Traitement de l'ischémie critique chronique des membres inférieurs en 2014 [Treatment of critical lower limb ischemia].

Critical limb ischemia is a major public health problem in our western countries due to the epidemia of (diabesity). The outcome of patients suffering from critical limb ischemia reains poor with an amputation free survival rate at one year of about 50%. The treatment should be multidiciplinary and done in emergency in specialized centers to ensure the limb salvage: this management should be centered aroud 3 axis: the screening of the cardiovascular risk factors, the best medical treatment and the invasive approaches. Due to multiple endovascular technical innovations, more frail patients with com plex diseases can be treated with good results. Therefore, the endovascular treatment is essential in the management of such patients by vascular surgeons.

Chimpanzees and supporting models in the study of malaria pre-erythrocytic stages

Chimpanzees are being used in the study of immune response to Plasmodium falciparum malaria pre-erythrocytic stages (MPES). Responses induced by immunisation with recombinant/synthetic antigens and by irradiated sporozoites are being evaluated in a model system that is phylogenetically close to humans and that is amenable to limited manipulation not possible in humans. The value of chimpanzees for the in-depth study of immunological mechanisms at work in MPES-induced protection are discussed. A total number of 7 chimpanzees have been used to evaluate the immune response to recombinant antigens, and 5 have been challenged with large numbers of sporozoites, followed by surgical liver-wedge resection, in order to generate infected liver tissue for histological and immunological studies. As a complementary model, SCID mice carrying live, transplanted human and primate hepatocytes have been inoculated with sporozoites and infection of transplanted cells has been monitored by histological and immunological methods. In ongoing experiments chimpanzees are being immunised with MPES-derived lipopeptides that have been shown to overcome MHC restriction in mice, and with irradiated sporozoites.

A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.

AbstractBACKGROUND: KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences.METHOD: To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression.RESULTS: We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression.

A critical application of securitization theory: overcoming the normative dilemma of writing security

This article addresses the normative dilemma located within the application of `securitization,’ as a method of understanding the social construction of threats and security policies. Securitization as a theoretical and practical undertaking is being increasingly used by scholars and practitioners. This scholarly endeavour wishes to provide those wishing to engage with securitization with an alternative application of this theory; one which is sensitive to and self-reflective of the possible normative consequences of its employment. This article argues that discussing and analyzing securitization processes have normative implications, which is understood here to be the negative securitization of a referent. The negative securitization of a referent is asserted to be carried out through the unchallenged analysis of securitization processes which have emerged through relations of exclusion and power. It then offers a critical understanding and application of securitization studies as a way of overcoming the identified normative dilemma. First, it examines how the Copenhagen School’s formation of securitization theory gives rise to a normative dilemma, which is situated in the performative and symbolic power of security as a political invocation and theoretical concept. Second, it evaluates previous attempts to overcome the normative dilemma of securitization studies, outlining the obstacles that each individual proposal faces. Third, this article argues that the normative dilemma of applying securitization can be avoided by firstly, deconstructing the institutional power of security actors and dominant security subjectivities and secondly, by addressing countering or alternative approaches to security and incorporating different security subjectivities. Examples of the securitization of international terrorism and immigration are prominent throughout.

Activity of 9-acridanone-hydrazone drugs detected at the pre-postural phase, in the experimental schistosomiasis mansoni

The compound Ro-15.5458/000, derivative in the class of 9-acridanone-hydrazones, was found to be effective against Schistosoma mansoni in mice, killing almost all the skin schistosomules (24 hr after infection), when administered at the dose of 100 mg/kg. In experiments carried out with Cebus monkeys, the drug was shown to be fully effective at 25 mg/kg, 7 days after infection. These data, associated with the good results obtained earlier at the post-postural phase of schistosomiasis, allow the inference that this promising compound may be important in the set of antischistosomal drugs, depending on further toxicological and clinical tests.

Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies.

