Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.

Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The aim of this study was to characterize in airway and alveolar epithelial cells the enzymes responsible for this activation. BEAS-2B and A549 cells, which both produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells, respectively. Both cell lines were able to convert exogenously added Big ET-1 (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing. The conversion was inhibited by phosphoramidon in both cell lines with an IC50 approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B and A549 cells was not inhibited by thiorphan, and phosphoramidon showed inhibition only at high concentration (>100 microM). Western blotting following electrophoresis in reducing conditions demonstrated a protein of MR 110 corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE-1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP.

Intégrer les proches dans l'abord des addictions aux jeux d'argent : l'expérience d'une unité spécialisée en Suisse romande

Cet article décrit les procédures de soins mises en place depuis 10 ans au Centre de jeu excessif à Lausanne pour intégrer les proches dans le traitement des addictions aux jeux d'argent. Ce bilan permet de dégager également des pistes pour améliorer cette prise en compte des proches, que ce soit au niveau de la formation ou au niveau politique. (réd.).

Front-crawl instantaneous velocity estimation using a wearable inertial measurement unit.

Monitoring the performance is a crucial task for elite sports during both training and competition. Velocity is the key parameter of performance in swimming, but swimming performance evaluation remains immature due to the complexities of measurements in water. The purpose of this study is to use a single inertial measurement unit (IMU) to estimate front crawl velocity. Thirty swimmers, equipped with an IMU on the sacrum, each performed four different velocity trials of 25 m in ascending order. A tethered speedometer was used as the velocity measurement reference. Deployment of biomechanical constraints of front crawl locomotion and change detection framework on acceleration signal paved the way for a drift-free integration of forward acceleration using IMU to estimate the swimmers velocity. A difference of 0.6 ± 5.4 cm · s(-1) on mean cycle velocity and an RMS difference of 11.3 cm · s(-1) in instantaneous velocity estimation were observed between IMU and the reference. The most important contribution of the study is a new practical tool for objective evaluation of swimming performance. A single body-worn IMU provides timely feedback for coaches and sport scientists without any complicated setup or restraining the swimmer's natural technique.

Prospective monitoring of cefepime in intensive care unit adult patients

Rapport de synthèse :Le céfépime a été associé à un taux de mortalité supérieur à celui des autres bêta-lactamines chez les patients traités pour un sepsis sévère. Une des hypothèses avancées pour expliquer ces échecs thérapeutiques sont de possibles effets secondaires cachés (par ex. neurologiques) ou des paramètres pharmacocinétiques/pharmacodynamiques (PK/PD) inadaptés. Le présent travail a étudié cette problématique en mesurant prospectivement la pharmacocinétique du céfépime chez 21 patients consécutifs hospitalisés aux soins intensifs adultes (SIAD) pour une pneumonie nosocomiale. La population étudiée avec un âge médian 55,1 ans, a reçu par voie intraveineuse du céfépime à raison de 2 g toutes les 12 heures pour une clairance de la créatinine (Clcr)>50 mI/ min, et 2 g toutes les 24 heures ou 36 heures pour une Clcr<50 ml /min. Les taux plasmatiques de céfépime ont été mesurés à plusieurs reprises avant et après administration du médicament après la lèoe dose et à l'état d'équilibre par chromatographie en phase liquide à haute pression. Les taux plasmatiques ont considérablement varié entre les patients. Cent pour cent (21/21) des patients ont eu une durée appropriée d'antibiothérapie avec des taux plasmatiques supérieures à la CMI du céfépime (T>CMI>50%) pour les agents pathogènes retrouvés dans cette étude (CMI<4 mg/I), mais seulement 45-65% d'entre eux ont eu une couverture appropriée pour les agents pathogènes potentiels présentant une CMI> 8 mg/I pour le céfépime. Deux patients avec une insuffisance rénale (Clcr<30 ml/min) ont présenté des symptômes compatibles avec une épilepsie non-convulsive (état confusionnel et myoclonies) attribuée dans un 2ème temps à une toxicité du céfépime après que les taux plasmatiques aient été communiqués aux soignants qui ont suspendu l'antibiothérapie avec disparition des symptômes. Les résultats de cette étude empirique confirment l'existence d'effets secondaires cachés et de paramètres PK/PD inappropriés (pour les agents pathogènes ayant des CMI de limite supérieure) dans notre population de SIAD. En outre, ils mettent en évidence une fenêtre thérapeutique efficace pour une posologie de céfépime de 2 g toutes les 12 heures chez les patients ayant une Clcr>50 ml/min infectés par des pathogènes avec des CMI pour le céfépime <4 mg/I. Les échecs thérapeutiques constatés dans cette étude sont probablement liés à des taux sériques inadaptés, résultant de la difficulté de prescription dans les situations cliniques complexes. Dans ce contexte, un prompt dosage plasmatique du céfépime doit être considéré en cas de diminution de la Clcr ou en présence de CMI élevées.

Accurate memory for object location by individuals with intellectual disability: Absolute spatial tagging instead of configural processing?

Using head-mounted eye tracker material, we assessed spatial recognition abilities (e.g., reaction to object permutation, removal or replacement with a new object) in participants with intellectual disabilities. The "Intellectual Disabilities (ID)" group (n=40) obtained a score totalling a 93.7% success rate, whereas the "Normal Control" group (n=40) scored 55.6% and took longer to fix their attention on the displaced object. The participants with an intellectual disability thus had a more accurate perception of spatial changes than controls. Interestingly, the ID participants were more reactive to object displacement than to removal of the object. In the specific test of novelty detection, however, the scores were similar, the two groups approaching 100% detection. Analysis of the strategies expressed by the ID group revealed that they engaged in more systematic object checking and were more sensitive than the control group to changes in the structure of the environment. Indeed, during the familiarisation phase, the "ID" group explored the collection of objects more slowly, and fixed their gaze for a longer time upon a significantly lower number of fixation points during visual sweeping.

