Venous cannula performance assessment in a realistic caval tree model.

OBJECTIVES: A new caval tree system was designed for realistic in vitro simulation. The objective of our study was to assess cannula performance for virtually wall-less versus standard percutaneous thin-walled venous cannulas in a setting of venous collapse in case of negative pressure. METHODS: For a collapsible caval model, a very flexible plastic material was selected, and a model with nine afferent veins was designed according to the anatomy of the vena cava. A flow bench was built including a lower reservoir holding the caval tree, built by taking into account the main afferent vessels and their flow provided by a reservoir 6 cm above. A cannula was inserted in this caval tree and connected to a centrifugal pump that, in turn, was connected to a reservoir positioned 83 cm above the second lower reservoir (after-load = 60 mmHg). Using the same pre-load, the simulated venous drainage for cardiopulmonary bypass was realized using a 24 F wall-less cannula (Smartcanula) and 25 F percutaneous cannula (Biomedicus), and stepwise increased augmentation (1500 RPM, 2000 and 2500 RPM) of venous drainage. RESULTS: For the thin wall and the wall-less cannulas, 36 pairs of flow and pressure measurements were realized for three different RPM values. The mean Q-values at 1500, 2000 and 2500 RPM were: 3.98 ± 0.01, 6.27 ± 0.02 and 9.81 ± 0.02 l/min for the wall-less cannula (P <0.0001), versus 2.74 ± 0.02, 3.06 ± 0.05, 6.78 ± 0.02 l/min for the thin-wall cannula (P <0.0001). The corresponding inlet pressure values were: -8.88 ± 0.01, -23.69 ± 0.81 and -70.22 ± 0.18 mmHg for the wall-less cannula (P <0.0001), versus -36.69 ± 1.88, -80.85 ± 1.71 and -101.83 ± 0.45 mmHg for the thin-wall cannula (P <0.0001). The thin-wall cannula showed mean Q-values 37% less and mean P values 26% more when compared with the wall-less cannula (P <0.0001). CONCLUSIONS: Our in vitro water test was able to mimic a negative pressure situation, where the wall-less cannula design performs better compared with the traditional thin-wall cannula.

Toxicokinetics of captan and folpet biomarkers in orally exposed volunteers

The time courses of key biomarkers of exposure to captan and folpet was assessed in accessible biological matrices of orally exposed volunteers. Ten volunteers ingested 1 mg kg(-1) body weight of captan or folpet. Blood samples were withdrawn at fixed time periods over the 72 h following ingestion and complete urine voids were collected over 96 h post-dosing. The tetrahydrophthalimide (THPI) metabolite of captan along with the phthalimide (PI) and phthalic acid metabolites of folpet were then quantified in these samples. Plasma levels of THPI and PI increased progressively after ingestion, reaching peak values ~10 and 6 h post-dosing, respectively; subsequent elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 15.7 and 31.5 h, respectively. In urine, elimination rate time courses of PI and phthalic acid evolved in parallel, with respective t(½) of 27.3 and 27.6 h; relatively faster elimination was found for THPI, with mean t(½) of 11.7 h. However, phthalic acid was present in urine in 1000-fold higher amounts than PI. In the 96 h period post-treatment, on average 25% of folpet dose was excreted in urine as phthalic acid as compared with only 0.02% as PI. The corresponding value for THPI was 3.5%. Overall, THPI and PI appear as interesting biomarkers of recent exposure, with relatively short half-lives; their sensitivity to assess exposure in field studies should be further verified. Although not a metabolite specific to folpet, the concomitant use of phthalic acid as a major biomarker of exposure to folpet should also be considered. Copyright © 2011 John Wiley & Sons, Ltd.

Toll-Interacting Protein Modulates Gut Flora Composition, Epithelial Barrier Integrity and Susceptibility to Colitis

Toll-like receptor ( TLR) s ignals are key to maintaining hostmicrobial i nteractions. T he T oll-interacting-protein (Tollip) is a ubiquitously-expressed inhibitor of inflammasome a nd TLR signaling. W e hypothesized that T ollip might control g ut homeostasis. G enetic ablation of T ollip d id not lead to spontaneous colitis b ut h ad d ramatic c onsequences on t he intestinal expression of the α-defensin cryptidin 4 and the C-type lectin R EGIIIβ. These c hanges were associated with intestinal dysbiosis a nd e nhanced colonization b y segmented filamentous bacteria - a k ey p ro-inflammatory component of the microbiota. Tollip deficiency increased susceptibility to dextran sulfate sodium (DSS) colitis and aggravated chronic Th17-driven colitis in IL-10-/- mice. Flora d epletion w ith a ntibiotics in T ollip-/- mice w as not sufficient to restore DSS colitis susceptibility and deletion of Tollip in n on-hematopoietic c ells using bone-marrow chimeras w as sufficient to increase s usceptibility t o DSS colitis. After D SS administration, we o bserved several e pithelial defects i n Tollip-/- mice including early tight junctions disruption, increased epithelial apoptosis, and increased intestinal permeability. Overall, our data show that T ollip significantly impacts intestinal h omeostasis by controlling b acterial ecology and intestinal r esponse to chemical and immunological stresses.