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

Possibilitats i límits de la democràcia deliberativa

La meva investigació s’articula entorn a l’obra del filòsof alemany Jürgen Habermas. L’aportació filosòfica més important de Habermas ha estat l’elaboració d’una racionalitat discursiva. Aquesta nova manera d’entendre la raó com a discurs ha tingut importants repercussions en l’àmbit de la filosofia i de les ciències socials en general. La primera part de la meva investigació analitza l’obra de Habermas, posant èmfasi en el procés de configuració d’aquesta racionalitat discursiva. Aquest primer període culmina amb la presentació de la tesina “Introducció al pensament i l’obra de Jürgen Habermas”. Com a resultat d’aquesta investigació, la meva recerca es centrarà, primer, en les nocions habermasianes de publicitat (Öffentlichkeit) i d’opinió pública (öffentliche Meinung) i, finalment, en l’anomenada democràcia deliberativa. Per tant, la recerca consta de dos part estretament relacionades: (1) un anàlisi del procés de configuració d’una raó discursiva en l’obra de Habermas; (2) una valoració crítica dels límits i les possibilitats de la democràcia deliberativa en les societats contemporànies. Aquesta darrera fase d’investigació –en la qual treballo actualment– s’endinsa en el debat dels “teòrics deliberatius”. Entre d’altres, aprofundeix en les repercussions ètiques i polítiques d’una relació problemàtica entre esfera pública i esfera privada. Desfer aquesta problemàtica passa per repensar l’exigència d’una racionalitat imparcial que, alhora, sigui Desfer aquesta problemàtica capaç de garantir la participació democràtica de la ciutadania en el context actual, on el pluralisme de valors ha esdevingut un dels fenòmens vertebradors de les societats contemporànies.

A critical role for the T cell receptor alpha-chain connecting peptide domain in positive selection of CD1-independent NKT cells.

Natural killer T (NKT) cells are a subset of mature alpha beta TCR(+) cells that co-express NK lineage markers. Whereas most NKT cells express a canonical Valpha14/Vbeta8.2 TCR and are selected by CD1d, a minority of NKT cells express a diverse TCR repertoire and develop independently of CD1d. Little is known about the selection requirements of CD1d-independent NKT cells. We show here that NKT cells develop in RAG-deficient mice expressing an MHC class II-restricted transgenic TCR (Valpha2/Vbeta8.1) but only under conditions that lead to negative selection of conventional T cells. Moreover development of NKT cells in these mice is absolutely dependent upon an intact TCR alpha-chain connecting peptide domain, which is required for positive selection of conventional T cells via recruitment of the ERK signaling pathway. Collectively our data demonstrate that NKT cells can develop as a result of high avidity TCR/MHC class II interactions and suggest that common signaling pathways are involved in the positive selection of CD1d-independent NKT cells and conventional T cells.

How critical is timing for the diagnosis of influenza in general practice?

Résumé La performance diagnostic des signes et symptômes de la grippe a principalement été étudiée dans le cadre d'études contrôlées avec des critères d'inclusion stricts. Il apparaît nécessaire d'évaluer ces prédicteurs dans le cadre d'une consultation ambulatoire habituelle en tenant compte du délai écoulé entre le début des symptômes et la première consultation ainsi que la situation épidémiologique. Cette étude prospective a été menée à la Policlinique Médicale Universitaire durant l'hiver 1999-2000. Les patients étaient inclus s'ils présentaient un syndrome grippal et si le praticien suspectait une infection à Influenza. Le médecin administrait un questionnaire puis une culture d'un frottis de gorge était réalisée afin de documenter l'infection. 201 patients ont été inclus dans l'étude. 52% avaient une culture positive pour Influenza. En analyse univariée, une température > 37.8° (OR 4.2; 95% CI 2.3-7.7), une durée des symptômes < 48h (OR 3.2; 1.8-5.7), une toux (OR 3.2; 1-10.4) et des myalgies (OR 2.8; 1.0-7.5) étaient associés au diagnostic de grippe. En analyse de régression logistique, le modèle le plus performant qui prédisait la grippe était l'association d'une durée des symptômes <48h, une consultation en début d'épidémie, une température > 37.8° et une toux (sensibilité 79%, spécificité 69%, valeur prédictive positive 67%, une valeur prédictive négative de 73% et aire sous la courbe (ROC) de 0.74). En plus des signes et symptômes prédicteurs de la grippe, le médecin de premier recours devrait prendre en compte dans son jugement la durée des symptômes avant la première consultation et le contexte épidémiologique (début, pic, fin de l'épidémie), car ces deux paramètres modifient considérablement la valeurs des prédicteurs lors de l'évaluation de la probabilité clinique d'un patient d'avoir une infection à Influenza.

Screening for elevated blood pressure in children and adolescents: a critical appraisal.

Although screening for elevated blood pressure (BP) in adults is beneficial, evidence of its beneficial effects in children is not clear. Elevated BP in children is associated with atherosclerosis early in life and tracks across the life course. However, because of the high variability in BP, tracking is weak, and having an elevated BP in childhood has a low predictive value for having elevated BP later in life. The absolute risk of cardiovascular diseases associated with a given level of BP in childhood and the long-term effect of treatment beginning in childhood are not known. No study has experimentally evaluated the benefits and harm of BP screening in children. One modeling study indicates that BP screen-and-treat strategies in adolescents are moderately cost-effective but less cost-effective than population-wide interventions to decrease BP for the reduction of coronary heart diseases. The US National Heart, Lung, and Blood Institute and the European Society of Hypertension recommend that children 3 years of age and older have their BP measured during every health care visit. According to the US Preventive Services Task Force, there is no sufficient evidence to recommend for or against screening, but their recommendations have to be updated. Whether the benefits of universal BP screening in children outweigh the harm has to be determined. Studies are needed to assess the absolute risk of cardiovascular diseases associated with elevated BP in childhood, to evaluate how to simplify the identification of elevated BP, to evaluate the long-term benefits and harm of treatment beginning in childhood, and to compare universal and targeted screening strategies.

