Asenapine treatment and health-related quality of life in patients experiencing bipolar I disorder with mixed episodes: post-hoc analyses of pivotal trials.

OBJECTIVE: To evaluate the baseline impact of episode type (manic vs. mixed), defined using DSM-IV-TR criteria, in bipolar I disorder (BD-I) on health-related quality of life (HRQoL), and to investigate the differential effect of asenapine vs. placebo and olanzapine on HRQoL in BD-I patients with mixed episodes. METHODS: In two identically designed 3 week, randomized, double-blind, flexible-dose, placebo- and olanzapine-controlled trials of asenapine, HRQoL was assessed using the 36-item Short-Form Health Survey (SF-36v2) administered at baseline and endpoint. In addition to evaluating the impact of clinical presentation (manic vs. mixed episodes) on baseline HRQoL, the impact of treatment intervention on HRQoL was assessed via analysis of covariance models at study endpoint, with center and treatment-by-diagnosis interaction as fixed effect and baseline score as covariates. RESULTS: A total of 960 BD-I patients (asenapine: 372; olanzapine: 391; placebo: 197) were included in the two studies. The observed burden of disease on HRQoL was substantial compared to general US population norms, particularly in patients experiencing mixed episodes. The greatest impairments were observed in the mental domains of HRQoL (Mental Component Summary scores: mixed = 31.9; manic = 42.8). For patients with mixed episodes, when compared to olanzapine, asenapine treatment was associated with improvements noted in every domain, which did not reach statistical significance except for Vitality (asenapine = 55.0, olanzapine = 51.3; p = 0.014) and Role-Emotional (asenapine = 44.8, olanzapine = 40.3; p = 0.020). Compared to placebo patients with mixed episodes, asenapine treatment provided significant improvements (p < 0.05) in Bodily Pain (asenapine = 50.9, placebo = 45.9), Social Functioning (asenapine = 44.1, placebo = 39.6) and Mental Health (asenapine = 46.6, placebo = 42.7) by Week 3; by comparison, olanzapine treatment did not lead to significant improvements in any domain of HRQoL compared to placebo. CONCLUSIONS: Post-hoc analyses of two trials showed that BD-I patients with mixed episodes reported considerable impairments in HRQoL compared to patients with manic episodes. At 3 weeks, in patients with mixed episodes, asenapine was shown to lead to significant improvements in HRQoL compared to olanzapine and placebo. Results from these post-hoc analyses should be confirmed in prospective studies. TRIAL REGISTRATION: NCT00159744, NCT00159796.

Indirect comparison of clobazam and other therapies for Lennox-Gastaut syndrome.

OBJECTIVE: In the absence of head-to-head trials, it is not feasible to make direct comparisons of antiepileptic therapies for the treatment of Lennox-Gastaut syndrome (LGS). We conducted indirect comparisons of the relative efficacies of clobazam, felbamate, lamotrigine, topiramate, and rufinamide as adjunctive treatments for LGS. METHODS: Clinical studies of LGS patients were identified in a 2009 Cochrane review and by electronic database search. Five randomized controlled trials were included in this systematic review, which reports findings from indirect comparisons between clobazam and other approved adjunctive LGS therapies (felbamate, lamotrigine, topiramate, rufinamide) in the United States and Europe. As outcomes were not uniformly reported across studies, the primary efficacy endpoint from each trial was transformed into Cohen's d effect size, to facilitate indirect comparisons. Typical interpretations of Cohen's d results are as follows: d < 0.2, change not detectable; 0.2 ≤ d < 0.5, small change; 0.5 ≤ d < 0.8, moderate change; and 0.8 ≤ d, large change. RESULTS: High-dosage clobazam (1.0 mg/kg/day) was found to have the strongest treatment effect vs placebo (effect size 0.80), with moderate effects (effect sizes >0.50) for medium-dosage clobazam (0.5 mg/kg/day) and rufinamide. Felbamate, lamotrigine, and topiramate had low effect sizes. Indirect comparisons of numbers of total seizures and tonic-atonic seizures ('drop attacks') demonstrated superiority of both clobazam dosages over all comparators. CONCLUSIONS: High- and medium-dosage clobazam was estimated to be more efficacious than other LGS treatments. Our analysis relied on published data and could not draw on direct head-to-head data of clobazam with alternatives. Further comparative research is ongoing to assess the usefulness of clobazam for LGS.

Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: results from post hoc analyses.

BACKGROUND: The efficacy of agents useful for mania is largely unproven in patients with mixed episodes. METHODS: The efficacy of asenapine in the treatment of mixed episodes was assessed using post hoc analyses on pooled data from two identically designed 3-week, randomized, double-blind, flexible dose, placebo- and olanzapine-controlled trials and their 9-week, double-blind olanzapine-controlled extension study. Efficacy was measured by changes on Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores, and was analysed through analysis of covariance on observed cases of the intent-to-treat dataset. RESULTS: In the intent-to-treat population, 295 patients had a DSM-IV-TR mixed episode (placebo: 66; olanzapine: 122; asenapine: 107) in the 3-week trials. Of these, 102 patients (olanzapine: 56; asenapine: 46) entered the 9-week extension study. At week 3, decreases in YMRS and MADRS total scores, were significantly (p<0.01) greater with asenapine (YMRS: -15.0; MADRS: -8.2) versus placebo (YMRS: -11.5; MADRS: -4.5); olanzapine did not separate from placebo (YMRS: -13.3; MADRS: -6.5). At week 12, further decreases in YMRS and MADRS total scores were observed with asenapine (YMRS: -22.4; MADRS: -11.9); non-statistically different from olanzapine (YMRS: -20.2; MADRS: -7.9). LIMITATIONS: Results are from post hoc analyses of trials that were not designed to specifically evaluate mixed episodes. CONCLUSIONS: These exploratory analyses provide supportive evidence for the efficacy of asenapine in treating the associated symptoms of mania and depression in bipolar I patients with mixed episodes.

Shortening the VSP-A: preliminary development of the VSP-A12, a 12-item short-form.

The 'Vécu et Santé Perçue des Adolescents' (VSP-A) questionnaire is a French generic self-administered health-related quality of life (HRQL) instrument for adolescents which comprises 40 items, allowing the calculation of six dimensions as well as an index. Regression methods were used to select 12 items from the VSP-A to reproduce its HRQL index. The resulting 12-item short-form (VSP-A12) achieved an adjusted R2 of 0.907 in prediction of the VSP-A index. Scoring algorithm used to score this 12-item index achieved a R2 of 0.901 with the VSP-A index when cross-validated in the validation sample (n = 2941). Numerous tests of empirical validity previously published for the VSP-A were replicated for the VSP-A12, including comparisons between groups known to differ in terms of gender, age or health status. All the significant results shown by the VSP-A index were also encountered by the VSP-A12 summary measure. The ability of VSP-A12 to discriminate between healthy and ill adolescents was also proven. A test-retest correlation (4 weeks) of 0.745 was observed for the 12-item HRQL index in the target population (n = 664). Average score for this shorter index closely mirrored VSP-A index, although standard deviation was always greater for the VSP-A12.

Depression and subjective quality of life in chronic phase schizophrenic patients.

OBJECTIVE: To evaluate the influence of depression on subjective quality of life in schizophrenic patients. METHOD: Sixty-seven schizophrenic patients in a stabilized phase were included. Schizophrenic symptoms were evaluated using the Positive and Negative Symptoms Scale (PANSS). The subjective quality of life was evaluated using the short version of the Lehman quality of life scale (QoLI). Depression was evaluated using the Calgary Depression Scale for Schizophrenia (CDSS) and extrapyramidal effects with the Extrapyramidal Symptoms Rating Scale (ESRS). RESULTS: The PANSS total score, PANSS general psychopathology subscore, PANSS depression factor, the total CDSS and some ESRS scores were negatively correlated with the overall life satisfaction score. The CDSS score was negatively correlated with all except one QoLI score. QoLI scores were significantly lower in depressed patients, and this result remained consistent for four QoLi dimensions when adjusted on ESRS and PANSS scores. When analysing the association between high depression scores and high parkinsonism scores with reduced quality of life, multivariate analysis showed that depression was the main explanatory factor: the CDSS total score explained 22% of the variance of the overall subjective quality of life score. The patient questionnaire at the ESRS explained 10.5% of the variance of the 'mental and physical health' QoLI score. CONCLUSION: In schizophrenic patients, depressive symptoms should be focused because of their strong association to overall subjective quality of life.

