (AS) who underwent AVR with or without coronary artery bypass grafting. ResultsAmong these patients, 206 (18%) had LEF as defined by LVEF of 35 ml · m2. Aortic valve area was lower in low flow/LVEF groups (LEF: 0.71 ± 0.20 cm2 and PLF: 0.65 ± 0.23 cm2 vs. NF: 0.77 ± 0.18 cm2; p < 0.001). The 30-day mortality was higher (p < 0.001) in LEF and PLF groups than in the NF group (6.3% and 6.3% vs. 1.8%, respectively). SVi and PLF group were independent predictors of operative mortality (odds ratio [OR]: 1.18, p < 0.05; and OR: 2.97, p = 0.004; respectively). At 5 years after AVR, overall survival was 72 ± 4% in LEF group, 81 ± 2% in PLF group, and 85 ± 2% in NF group (p < 0.0001). ConclusionsPatients with LEF or PLF AS have a higher operative risk, but pre-operative risk score accounted only for LEF and lower LVEF. Patients with LEF had the worst survival outcome, whereas patients with PLF and normal flow had similar survival rates after AVR. As a major predictor of perioperative mortality, SVi should be integrated in AS patients’ pre-operative evaluation

FPGA implementation of a 32x32 autocorrelator array for analysis of fast image series

With the evolving technology in CMOS integration, new classes of 2D-imaging detectors have recently become available. In particular, single photon avalanche diode (SPAD) arrays allow detection of single photons at high acquisition rates (\geq 100 kfps), which is about two orders of magnitude higher than with currently available cameras. Here we demonstrate the use of a SPAD array for imaging fluorescence correlation spectroscopy (imFCS), a tool to create 2D maps of the dynamics of fluorescent molecules inside living cells. Time-dependent fluorescence fluctuations, due to fluorophores entering and leaving the observed pixels, are evaluated by means of autocorrelation analysis. The multi-{\tau} correlation algorithm is an appropriate choice, as it does not rely on the full data set to be held in memory. Thus, this algorithm can be efficiently implemented in custom logic. We describe a new implementation for massively parallel multi-{\tau} correlation hardware. Our current implementation can calculate 1024 correlation functions at a resolution of 10{\mu}s in real-time and therefore correlate real-time image streams from high speed single photon cameras with thousands of pixels.Comment: 10 pages, 7 figure