Broadening the horizon--level 2.5 of the HUPO-PSI format for molecular interactions.

BACKGROUND: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. RESULTS: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. CONCLUSION: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel.

Ispol'zovanie metodov teorii vosstanovleniia v modeliakh optimal'nogo dobyvaniia pishchi [Restoration theory in models of optimal feeding behavior]

The method of stochastic dynamic programming is widely used in ecology of behavior, but has some imperfections because of use of temporal limits. The authors presented an alternative approach based on the methods of the theory of restoration. Suggested method uses cumulative energy reserves per time unit as a criterium, that leads to stationary cycles in the area of states. This approach allows to study the optimal feeding by analytic methods.

Construct validity of the French version of the PRWE (Patient Rated Wrist Evaluation) with the French version of the DASH (Disabilities Arm Shoulder and Hand) is good to very good in a population of patients with wrist injuries in an inpatient rehabilitation unit

Objective.- The Patient-Rated Wrist Evaluation is a specific questionnaire for the wrist [1]. It consists of 15 questions with a total score of 100. It was recently translated into French [2]. However, its validity has not been tested in this language. The Disabilities Arm Shoulder and Hand (DASH), with well-established psychometric properties, is considered as the reference questionnaire for the evaluation of upper extremities. The objective of this study is to measure the construct validity of the PRWE-F with the DASH-F in patients with wrist pathology.Patients and methods.- Fifty-one patients (40 m, 11 w, mean age 42 years), 25 fractures of the radius and 26 lesions of the carpus.Questionnaires PRWE-F and DASH-F at entry and at discharge (0 to 100). Calculation of the construct validity of the PRWE-F comparing with the DASH-F with Pearson correlation coefficients (r) at entry and at discharge. Level of significance (alpha) was set at 5%.Results.- Correlation DASH/PRWE at entry: r = 0.799 (95% CI 0.671 to 0.881), P < 0.0001. Correlation DASH/PRWE at discharge: r = 0.847 (95% CI: 0.745 to 0.910), P < 0.0001.Discussion.- The construct validity of the two instruments indicates that they measure the same concept. Our correlation between DASH-F and PRWE-F, going from 0.799 to 0.847, are comparable to those published in different languages (0.71 to 0.84) [3,4]. The questionnaires PRWE-F can thus be used in rehabilitation patients presenting with wrist pathologies; it is comparable to the DASH but described by MacDermid [1] to be more specific. Compared to the DASH it has the advantage of consisting of two dimensions. Its construct validity is excellent. This questionnaire should be evaluated in other populations, and it should be compared with hand questionnaires more specific than the DASH.

Delirium in elderly patients hospitalized in an acute care unit.

Introduction: Delirium is frequent in hospitalized older people, with incidence rate up to 40% in acute care. Delirium is associated with several adverse consequences, including increased mortality and institutionalization. This study aims to investigate the prevalence, incidence, and consequences of delirium in patients hospitalized in an acute care unit for elderly (ACE unit). Methods: Over a 3 months period, every patient (N = 93, mean age 84.1 ± 7.8 years, 66/93(71%) women) admitted to a 28-bed ACE unit were systematically assessed for delirium. Trained nurses used the Confusion Assessment Method (CAM) instrument to determine the presence of delirium at admission and on each subsequent day over patients' stay. Delirium prevalence rate was defined as the proportion of patients with a positive CAM within 24 hours of admission to the ACE unit. Delirium incidence rate was defined as the proportion of patients with a negative CAM at admission whose CAM became positive at least once during their stay. This evaluation was part of a functional assessment, including Basic Activities of Daily Life (Katz BADL, from 0 to 6, higher score indicating better function). Delirium prevention interventions and specific treatment was provided if needed. Results: Overall,25/93(27%)patients had delirium during their stay. Prevalence of delirium at admission was 10/93 (11%), with an incidence of 15/83(18%). Compared with non-delirious patients, those with delirium were more frequently men (10/25(40%) vs 17/68(25%), p <.001) and had reduced functional status at admission(BADL 2.0 ± 1.9 vs 3.6 ± 2.1, p = .004). They tended to be older (86.0 ± 6.7 vs 83.3 ± 8.1 years, p = .110). At discharge, delirium was associated with reduced functional status (BADL 2.0 ± 2.1 vs 4.3 ± 1.9, p <.001), lower rate of home discharge (6/20(30%) vs 28/65 (43%), p = .009) and increased mortality (5/25 (20%) vs 3/68 (5%), p <.001). On average, patients with delirium stayed 5.7 days longer (17.0 ± 9.8 vs 11.31 ± 6.3, p = .011). Conclusion: Delirium occurred in almost a third of these older patients, even though its incidence was relatively low in this frail population. Despite specific management, delirium remained associated with higher risk for adverse outcomes at discharge. These results suggest that early preventive interventions, implemented as soon as possible after hospital admission, might be needed in similar population to achieve better outcomes. Effectiveness of such interventions will be evaluated in future studies.

Processing of the circumsporozoite protein in infected hepatocytes is not dependent on aspartic proteases

CD8(+) T cells play a major role in the protective immune response against the liver stage of malaria. It was previously shown that the circumsporozoite protein (CSP) is processed and presented to specific T cells by both traversed and infected hepatocytes, but their respective antigen processing requirements were not completely defined. In the present study, we show that in vitro processing of the Plasmodium berghei CSP by infected mouse primary hepatocytes is exclusively dependent on proteasomes, while aspartic proteases are also needed in the case of traversed hepatocytes