Development and validation of a patient-based health-related quality of life questionnaire in schizophrenia: the S-QoL.

We developed a self-administered instrument to assess health-related quality of life (HRQL) among people with schizophrenia. The S-QoL, based on Calman's approach to the subject's point of view, is a multidimensional instrument that is sensitive to change. The scale is a 41-item questionnaire with eight subscales (psychological well-being, self-esteem, family relationships, relationships with friends, resilience, physical well-being, autonomy and sentimental life) and a total score. In-depth interviews with patients determined the pertinent issues for item development. The validation study, performed with 207 patients, showed high internal consistency reliability, reproducibility and responsiveness. Construct validity was confirmed using established clinical and HRQL measures. S-QoL covers domains that differ from areas tapped in other measures, with greater responsiveness. The S-QoL is an efficient instrument for the measurement of the impact of schizophrenia on individuals' lives.

Cytogenetic monitoring of industrial radiographers using the micronucleus assay.

Industrial radiography is the process of using either gamma-emitting radionuclide sources or X-ray machines to examine the safety of industrial materials. Industrial radiographers are among the radiation workers who receive the highest individual occupational radiation doses. To assess occupationally induced chromosomal damage, we performed the cytokinesis-block micronucleus (CBMN) assay in peripheral lymphocytes of 29 male industrial radiographers, exposed to ionizing radiation for 12.8 years+/-11.2, in comparison with 24 gender-, age-, and smoking habits-matched controls. The CBMN assay was combined with fluorescent in situ hybridization with a pan-centromeric DNA probe in 17 exposed subjects and 17 controls randomized from the initial populations. The mean cumulative equivalent dose, recorded by film dosimeters, was 67.2 mSv+/-49.8 over the past 5 years. The mean micronucleated binucleated cell rate (MCR) was significantly higher in the industrial radiographers than in the controls (10.7 per thousand +/-5.2 versus 6.6 per thousand +/-3.1, P=0.009); this difference was due to a significantly higher frequency of centromere-negative micronuclei (C-MN) in exposed subjects than in controls (8.5 per thousand +/-4.9 versus 2.2 per thousand +/-1.6, P<0.001). The two populations did not significantly differ in centromere-positive micronuclei (C+MN) frequency. These findings demonstrate a clastogenic effect in lymphocytes of industrial radiographers. MCR significantly positively correlated with age in the two groups. After correction for the age effect, MCR did not correlate with duration of occupational exposure. No correlation between radiation doses and MCR, C-MN, and C+MN frequencies was observed. In addition to physical dosimetry records, the enhanced chromosomal damage in lymphocytes of industrial radiographers emphasizes the importance of radiation safety programs.

[Mandatory notification of HIV infection. Epidemiologic justifications and ethical questioning]. / Déclaration obligatoire de l'infection par le VIH. Justifications épidémiologiques et interrogations éthiques.

Since the appearance in May 1999 of the two decrees on the application of the law relative to the reinforcement of sanitation quality control established in July 1998, the disclosure of HIV infection "irregardless of the stage" has become mandatory. This is the first time that it is imposed that one must declare a serologic diagnosis, that is to say an infection in the asymptomatic stage. The sensitive nature of all of the information available on AIDS provides an explanation for the numerous contradictory reactions linked to this decision. We attempt to organise the arguments brought forth according to two approaches: 1) the epidemiological arguments that justify the compilation of the precise data thought to be necessary for the follow-up of the disease and for the implementation of well-targeted prevention actions; and 2) the ethical reservations concerning such an imposed measurement, as well as the questions related to anonymity and confidentiality.

