Impact of international consensus guidelines on antiviral therapy of chronic hepatitis C patients in Switzerland.

To assess the impact of international consensus conference guidelines on the attitude of Swiss specialists when facing the decision to treat chronic hepatitis C patients. Questionnaires focusing on the personal situation and treatment decisions were mailed to 165 patients who were newly diagnosed with hepatitis C virus (HCV) infection and enrolled into the Swiss Hepatitis C Cohort Study during the years 2002-2004. Survey respondents (n = 86, 52.1%) were comparable to non-respondents with respect to severity of liver disease, history of substance abuse and psychiatric co-morbidities. Seventy percent of survey respondents reported having been offered antiviral treatment. Patients deferred from treatment had less advanced liver fibrosis, were more frequently infected with HCV genotypes 1 or 4 and presented more often with a history of depression. There were no differences regarding age, socio-economic background, alcohol abuse, intravenous drug abuse or methadone treatment when compared with patients to whom treatment was proposed. Ninety percent of eligible patients agreed to undergo treatment. Overall, 54.6% of respondents and 78.3% of those considered eligible had actually received antiviral therapy by 2007. Ninety-five percent of patients reported high satisfaction with their own hepatitis C management. Consistent with latest international consensus guidelines, patients enrolled in the Swiss Hepatitis C Cohort with a history of substance abuse were not withheld antiviral treatment. A multidisciplinary approach is warranted to provide antiviral treatment to patients suffering from depression.

Ultrastructural study of the TG180 murine sarcoma cell invasion by Toxoplasma gondii: comparison between in vivo and in vitro cell cultures

Infection of non-adherent TG180 murine sarcoma cells with Toxoplasma gondii was compared, at the ultrastructural level, in both in vivo and in vitro conditions. Suspensions of 3.0 x 10(6) TG180 cells infected in vitro with 1.0 x 10(6) parasites of the RH strain were harvested between the first and 6th day post-infection and processed for transmission electron microscopy. In vivo infection was made by intraperitoneal inoculation in mice of 1.0 x 10(6) TG180 cells, that were co-inoculated with a parasite suspension at the same cell concentration. Cells were harvested 10, 20, 30 min and 24, 48 h post-inoculation and processed for transmission electron microscopy at the same conditions of the in vitro culture. It was observed TG180 murine sarcoma cells with intense and equivalent intracellular parasitism in both conditions. Host cells with parasitophorous vacuoles containing up to 16 parasites, as well as parasites undergoing mitoses or presenting a bradyzoite-like morphology, were frequently seen in both culture methods.

Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.

IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when to start treatment; what treatment to start; the use of laboratory monitoring tools; and managing treatment failure, switches, and simplification. DATA SOURCES, STUDY SELECTION, AND DATA SYNTHESIS: An International Antiviral Society-USA panel of experts in HIV research and patient care considered previous data and reviewed new data since the 2012 update with literature searches in PubMed and EMBASE through June 2014. Recommendations and ratings were based on the quality of evidence and consensus. RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of reasons for failure before consideration of switching therapy. Regimen switches for adverse effects, convenience, or to reduce costs should not jeopardize antiretroviral potency. CONCLUSIONS AND RELEVANCE: After confirmed diagnosis of HIV infection, antiretroviral therapy should be initiated in all individuals who are willing and ready to start treatment. Regimens should be selected or changed based on resistance test results with consideration of dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions.

Epidermal growth factor enhances the expression of an endogenous lectin in aggregating fetal brain cell cultures.

Aggregating cell cultures prepared from fetal rat telencephalon express the two subunits [cerebellar soluble lectins (CSL) 1 and 2] of a soluble, mannose-specific endogenous lectin (CSL) in a development-dependent manner. Increased CSL synthesis was found at an early postmitotic stage as well as during the period of maximal myelination. Repetitive treatment of early cultures with epidermal growth factor (EGF, 3nM) caused a great stimulation of CSL biosynthesis. Immunocytochemical studies revealed particularly intense CSL-specific staining in small, EGF-responsive cells, presumably glial cells. Large quantities of CSL-immunoreactive material were found also in the extracellular space and on the external side of the plasma membrane, indicating abundant release of CSL. The present findings suggest that EGF or EGF-related factors in the brain are able to regulate the expression of an endogenous lectin, affecting brain ontogeny.

