Le silence comme outil thérapeutique dans la dépression : élaboration théorique basée sur une étude de cas

À l'aide d'un exemple clinique, nous élaborons les différentes fonctions que peut avoir le silence dans les thérapies cognitives et comportementales de la dépression. Les silences d'une patiente déprimée, suivie en psychothérapie, sont documentés et analysés. Le silence peut, chez la même personne, tantôt produire un apaisement ou organiser la pensée, donc s'avérer productif, tantôt représenter une tentative d'échapper à du matériel douloureux, donc s'avérer peu productif. Ainsi, le thérapeute aura fondamentalement le choix, soit de respecter ces silences soit de les rompre et de parler. Pour l'aider dans ce choix, nous repérons différentes catégories de silences et les mettons en lien avec la littérature à ce sujet, afin d'introduire le silence comme outil thérapeutique à part entière dans le traitement cognitivo-comportemental de la dépression. © 2013 Association fran4aise de thérapie comportementale et cognitive. Publié par Elsevier Masson SAS. Tous droits réservés.

Comparative genomics suggests that the human pathogenic fungus Pneumocystis jirovecii acquired obligate biotrophy through gene loss.

Pneumocystis jirovecii is a fungal parasite that colonizes specifically humans and turns into an opportunistic pathogen in immunodeficient individuals. The fungus is able to reproduce extracellularly in host lungs without eliciting massive cellular death. The molecular mechanisms that govern this process are poorly understood, in part because of the lack of an in vitro culture system for Pneumocystis spp. In this study, we explored the origin and evolution of the putative biotrophy of P. jirovecii through comparative genomics and reconstruction of ancestral gene repertoires. We used the maximum parsimony method and genomes of related fungi of the Taphrinomycotina subphylum. Our results suggest that the last common ancestor of Pneumocystis spp. lost 2,324 genes in relation to the acquisition of obligate biotrophy. These losses may result from neutral drift and affect the biosyntheses of amino acids and thiamine, the assimilation of inorganic nitrogen and sulfur, and the catabolism of purines. In addition, P. jirovecii shows a reduced panel of lytic proteases and has lost the RNA interference machinery, which might contribute to its genome plasticity. Together with other characteristics, that is, a sex life cycle within the host, the absence of massive destruction of host cells, difficult culturing, and the lack of virulence factors, these gene losses constitute a unique combination of characteristics which are hallmarks of both obligate biotrophs and animal parasites. These findings suggest that Pneumocystis spp. should be considered as the first described obligate biotrophs of animals, whose evolution has been marked by gene losses.

Improving cardiovascular and renal outcomes in gout: what should we target?

Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.

LiveCount Assay: concomitant measurement of cytolytic activity and phenotypic characterisation of CD8(+) T-cells by flow cytometry.

Tumour immunologists strive to develop efficient tumour vaccination and adoptive transfer therapies that enlarge the pool of tumour-specific and -reactive effector T-cells in vivo. To assess the efficiency of the various strategies, ex vivo assays are needed for the longitudinal monitoring of the patient's specific immune responses providing both quantitative and qualitative data. In particular, since tumour cell cytolysis is the end goal of tumour immunotherapy, routine immune monitoring protocols need to include a read-out for the cytolytic efficiency of Ag-specific cells. We propose to combine current immune monitoring techniques in a highly sensitive and reproducible multi-parametric flow cytometry based cytotoxicity assay that has been optimised to require low numbers of Ag-specific T-cells. The possibility of re-analysing those T-cells that have undergone lytic activity is illustrated by the concomitant detection of CD107a upregulation on the surface of degranulated T-cells. To date, the LiveCount Assay provides the only possibility of assessing the ex vivo cytolytic activity of low-frequency Ag-specific cytotoxic T-lymphocytes from patient material.

Who wrote the Second Ave maris stella of Tomás Luis de Victoria?