[Validation of the French language version of the Parkinson's Disease Questionnaire - PDQ-39]. / Validation en langue française d'un questionnaire de qualité de vie dans la maladie de Parkinson: le Parkinson's Disease Questionnaire - PDQ-39.

After Alzheimer's disease, Parkinson's disease (PD) is the second most frequent degenerative disease of the central nervous system. The consequences of PD at the functional, social and emotional levels warrant a better understanding the patient's perceptions as measured using a specific instrument rather than restricting the medical approach to the clinical evaluation of the motor component. In 1996, we began implementation of a project to transculturally validate the single specific instrument that had been published and was available at that time: PDQ-39. The scale consists in a 39-item questionnaire enabling determination of an overall quality-of-life score and scores for 8 specific dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort. Eighty-nine patients taking part in an open-label study of the safety of a combination of pergolide and dopa therapy were included and followed up on D15 and after 8 weeks. The process of "Forward-Backward" translation, conducted in close liaison with the authors, enabled semantic and linguistic validation of the French language version. The content was validated by PD experts. At baseline, the patients presented quality-of-life scores that were particularly impaired for the dimensions exploring Mobility, Emotional well-being and Bodily discomfort. The main metric properties of the scale were confirmed. The PDQ-39 scores were closely correlated with the related concepts investigated by generic scale, SF-36. The PDQ-39 scores were correlated with the "Mental and Mood Status", "Everyday Activities" and "Motor Status" dimensions determined by the UPDRS. The reliability, expressed by Cronbach coefficients alpha, showed strong consistency of the instrument, very similar to the data for the original version. In contrast to what was observed with SF-36, the scale was particularly sensitive to clinical changes. The initial results make PDQ-39 a precious tool for the optimization of management of patients presenting with PD.

Antibodies to phosphatidylethanolamine as the only antiphospholipid antibodies found in patients with unexplained thromboses.

The objective of this study was to assess the interest of antiphosphatidylethanolamine antibodies (aPE) in unexplained thrombosis (UT) defined as thrombotic episode without any of the main autoimmune and hereditary thrombophilic defects. Results from 98 UT were compared to those of (I) 142 patients with thrombophilia: 67 antiphospholipid syndrome (APS) and 75 hereditary hemostatic defects (HHD); (II) 110 patients without thrombosis: 60 with systemic lupus erythematosus (SLE) and 50 with infectious diseases (ID). As compared to controls (100 blood donors), aPE prevalence was significantly higher in both autoimmune contexts (APS: 43%; SLE: 40%, p<0.0001) and among non-autoimmune pathologies, only in UT (18%, p = 0.001) conversely to HHD (8%) or ID (10%). aPE prevalence in UT was not statistically different from that found in Primary APS (32%, p = 0.076) but lower than in Secondary APS (65%, p <0.005). In UT, aPE were mainly of IgM isotype like in Primary APS and they were found alone whereas in SLE they were always associated with classical antiphospholipid antibodies. No significant association was found between any isotype of aPE and a site of thrombosis in UT as well as in APS. In conclusion, this study demonstrates an increase of the prevalence of aPE in patients with unexplained thrombosis. Thus, aPE investigation appears to be of interest in UT and their persistent presence could define a biological variant of APS.

Health-related quality of life reported by French adolescents: a predictive approach of health status?

PURPOSE: To examine the relevance of a self-administered multidimensional instrument to the discrimination of illness and health among adolescents in South-eastern France. METHODS: We show the results of a self-reported HRQL assessment by the Vécu et Santé Perçue de l'Adolescent (VSP-A) multidimensional questionnaire, conducted on a population of 3061 adolescents. The VSP-A produces a score for each of the seven dimensions (relationships with friends, relationships with parents, school life, inaction, psychological distress, future, and energy/vitality) and a global score. The result is compared with the answers of the parents to the same multidimensional HRQL questionnaire reworded for them (VSP-P) and to the perceived health self-reported by the adolescents on a visual analogue scale (VAS). The adolescents filled both the VSP-A and VAS questionnaires twice at a 1-month interval. RESULTS: A total of 2941 adolescents completed the questionnaire correctly, and 1760 VSP-P questionnaires were filled out by their parents. The global HRQL score as well as the dimension scores from the parents' assessment were significantly different from those of the adolescents. At the inception, using three approaches (self-reported VAS, VSP-A, and VSP-P), it was possible to discriminate between ill and healthy adolescents. Nevertheless, the VSP-A completed at the inception is the only of the three approaches that can point out the adolescents who will become ill during the following month. Furthermore, the results reported by VSP-A largely agree with literature. CONCLUSION: The VSP-A could provide a comprehensive approach of HRQL of young people in both health prevention and the health care system.

