Intérêt D’une Recherche De Thrombophilie Au Cours Des Thromboses De La Veine Porte Dans Un Service De Médecine Interne

Background: Many causes of portal vein thrombosis are described and most patients had a combination of local and systemic risk factors. In many studies, prtothombotic disorders investigations were conducted in various departments of haematologies and/or gastroenterology. In this study, we investigated the systemic risk factors associated or not to abdominal inflammation in a series of patients recruited in a department of Internal Medicine. Methods: We studied, retrospectively from 2005 to 2009, 21 cases of patients with portal vein thrombosis. Patients with cancer are not included in this study. Results: We reported 21 patients with portal vein thrombosis: 8 males (43%) and 13 females (57%). The average age of patients was 46, 6 years (20; 59). Eight (8) patients had abdominal inflammatory pathology and 21 (100%) patients had systemic prothrombotic factors. This etiologic investigation is rentable because in 18 cases, abdominal inflammation and/or prothombotic disorders are diagnosed. This diagnostic, however, can permit to discuss a specific management. Conclusion: Extensive investigation of prothrombotic disorders is necessary in portal vein thrombosis, although if local abdominal inflammation exist

Pattern of DAP12 Expression in Leukocytes from Both Healthy and Systemic Lupus Erythematosus Patients

DAP12 is an ITAM-bearing transmembrane adaptor originally identified on the surface of Natural Killer cells. A broad expression among other immune cells was later found in myeloid and lymphoid cells. However, data on DAP12 expression pattern rely only on immunoblot and microarray analysis. Here, we describe the generation and the characterization of an anti-DAP12 monoclonal antibody. Using this novel reagent, we show that DAP12 expression is restricted to innate immune cells in basal condition. Since a decreased expression of DAP12 has been suggested in NK cells of systemic lupus erythematosus patients, we have further investigated the NK cell receptor repertoire and leukocyte expression of DAP12 in these patients and no major changes were detectable when compared to controls

Uncommon mutational profiles of metastatic colorectal cancer detected during routine genotyping using next generation sequencing

RAS genotyping is mandatory to predict anti-EGFR monoclonal antibodies (mAbs) therapy resistance and BRAF genotyping is a relevant prognosis marker in patients with metastatic colorectal cancer. Although the role of hotspot mutations is well defined, the impact of uncommon mutations is still unknown. In this study, we aimed to discuss the potential utility of detecting uncommon RAS and BRAF mutation profiles with next-generation sequencing. A total of 779 FFPE samples from patients with metastatic colorectal cancer with valid NGS results were screened and 22 uncommon mutational profiles of KRAS, NRAS and BRAF genes were selected. In silico prediction of mutation impact was then assessed by 2 predictive scores and a structural protein modelling. Three samples carry a single KRAS non-hotspot mutation, one a single NRAS non-hotspot mutation, four a single BRAF non-hotspot mutation and fourteen carry several mutations. This in silico study shows that some non-hotspot RAS mutations seem to behave like hotspot mutations and warrant further examination to assess whether they should confer a resistance to anti-EGFR mAbs therapy for patients bearing these non-hotspot RAS mutations. For BRAF gene, non-V600E mutations may characterise a novel subtype of mCRC with better prognosis, potentially implying a modification of therapeutic strategy

Macroautophagy in Dendritic Cells Controls the Homeostasis and Stability of Regulatory T Cells.

Regulatory T cells (Tregs) play a crucial role in controlling autoimmune and inflammatory responses. Recent studies have demonstrated that dendritic cells (DCs) contribute to the homeostasis of peripheral Tregs. Autophagy, a critical pathway for cellular homeostasis, is active in DCs and is upregulated in different inflammatory conditions. We have shown that Tregs are expanded and have phenotypic alterations and impaired suppressive functions in mice with autophagy-deficient DCs. RNA profiling of Tregs revealed that autophagy in DCs is required to stabilize Treg expression signatures. This phenotype is linked to the downregulation of ICOS-Ligand expression in autophagy-deficient DCs, a consequence of the accumulation of ADAM10, the metalloproteinase responsible for its cleavage. Upon inflammation, in antigen-induced arthritis, mice with autophagy-deficient DCs exhibit increased synovial inflammation and cartilage and bone erosion correlating with Treg-to-Th17 conversion. Our data reveal a mechanism that couples autophagy deficiency in DCs to the function, homeostasis, and stability of Tregs

A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque

[EN] Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models. In an initial dose-testing phase we found a Guanfacine dose that increased performance accuracy, decreased distractibility and improved learning. In a second experimental phase using only that dose we examined the faster feature-based reversal learning with Guanfacine with single-subject computational modeling. Parameter estimation suggested that improved learning is not accounted for by varying a single reinforcement learning mechanism, but by changing the set of parameter values to higher learning rates and stronger suppression of non-chosen over chosen feature information. These findings provide an important starting point for developing nonhuman primate models to discern the synaptic mechanisms of attention and learning functions within the context of a computational neuropsychiatry framework.This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Ministry of Economic Development and Innovation (MEDI). We thank Dr. Hongying Wang for invaluable help with drug administration and animal careHassani, SA.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid-Ramírez, JS.; Van Der Meer, MA.; Tiesinga, P.... (2017). 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Expectations and outcome: The role of Proposer features in the Ultimatum Game

Item does not contain fulltextIn social decision-making individuals make choices in an interactive context and their decisions may therefore be influenced by information they receive about features of the other player. These features may 'frame' the other player in particular ways and generate expectations about the outcome. This research examines the impact of information about the Proposer on the Responder's decision in the Ultimatum Game (UG). Two-hundred and forty undergraduates played the UG after being provided with different descriptions of the Proposer's (no information, physical description, psychological description). The results show that acceptance rates are significantly influenced by both offer fairness as well as the type of description. These results support the relevance of the expectation effects due to the framing in social decision making

L'isolement en psychiatrie: point de vue des patients et perspectives éthiques

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Characteristics of Systemic Sclerosis patients with positive anti-Th/To antibodies: About 6 patients and literature review

International audienceAmong the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc.Parmi les anticorps décrits associés à la Sclérodermie Systémique (ScS), les anticorps anti-Th/To (anti-Th/To) sont rares et ont été peu étudiés. Ainsi, nous n’avons que peu de connaissance sur le profil des patients positifs pour les anti-Th/To. À partir d’une Biobanque locale (Marseille, France), nous avons sélectionné de façon rétrospective 6 patients positifs pour les anti-Th/To, en test Immunodot. Tous souffraient de ScS et partageaient des caractéristiques cliniques et biologiques communes, comme la forme cutanée limitée de la ScS, une baisse de la diffusion alvéolocapillaire pulmonaire et un aspect moucheté nucléolaire en immunofluorescence indirecte au test de dépistage des anticorps anti-nucléaires sur cellules Hep-2. Afin de caractériser davantage les patients positifs pour les anti-Th/To, nous avons réalisé une revue de la littérature sur le sujet. À partir de l’étude de 402 patients positifs pour les anti-Th/To, nous confirmons que ces anticorps sont principalement associés à la forme cutanée limitée de la maladie (88 % de l’ensemble des patients), et à une atteinte pulmonaire de la ScS (50 % de l’ensemble des patients). Cette analyse de la littérature illustre la rareté des anti-Th/To avec une fréquence moyenne estimée de 3,4 % chez tous les patients souffrant de ScS dans le monde entier, leur caractère habituellement exclusif vis-à-vis des autres autoanticorps spécifiques de la Sclérodermie, ainsi que leur grande spécificité (environ 98 %) pour le diagnostic de la ScS