Differential time to positivity of blood cultures: a valid method for diagnosing catheter-related bloodstream infections in the intensive care unit

iii. Catheter-related bloodstream infection (CR-BSI) diagnosis usually involves catheter withdrawal. An alternative method for CR-BSI diagnosis is the differential time to positivity (DTP) between peripheral and catheter hub blood cultures. This study aims to validate the DTP method in short-term catheters. The results show a low prevalence of CR-BSI in the sample (8.4%). The DTP method is a valid alternative for CR-BSI diagnosis in those cases with monomicrobial cultures (80% sensitivity, 99% specificity, 92% positive predictive value, and 98% negative predictive value) and a cut-off point of 17.7 hours for positivity of hub blood culture may assess in CR-BSI diagnosis.

Cultures jeunes et religions en Europe

Après la révolution religieuse des années 60, une nouvelle religiosité est-elle née ? Cette question est au coeur du livre. Il met, en effet, en scène les jeunes des années 80, les filles et les fils de la génération d'après-guerre, celle de Mai 68. Les parents ont pris leurs distances avec les différentes formes institutionnelles de l'autorité, y compris celle des Églises. Ils avaient été laissés libres de s'initier à une voie « spirituelle » : liberté de conscience et autonomie individuelle, deux valeurs clés attachées à la génération d'après-guerre, avaient orienté leur démarche religieuse. Les années 80 constituent de plus un contexte spécifique. Derrière le rideau de l'abondance, les contours de la précarité se dessinent. L'effondrement du mur de Berlin a entraîné celui des certitudes et des points de repère. L'apparition du sida a mis en cause le mythe dominant d'une jeunesse presque éternelle ouvrant sur une société sans âge et sans conflits de génération. Ces événements ont infléchi les quêtes de sens contemporaines. Fruit de la collaboration de vingt-deux sociologues venant de différents pays de l'Union européenne et de la Suisse, l'ouvrage, plutôt que de mettre côte à côte des observations empruntées aux pays concernés, propose des analyses transversales. Il permet ainsi de se faire une idée du changement religieux qui touche l'Europe dans son ensemble et de dégager quelques enjeux communs suscités par l'incertitude ambiante. Partant de l'analyse de la condition des jeunes dans les années 80, l'ouvrage aborde tour à tour la question de leur identité religieuse, celle de leurs systèmes de croyance, puis s'attarde sur les institutions qui ont contribué à leur socialisation religieuse. L'expérience constitue une caractéristique de la vie religieuse contemporaine, alors que la pluralité de l'offre reflète le changement socioculturel. Un chapitre est ainsi consacré à la présentation de quelques trajectoires typiques illustrant la gestion de l'incertitude dans laquelle est plongée la génération en cause. Enfin est abordée la question posée par une jeunesse qui apparaît aujourd'hui dépourvue d'encadrement institutionnel dans le champ religieux comme dans d'autres domaines : cette situation ne traduit-elle pas la crise de reproduction des institutions elles-mêmes ?

Aggregating brain cell cultures for neurotoxicological studies.

Because of the limited accessibility of the brain for experimentation, but also for ethical and economical reasons, there is considerable interest in culture models suitable for neurotoxicological research. Although it is generally accepted that in vitro models cannot cover the entire spectrum of brain functions, they have proven to be indispensable for investigations in the life sciences since the early work of Harrison (1). To date, many in vitro models of various complexity are available, ranging from monolayer cultures of immortalized cell lines to organotypic cultures. Each of these culture systems has its particularities, therefore, it is of great importance to select the model that is most appropriate for the question to be solved.

Prevalence of thinness in children and adolescents in the Seychelles: comparison of two international growth references.