A heat labile soluble factor from Bacteroides thetaiotaomicron VPI-5482 specifically increases the galactosylation pattern of HT29-MTX cells.

The aim of this work was to set up and validate an in vitro model to study a molecular response of an intestinal host cell line (HT29-MTX), to a non-pathogen microflora component. We found that Bacteroides thetaiotaomicron strain VPI-5482 had the capacity to change a specific glycosylation process in HT29-MTX cells via a mechanism that involved a soluble factor. Differentiated HT29-MTX cells were grown in the presence of 20% of spent culture supernatant from the B. thetaiotaomicron during 10 days. Glycosylation processes were followed using a large panel of lectins and analysed using confocal microscopy, western blotting and flow cytometry techniques. Our results show that a B. thetaiotaomicron soluble factor modified specifically the galactosylation pattern of HT29-MTX cells, whereas other glycosylation steps remained mainly unaffected. Further characterization of this soluble factor indicates that it is a heat labile, low molecular weight compound. Reverse transcript-PCR (RT-PCR) analysis was unable to show any significant change in mRNA expression level of the main galactosyltransferases expressed in HT29-MTX cells. By contrast, galactosyltransferase activities dramatically increased in HT29-MTX cells treated by the soluble extract of B. thetaiotaomicron, suggesting a post-translational regulation of these activities. Our in vitro model allowed us to study the cross-talk between a single bacteria and intestinal cells. The galactosylation process appears to be a target of this communication, thus uncovering a new window to study the functional consequences of co-operative symbiotic bacterial-host interactions.

Rate of abnormal osteoarticular radiographic findings in pediatric patients.

OBJECTIVE: The objective of our study was to assess the rate of abnormal radiographic findings in the most frequent osteoarticular locations of traumatic injury in a pediatric population. SUBJECTS AND METHODS: During two periods of 12 weeks each, all patients admitted to the pediatric emergency department for osteoarticular trauma who underwent radiography were prospectively included in this study. A connection was drawn between the rate of abnormal radiographic findings for the seven most frequently radiographed locations and the clinical findings. RESULTS: Of 3128 locations of trauma in 2470 children, only 22% of the radiographic examinations were considered to reveal abnormal findings. In decreasing order, the hand and fingers, the ankle, the wrist, the knee, the elbow, the foot and toes, and the forearm were the most frequently examined locations. The rate of abnormal findings was 25.7% for the hand and fingers, 9.0% for the ankle, 42.5% for the wrist, 9.5% for the knee, 33.3% for the elbow, 18.3% for the foot, and 43.2% for the forearm. When only the direct sign of fracture was taken into account, these rates decreased for the ankle and knee to 2.6% and 1.9%, respectively. There was always a significant link between the degree of clinical suspicion and the rate of abnormal radiographic findings. However, fewer than 50% of the cases with high clinical suspicion of fracture were radiographically confirmed. CONCLUSION: It appears necessary, especially in cases of lower limb trauma, to evaluate clinical tests, including the implementation of the Ottawa ankle rules, to reduce the number of unnecessary radiographic examinations. This reduction will improve some parameters of children's quality of life and will significantly decrease the cost of emergency care.

Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age.