Contrary to what Felipe Pedrell indicates, the second Ave maris stella in his Victoria's collected works (vol. V, 1908, pp. 100-3, n° 33) doesn't appear in the collection published in 1600 in Madrid by the composer, nor in any other of the musician's books. In the 1600 edition, Victoria reissues the two first verses (plainchant followed by polyphony) of the Ave maris stella published in 1576 and then again in 1581. The earliest source of the problematic Ave maris stella is Munich, Bayerische Staatsbibliothek, Musik-Abteilung, 2 Mus. pr. 23 handschriftlicher Beiband, dating from the third quarter oft he seventeenth century. This source is a manuscrit that runs as an appendix to the 1581 edition of Victoria's hymns. No attributions are given in the manuscript. The first attributions of the piece to Victoria arise in the nineteenth century, in manuscripts copied by Johann Michael Hauber, Johann Caspar Aiblinger, August Baumgartner and Carl Proske, and preserved in Munich and Regensburg. Proske pubished the piece in his Musica divina in 1859 (Annus primus, vol. III, pp. 419-24). The most probable hypothesis ist that Pedrell had knowledge of the second Ave maris stella, under the spanish composer's name, via Proske's Musica divina. In all likelihood the piece is not by Victoria, not least because the composer has never written odd polyphonic verses of hymns. In his Studies in the Music of Tomás Luis de Victoria (2001), Eugene Casjen Cramer relies on the supposed authenticity of the work to ascribe the others pieces of Munich, Bayerische Staatsbibliothek, Musik-Abteilung, 2 Mus. pr. 23 handschriftlicher Beiband to the composer. These attributions should therefore be refuted.

Evolutionary insights on C4 photosynthetic subtypes in grasses from genomics and phylogenetics

In plants, an oligogene family encodes NADP-malic enzymes (NADP-me), which are responsible for various functions and exhibit different kinetics and expression patterns. In particular, a chloroplast isoform of NADP-me plays a key role in one of the three biochemical subtypes of C4 photosynthesis, an adaptation to warm environments that evolved several times independently during angiosperm diversification. By combining genomic and phylogenetic approaches, this study aimed at identifying the molecular mechanisms linked to the recurrent evolutions of C4-specific NADP-me in grasses (Poaceae). Genes encoding NADP-me (nadpme) were retrieved from genomes of model grasses and isolated from a large sample of C3 and C4 grasses. Genomic and phylogenetic analyses showed that 1) the grass nadpme gene family is composed of four main lineages, one of which is expressed in plastids (nadpme-IV), 2) C4-specific NADP-me evolved at least five times independently from nadpme-IV, and 3) some codons driven by positive selection underwent parallel changes during the multiple C4 origins. The C4 NADP-me being expressed in chloroplasts probably constrained its recurrent evolutions from the only plastid nadpme lineage and this common starting point limited the number of evolutionary paths toward a C4 optimized enzyme, resulting in genetic convergence. In light of the history of nadpme genes, an evolutionary scenario of the C4 phenotype using NADP-me is discussed.

Dextramers: new generation of fluorescent MHC class I/peptide multimers for visualization of antigen-specific CD8+ T cells.

Direct identification as well as isolation of antigen-specific T cells became possible since the development of "tetramers" based on avidin-fluorochrome conjugates associated with mono-biotinylated class I MHC-peptide monomeric complexes. In principle, a series of distinct class I MHC-peptide tetramers, each labelled with a different fluorochrome, would allow to simultaneously enumerate as many unique antigen-specific CD8(+) T cells. Practically, however, only phycoerythrin and allophycocyanin conjugated tetramers have been generally available, imposing serious constraints for multiple labeling. To overcome this limitation, we have developed dextramers which are multimers based on a dextran backbone bearing multiple fluorescein and streptavidin moieties. Here we demonstrate the functionality and optimization of these new probes on human CD8(+) T cell clones with four independent antigen specificities. Their applications to the analysis of relatively low frequency antigen-specific T cells in peripheral blood, as well as their use in fluorescence microscopy, are demonstrated. The data show that dextramers produce a stronger signal than their fluoresceinated tetramer counterparts. Thus, these could become the reagents of choice as the antigen-specific T cell labeling transitions from basic research to clinical application.

MGMT testing-the challenges for biomarker-based glioma treatment.