De l'éclectisme à la pensée d'école en psychothérapie : la voie de l'anthropologie clinique

Ce texte est une prise de position claire face à la pluralité des pratiques psychothérapeutiques : se référant à l'anthropologie clinique, présentée ici selon ses trois visées (pratique, épistémologique et herméneutique), l'auteur rejette les positions extrêmes de l'éclectisme et du dogmatisme liée à la pensée d'école. Chaque thérapeute est invité à se situer dans le champ de la psychothérapie en explicitant sa "philosophie", c'est-à-dire les croyances qui animent ses gestes professionnels.

International Union of Pharmacology. XXXV. The glucagon receptor family.

Peptide hormones within the secretin-glucagon family are expressed in endocrine cells of the pancreas and gastrointestinal epithelium and in specialized neurons in the brain, and subserve multiple biological functions, including regulation of growth, nutrient intake, and transit within the gut, and digestion, energy absorption, and energy assimilation. Glucagon, glucagon-like peptide-1, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, growth hormone-releasing hormone and secretin are structurally related peptides that exert their actions through unique members of a structurally related G protein-coupled receptor class 2 family. This review discusses advances in our understanding of how these peptides exert their biological activities, with a focus on the biological actions and structural features of the cognate receptors. The receptors have been named after their parent and only physiologically relevant ligand, in line with the recommendations of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR).

Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent Fever?

Background: Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever.Methods: PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%).Results: At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak >500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively.Conclusion: While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses

Somatosensory motor bodily representation cortical thinning in Tourette : effects of tic severity, age and gender

Introduction: Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter. Methods: 66 magnetic resonance imaging scans were acquired from 34 TS (age range 10-25, mean 17.19±4.1) and 32 normal controls (NC) (age range 10-20, mean 16.33±3.56). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. Results: We report (1) significant cortical thinning in the fronto-parietal and somatosensory-motor cortices in TS relative to NC (p<0.05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p<0.05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory-motor cortical thickness. Conclusions: TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I.

Infections with intestinal helminths severely impact on human and veterinary health, particularly through the damage that these large parasites inflict when migrating through host tissues. Host immunity often targets the motility of tissue-migrating helminth larvae, which ideally should be mimicked by anti-helminth vaccines. However, the mechanisms of larval trapping are still poorly defined. We have recently reported an important role for Abs in the rapid trapping of tissue-migrating larvae of the murine parasite Heligmosomoides polygyrus bakeri. Trapping was mediated by macrophages (MΦ) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MΦ adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow-derived MΦ, we now identify CD11b as the major complement receptor mediating MΦ adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcγRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcγRI signaling also contributed to the upregulation of MΦ Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcγRI on the MΦ surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MΦ in vitro. Our findings reveal a novel role for IgG2a/c-FcγRI-driven MΦ activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

The sampling of ignitable liquids on suspects' hands

In arson cases, the collection and detection of traces of ignitable liquids on a suspect's hands can provide information to a forensic investigation. Police forces currently lack a simple, robust, efficient and reliable solution to perform this type of swabbing. In this article, we describe a study undertaken to develop a procedure for the collection of ignitable liquid residues on the hands of arson suspects. Sixteen different collection supports were considered and their applicability for the collection of gasoline traces present on hands and their subsequent analysis in a laboratory was evaluated. Background contamination, consisting of volatiles emanating from the collection supports, and collection efficiencies of the different sampling materials were assessed by passive headspace extraction with an activated charcoal strip (DFLEX device) followed by gas chromatography-mass spectrometry (GC-MS) analysis. After statistical treatment of the results, non-powdered latex gloves were retained as the most suitable method of sampling. On the basis of the obtained results, a prototype sampling kit was designed and tested. This kit is made of a three compartment multilayer bag enclosed in a sealed metal can and containing three pairs of non-powdered latex gloves: one to be worn by the sampler, one consisting of a blank sample and the last one to be worn by the person suspected to have been in contact with ignitable liquids. The design of the kit was developed to be efficient in preventing external and cross-contaminations.

Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne® 800 µg/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 ± 27 vs. 11 ± 2 (mean ± SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 ± 21 vs. 14 ± 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability-enhancing effect of PDT.

Parodier l'instrumentalisation de la parole dans les médias : ce que raconter peut dire

Observant la montée de l'instrumentalisation de la narration dans les médias de masse, le présent article vise comprendre les dimensions praxéologiques de l'activité de raconter en communication publique. L'analyse des dimensions praxéologiques permet d'envisager les mouvements discursifs attachés à la narration comme dirigés ou orientés vers un objectif pratique de l'ordre de l'interaction communicative et sociale. Dans le cas présent, il s'agit de saisir les fonctions d'un épisode narratif lors d'un entretien télévisé parodique. Cet entretien, mettant en scène le président français Nicolas Sarkozy interviewé par un journaliste dans le cadre d'un journal télévisé factice, est tiré d'une émission satirique française, Les Guignols de l'info. Par une mise en scène de la sphère médiatique française, cette émission articule parodie du dispositif médiatique, parodie des activités communicationnelles et parodie des discours associés aux acteurs de l'espace public. Recourant de façon importante à l'effet d'amplification, la parodie rend particulièrement saillant les aspects les plus conventionnels de la communication. Profitant de cet effet de loupe, une description détaillées des opérations linguistiques, discursives et interactionnelles participant de l'épisode narratif met en lumière deux fonctions possibles de la narration en situation d'entretien : réorienter l'interaction en sa faveur et configurer les cadres référentiels d'une argumentation.