OBJECTIVE: To compare the value of 17 IVF variables, including a new mean score of transferred embryos (MSTE), in predicting pregnancy rate. DESIGN: Retrospective study. SETTING: Private IVF unit. PATIENT(S): Women who underwent 10,000 embryo transfers. MAIN OUTCOME MEASURE(S): Duration of infertility, type of infertility, female age, rank of IVF attempt, type of ovarian treatment, progesterone level, sperm count, sperm motility, sperm morphology, number of retrieved oocytes, number of mature oocytes, maturation rate, number of embryos obtained, fertilization rate, number of transferred embryos, cumulative embryo score (CES), mean score of transferred embryos (MSTE), and pregnancy rate. RESULT(S): Outcome of IVF-ET was significantly correlated with female age, type of infertility, number of retrieved oocytes, number of mature oocytes, maturation rate, embryos obtained, fertilization rate, transferred embryos, CES, and MSTE. Multivariate analysis demonstrated that MSTE was a better predictor of pregnancy than the number of transferred embryos and female age. CONCLUSION(S): Embryo quality is the best predictor of pregnancy. The embryo score described herein should be used in IVF-ET programs to choose the best embryos for transfer.

Validation of a French health-related quality of life instrument for adolescents: the VSP-A.

The French Health Ministry, stating the limits of traditional indicators to take into account the different aspects of adolescent health, declared adolescent health status assessment as a priority. Thus a French health-related quality of life (HRQL) generic self-administered indicator was developed on the adolescent's viewpoint for healthy and ill adolescents of 11-17: the VSP-A, Vécu et Santé Perçue de l'Adolescent, intended to be used as a discriminative, predictive and evaluative instrument. This paper reports the validation study of the 40-item VSP-A including 2941 adolescents. Six dimension scores were computed: psychological well-being, energy, friends, parents, leisure, school, as well as an index. Content and construct validity were confirmed. Factorial validity was shown. As expected, scale scores were significantly associated with a one-item global well-being visual analogue scale (r = 0.53; p < 0.001) and with a self-esteem score (r = 0.62; p < 0.001). On the VSP-A index, girls and older adolescents were found to have the lowest scores. The VSP-A is reliable in terms of internal consistency (Cronbach's alpha = 0.83) and test-retest results (r = 0.69; p < 0.001). The ability of VSP-A, filled in less than 15 min, was shown to discriminate between ill and healthy adolescents, and to predict an impairment of their health status. The next phase of the research involves testing in various populations and more specifically in populations with diverse acute and chronical health conditions, so as to refine the content of the instrument and to add much to what is known about the sensitivity to changes of the VSP-A scores in patients who are under treatment.

Apical secretion and sialylation of soluble dipeptidyl peptidase IV are two related events.

The role of glycans in the apical targeting of proteins in epithelial cells remains a debated question. We have expressed the mouse soluble dipeptidyl peptidase IV (DPP IV ectodomain) in kidney (MDCK) and in intestinal (Caco-2) epithelial cell lines, as a model to study the role of glycosylation in apical targeting. The mouse DPP IV ectodomain was secreted mainly into the apical medium by MDCK cells. Exposure of MDCK cells to GalNac-alpha-O-benzyl, a drug previously described as an inhibitor of mucin O-glycosylation, produced a protein with a lower molecular weight. In addition this treatment resulted in a decreased apical secretion and an increased basolateral secretion of mouse DPP IV ectodomain. When expressed in Caco-2 cells, the mouse DPP IV ectodomain was secreted mainly into the basolateral medium. However, BGN was still able to decrease the amount of apically secreted protein and to increase its basolateral secretion. Neuraminidase digestion showed that the most striking effect of BGN was a blockade of DPP IV sialylation in both MDCK and Caco-2 cells. These results indicate that a specific glycosylation step, namely, sialylation, plays a key role in the control of the apical targeting of a secreted DPP IV both in MDCK and Caco-2 cells.

[Perceived health and migration: a new sanitary approach?]. / Santé perçue et migration : une nouvelle approche pour l'intégration sanitaire ?