Many patients with malignant gliomas do not respond to alkylating agent chemotherapy. Alkylator resistance of glioma cells is mainly mediated by the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). Epigenetic silencing of the MGMT gene by promoter methylation in glioma cells compromises this DNA repair mechanism and increases chemosensitivity. MGMT promoter methylation is, therefore, a strong prognostic biomarker in paediatric and adult patients with glioblastoma treated with temozolomide. Notably, elderly patients (>65-70 years) with glioblastoma whose tumours lack MGMT promoter methylation derive minimal benefit from such chemotherapy. Thus, MGMT promoter methylation status has become a frequently requested laboratory test in neuro-oncology. This Review presents current data on the prognostic and predictive relevance of MGMT testing, discusses clinical trials that have used MGMT status to select participants, evaluates known issues concerning the molecular testing procedure, and addresses the necessity for molecular-context-dependent interpretation of MGMT test results. Whether MGMT promoter methylation testing should be offered to all individuals with glioblastoma, or only to elderly patients and those in clinical trials, is also discussed. Justifications for withholding alkylating agent chemotherapy in patients with MGMT-unmethylated glioblastomas outside clinical trials, and the potential role for MGMT testing in other gliomas, are also discussed.

Jean-Baptiste Perronneau (ca. 1715-1783). Un portraitiste dans l'Europe des Lumières

Les monographies consacrées à Jean-Baptiste Perronneau (ca 1715-1783) à la fin du XIXe siècle et au début du XXe siècle traduisaient l'engouement pour l'art du XVIIIesiècle qui se déployait dans le Tout Paris de la Belle Époque. Elles rendaient justice au peintre de l'Académie royale de peinture et de sculpture de Paris, et à l'un des peintres favoris des contemporains des Impressionnistes qu'elles présentaient comme un artiste éclipsé de son vivant par son prestigieux aîné, Maurice Quentin Delatour (1704-1788). La première partie de la thèse étudie la carrière parisienne du peintre, ses appuis artistiques et sociaux, ses pratiques au pastel et à l'huile, de l'agrément en 1746 à la réception en 1753 et avant le début de la période des voyages en 1756. La rivalité avec Delatour, mise en scène dans un esprit d'émulation au Salon du Louvre pendant plus de vingt ans, y est largement évoquée. Un même nombre de portraits exposés fait comprendre que Perronneau avait de son vivant la faveur des artistes et du public. Il permet de mesurer les effets de la rivalité avec le peintre de Cour sur sa carrière. Delatour faisait exposer en 1750 son autoportrait à côté de son portrait demandé à Perronneau. Les qualités des deux peintres étaient comparées par la nouvelle critique. Notre étude s'attache à ce qui les rapproche comme à ce qui les sépare. Dans la deuxième partie, les peintres des milieux artistiques qu'il fréquente, Louis Tocqué, Jean-Baptiste Oudry, Charles Nicolas Cochin, pour citer les principaux, sont convoqués pour évaluer l'art de Perronneau dans ce que Cochin appelle la « ressemblance savante ». Les peintres les plus ambitieux s'attachent à son interprétation malgré les difficultés dues aux réactions de leur clientèle. La façon dont procède Perronneau est ici envisagée suivant deux aspects : d'une part, la composition du portrait selon une idée du naturel qui détermine l'attitude et une certaine imitation des défauts ; d'autre part, l'imitation de la nature qui réside dans les qualités de l'art, et donc picturales, appréciées des amateurs avertis. La façon qui lui est propre est de composer un naturel selon des poses variées, fondé sur la noblesse de l'attitude conjuguée à la simplicité, conformément à l'idéal courtois en vigueur depuis le XVIe siècle ; elle reste immuable au long de sa carrière. Dans l'imitation de la nature, sont mis en évidence des aspects cachés du faire lors de la mise en place du relief de la figure, les références aux maîtres anciens, Rembrandt, Van Dyck, la conscience de la distance à laquelle le tableau doit être vu, qui atténue la vigueur de la touche, comme le fait le verre qui sert aussi de vernis au pastel. L'idée de sprezzatura qui régit la distinction légère de la pose se décèle à la surface de ses portraits à travers l'apparence de facilité qu'il s'attache à leur donner, et jusque dans l'inimitable retouche finale. Grâce à la qualité de sa retouche, Perronneau accroît sensiblement dans certaines oeuvres à partir de 1768 l'expression savante et inventive de son sentiment. Afin de peindre comme il l'entend tout en gagnant sa vie et celle de sa famille, le peintre prend le parti de voyager comme l'y autorisait la libéralité de son statut. Dans la troisième partie est étudiée la trame de ses voyages que constituent les recommandations dont il bénéficie. Les identités des quatre cent dix modèles peints en France et en Europe de 1740 à 1782 sont systématiquement étudiées dans le catalogue ainsi que les conditions de leur rencontre avec le peintre. Elles décrivent une clientèle variée représentative de la mobilité des statuts dans l'Europe d'ancien Régime dont la composante nouvelle est la clientèle du monde de la banque internationale et du grand commerce. Leurs portraits peints à l'étranger ou dans les villes de Province que Perronneau présente au Salon irritent et inquiètent l'élite parisienne et donne lieu à de nouvelles tensions avec l'éternel rival, Delatour, au Salon de 1767. Perronneau se sent à juste titre évincé de Paris. Alors que l'on avait pu penser qu'il avait peu souffert des critiques du philosophe qui ne furent publiées qu'après sa mort, il apparaît que sa réputation pâtit de ses jugements diffusés par les nouvelles à la main au-delà des frontières et jusqu'auprès de la prestigieuse clientèle qui lui était acquise. Le travail sur son la carrière et l'oeuvre de Perronneau permet surtout une compréhension nouvelle de l'art du portrait au milieu du siècle, au moment où la représentation individuelle n'a jamais encore touché un aussi large public et où l'Académie ambitionne d'élever cet art au plus haut degré.