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar : Eficàcia dels models d’entrevista forense

Entrevistant infants pre-escolars víctimes d’abús sexual i/o maltractament familiar: eficàcia dels models d’entrevista forense Entrevistar infants en edat preescolar que han viscut una situació traumàtica és una tasca complexa que dins l’avaluació psicològica forense necessita d’un protocol perfectament delimitat, clar i temporalitzat. Per això, s’han seleccionat 3 protocols d’entrevista: el Protocol de Menors (PM) de Bull i Birch, el model del National Institute for Children Development (NICHD) de Michel Lamb, a partir del qual es va desenvolupar l’EASI (Evaluación del Abuso Sexual Infantojuvenil) i l’Entrevista Cognitiva (EC) de Fisher i Geiselman. La hipòtesi de partida vol comprovar si els anteriors models permeten obtenir volums informatius diferents en infants preescolars. Conseqüentment, els objectius han estat determinar quin dels models d’entrevista permet obtenir un volum informatiu amb més precisions i menys errors, dissenyar un model d’entrevista propi i consensuar aquest model. En el treball s’afegeixen esquemes pràctics que facilitin l’obertura, desenvolupament i tancament de l’entrevista forense. La metodologia ha reproduït el binomi infant - esdeveniment traumàtic, mitjançant la visualització i l’explicació d’un fet emocionalment significatiu amb facilitat per identificar-se: l’accident en bicicleta d’un infant que cau, es fa mal, sagna i el seu pare el cura. A partir d’aquí, hem entrevistat 135 infants de P3, P4 i P5, mitjançant els 3 models d’entrevista referits, enfrontant-los a una demanda específica: recordar i narrar aquest esdeveniment. S’ha conclòs que el nivell de record correcte, quan s’utilitza un model d’entrevista adequat amb els infants en edat preescolar, oscil•la entre el 70-90%, fet que permet defensar la confiança en els records dels infants. Es constata que el percentatge d’emissions incorrectes dels infants en edat preescolar és mínim, al voltant d’un 5-6%. L’estudi remarca la necessitat d’establir perfectament les regles de l’entrevista i, per últim, en destaca la ineficàcia de les tècniques de memòria de l’entrevista cognitiva en els infants de P3 i P4. En els de P5 es comencen a veure beneficis gràcies a la tècnica de la reinstauració contextual (RC), estant les altres tècniques fora de la comprensió i utilització dels infants d’aquestes edats. Interviewing preschoolers victims of sexual abuse and/or domestic abuse: Effectiveness of forensic interviews models 135 preschool children were interviewed with 3 different interview models in order to remember a significant emotional event. Authors conclude that the correct recall of children ranging from 70-90% and the percentage of error messages is 5-6%. It is necessary to fully establish the rules of the interview. The present research highlights the effectiveness of the cognitive interview techniques in children from P3 and P4. Entrevistando niños preescolares víctimas de abuso sexual y/o maltrato familiar: eficacia de los modelos de entrevista forense Se han entrevistado 135 niños preescolares con 3 modelos de entrevista diferentes para recordar un hecho emocionalmente significativo. Se concluye que el recuerdo correcto de los niños oscila entre el 70-90% y el porcentaje de errores de mensajes es del 5-6%. El estudio remarca la necesidad de establecer perfectamente las reglas de la entrevista y se destaca la ineficacia de las técnicas de la entrevista cognitiva en los niños de P3 y P4.

The nuclear matrix: a critical appraisal.

It is becoming increasingly clear that the cell nucleus is a highly structurized organelle. Because of its tight compartmentalization, it is generally believed that a framework must exist, responsible for maintaining such a spatial organization. Over the last twenty years many investigations have been devoted to identifying the nuclear framework. Structures isolated by different techniques have been obtained in vitro and are variously referred to as nuclear matrix, nucleoskeleton or nuclear scaffold. Many different functions, such as DNA replication and repair, mRNA transcription, processing and transport have been described to occur in close association with these structures. However, there is still much debate as to whether or not any of these preparations corresponds to a nuclear framework that exists in vivo. In this article we summarize the most commonly-used methods for obtaining preparations of nuclear frameworks and we also stress the possible artifacts that can be created in vitro during the isolation procedures. Emphasis is placed also on the protein composition of the frameworks as well as on some possible signalling functions that have been recently described to occur in tight association with the nuclear matrix.