BACKGROUND: Six percent of the French population is foreign. Paradoxically, there are in France few recent data about the health of these communities. Because a lot of different foreign communities are living in Marseille, it seemed important for us to examine the health of one of these populations. The difficulties encountered in studying the health status in the general population allow us to propose a measure based on perceived health opinion. Our first objective was to state that perceived health status of one community differs between its original country and its emigration country, taking into account the level of morbidity. Our second objective was to show that the perceived health status in the emigration population was close to the one observed in France. METHODS: Two cross-sectional studies were performed in the Comoro Islands and in Marseille, a French south eastern city. The perceived health was assessed with the Duke Health Profile (DHP); the objective health was assessed by a specific questionnaire developed in the USA: the Ridit. The comparisons were conducted, taking into account the major confounding factors. RESULTS: Emigrated people relate higher perceived health status, than those living in the Comoro Islands, for the main dimensions assessed by DHP: physical (71.0 +/- 23.8 vs. 55.9 +/- 23.0), mental (74.6 +/- 19.3 vs. 50.0 +/- 18.5), general health (68.3 +/- 16.3 vs. 61.4 +/- 12.7) and perceived health (62.7 +/- 32.9 vs. 57.1 +/- 48.2). Social health score is the only one which is lower (59.2 +/- 21.8 vs. 77.6 +/- 18.3). The health status levels of the emigrated people are close to those reported in France. The variations of perceived health scores are coherent with those of the objective health indicators. CONCLUSIONS: If these results were confirmed, then this approach, based on self perceived health assessment, could be recommended to study health needs, and the management care, prevention and health promotion impact among these specific communities.

Rotavirus spike protein VP4 is present at the plasma membrane and is associated with microtubules in infected cells.

VP4 is an unglycosylated protein of the outer layer of the capsid of rotavirus. It forms spikes that project from the outer layer of mature virions, which is mainly constituted by glycoprotein VP7. VP4 has been implicated in several important functions, such as cell attachment, penetration, hemagglutination, neutralization, virulence, and host range. Previous studies indicated that VP4 is located in the space between the periphery of the viroplasm and the outside of the endoplasmic reticulum in rotavirus-infected cells. Confocal microscopy of infected MA104 monolayers, immunostained with specific monoclonal antibodies, revealed that a significant fraction of VP4 was present at the plasma membrane early after infection. Another fraction of VP4 is cytoplasmic and colocalizes with beta-tubulin. Flow cytometry analysis confirmed that at the early stage of viral infection, VP4 was present on the plasma membrane and that its N-terminal region, the VP8* subunit, was accessible to antibodies. Biotin labeling of the infected cell surface monolayer with a cell-impermeable reagent allowed the identification of the noncleaved form of VP4 that was associated with the glycoprotein VP7. The localization of VP4 was not modified in cells transfected with a plasmid allowing the expression of a fusion protein consisting of VP4 and the green fluorescent protein. The present data suggest that VP4 reaches the plasma membrane through the microtubule network and that other viral proteins are dispensable for its targeting and transport.

[Molecular signals in protein sorting in epithelial cells: implication of the transmembrane domain and the post-translational process]. / Signaux moléculaires de tri des protéines dans les cellules épithéliales: implication du domaine transmembranaire et des processus de maturation post-traductionnels.

Protein sorting in epithelial cells is the major event that drive the onset and the maintenance of the functional cell polarity. A lot of interdependent steps are involved in protein sorting and targeting. Recent data describing the last results obtained in this field will be reviewed in the first part of this article. Molecular signals harbored by proteins to specify their destination are thought to be the driven force to sort given protein in a given pathway. The basolateral targeting signals so far identified are known for several years and are of the same nature, whereas apical targeting signals are still discussed and are of diverse molecular nature. Dipeptidyl peptidase IV (DPP IV/CD26) targeting signals have not been described so far and it will be interesting to study these signals, since the protein reach the apical membrane of epithelial cells through different pathways that strongly depend on the cell type considered. These different pathways result in DPP IV membrane localizations that may explain the multifunctional properties of DPP IV such as enzymatic digestion, interaction with extracellular matrix proteins, capture and transport of circulating proteins. We have undertaken the study of DPP IV molecular targeting signals and we will described here how the transmembrane domain and the glycosylation of the ectodomain may be involved in DPP IV apical targeting, with a special reference to the cell type specificity.