BACKGROUND: : Thinness in children and adolescents is largely under studied, a contrast with abundant literature on under-nutrition in infants and on overweight in children and adolescents. The aim of this study is to compare the prevalence of thinness using two recently developed growth references, among children and adolescents living in the Seychelles, an economically rapidly developing country in the African region. METHOD: S: Weight and height were measured every year in all children of 4 grades (age range: 5 to 16 years) of all schools in the Seychelles as part of a routine school-based surveillance program. In this study we used data collected in 16,672 boys and 16,668 girls examined from 1998 to 2004. Thinness was estimated according to two growth references: i) an international survey (IS), defining three grades of thinness corresponding to a BMI of 18.5, 17.0 and 16.0 kg/m2 at age 18 and ii) the WHO reference, defined here as three categories of thinness (-1, -2 and -3 SD of BMI for age) with the second and third named "thinness" and "severe thinness", respectively. RESULTS: : The prevalence of thinness was 21.4%, 6.4% and 2.0% based on the three IS cut-offs and 27.7%, 6.7% and 1.2% based on the WHO cut-offs. The prevalence of thinness categories tended to decrease according to age for both sexes for the IS reference and among girls for the WHO reference. CONCLUSION: The prevalence of the first category of thinness was larger with the WHO cut-offs than with the IS cut-offs while the prevalence of thinness of "grade 2" and thinness of "grade 3" (IS cut-offs) was similar to the prevalence of "thinness" and "severe thinness" (WHO cut-offs), respectively.

International consensus conference on PFAPA syndrome: evaluation of a new set of classification criteria

INTRODUCTION: PFAPA syndrome is characterized by periodic fever, associated with pharyngitis, cervical adenitis and/or aphthous stomatitis and belongs to the auto-inflammatory diseases. Diagnostic criteria are based on clinical features and the exclusion of other periodic fever syndromes. An analysis of a large cohort of patients has shown weaknesses for these criteria and there is a lack of international consensus. An International Conference was held in Morges in November 2008 to propose a new set of classification criteria based on a consensus among experts in the field.OBJECTIVE: We aimed to verify the applicability of the new set of classification criteria.PATIENTS & METHODS: 80 patients diagnosed with PFAPA syndrome from 3 centers (Genoa, Lausanne and Geneva) for pediatric rheumatology were included in the study. A detailed description of the clinical and laboratory features was obtained. The new classification criteria and the actual diagnostic criteria were applied to the patients.RESULTS: Only 40/80 patients (50%) fulfilled all criteria of the new classification. 31 patients were excluded because they didn't meet one of the 7 diagnostic criteria, 7 because of 2 criteria, and one because of 3 criteria. When we applied the current criteria to the same patients, 11/80 patients (13.7%) needed to be excluded. 8/80 patients (10%) were excluded from both sets. Exclusion was related only to some of the criteria. Number of patients for each not fulfilled criterion (new set of criteria/actual criteria): age (1/6), symptoms between episodes (2/2), delayed growth (4/1), main symptoms (21/0), periodicity, length of fever, interval between episodes, and length of disease (20/0). The application of some of the new criteria was not easy, as they were both very restrictive and needed precise information from the patients.CONCLUSION: Our work has shown that the new set of classification criteria can be applied to patients suspected for PFAPA syndrome, but it seems to be more restrictive than the actual diagnostic criteria. A further work of validation needs to be done in order to determine if this new set of classification criteria allow a good discrimination between PFAPA patients and other causes of recurrent fever syndromes.

Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.

As part of the ACuteTox project aimed at the development of non-animal testing strategies for predicting human acute oral toxicity, aggregating brain cell cultures (AGGR) were examined for their capability to detect organ-specific toxicity. Previous multicenter evaluations of in vitro cytotoxicity showed that some 20% of the tested chemicals exhibited significantly lower in vitro toxicity as expected from in vivo toxicity data. This was supposed to be due to toxicity at supracellular (organ or system) levels. To examine the capability of AGGR to alert for potential organ-specific toxicants, concentration-response studies were carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression levels of four selected genes. The lowest observed effect concentration (LOEC) determined for each chemical was compared with the IC20 reported for the 3T3/NRU cytotoxicity assay. A LOEC lower than IC20 by at least a factor of 5 was taken to alert for organ-specific toxicity. The results showed that the frequency of alerts increased with the level of toxicity observed in AGGR. Among the chemicals identified as alert were many compounds known for their organ-specific toxicity. These findings suggest that AGGR are suitable for the detection of organ-specific toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay, improve the predictive capacity of in vitro toxicity testing.