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications.

Transitoriness in cancer patients: a cross-sectional survey of lung and gastrointestinal cancer patients.

Despite earlier diagnosis and advancements in treatment, cancer remains a leading cause of death in the world (13% of all deaths according to the World Health Organization) among men and women. Cancer accounts for approximately 20% of the deaths in the USA every year. Here, we report the findings from a cross-sectional survey of psychosocial factors in lung and gastrointestinal cancer patients. The aim of the study was to explore the associations among transitoriness, uncertainty, and locus of control (LOC) with quality of life. Transitoriness is defined as a person's confrontation with life's finitude due to a cancer diagnosis. A total of 126 patients with lung or gastrointestinal cancer completed eight self-reporting questionnaires addressing demographics, spiritual perspective, symptom burden, transitoriness, uncertainty, LOC, and quality of life. Transitoriness, uncertainty, and LOC were significantly associated with one another (r = 0.3267, p = 0.0002/r = 0.1994, p = 0.0252, respectively). LOC/belief in chance has a significant inverse relationship with patients' quality of life (r = -0.2505, p = 0.0047). Transitoriness, uncertainty, and LOC were found to have a significant inverse relationship with patients' quality of life (transitoriness state: r = -0.5363, p = 0.0000/trait: r = -0.4629, p = 0.0000/uncertainty: r = -0.4929, p = 0.0000/internal LOC: r = 0.1759, p = 0.0489/chance LOC: r = -0.2505, p = 0.0047). Transitoriness, uncertainty, and LOC are important concepts as they adversely influence patients' quality of life. Incorporating this finding into the care of cancer patients may provide them with the support they need to cope with treatment and maintenance of a positive quality of life.

Therapeutic concepts in adult and paediatric eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) was first described in the early 1990s. Although initially reported to be a rare entity, EoE has rapidly become a regularly diagnosed disease with a prevalence of approximately 1 in 2,000 individuals in the USA and Europe. The disease is characterized by a combination of oesophageal dysfunction and predominant eosinophilic infiltration of the oesophageal tissue. At diagnosis, other diseases that can be associated with oesophageal eosinophilic infiltration must be ruled out. Children with EoE present with a wide variety of symptoms, whereas adults mostly present with dysphagia for solid food and chest pain. Histologic features of EoE resemble those of T-helper type 2 inflammation. Endoscopy should be carried out to establish the diagnosis, but endoscopic abnormalities are not pathognomonic for EoE and the examination might not show histologic abnormality. Treatment modalities for EoE include drugs (corticosteroids, PPIs, antiallergic and biologic agents), hypoallergenic diets and oesophageal dilatation for strictures that are unresponsive to medical therapy. Unresolved eosinophilic inflammation leads to the formation of oesophageal strictures, which probably increase the risk of food bolus impactions. To date, long-term strategies for the therapeutic management of this chronic inflammatory disease remain poorly defined.