Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study

BACKGROUND: Data on the incidence of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected persons are sparse. It is controversial whether and how frequently HCV is transmitted by unprotected sexual intercourse. METHODS: We assessed the HCV seroprevalence and incidence of HCV infection in the Swiss HIV Cohort Study between 1988 and 2004. We investigated the association of HCV seroconversion with mode of HIV acquisition, sex, injection drug use (IDU), and constancy of condom use. Data on condom use or unsafe sexual behavior were prospectively collected between 2000 and 2004. RESULTS: The overall seroprevalence of HCV infection was 33% among a total of 7899 eligible participants and 90% among persons reporting IDU. We observed 104 HCV seroconversions among 3327 participants during a total follow-up time of 16,305 person-years, corresponding to an incidence of 0.64 cases per 100 person-years. The incidence among participants with a history of IDU was 7.4 cases per 100 person-years, compared with 0.23 cases per 100 person-years in patients without such a history (P<.001). In men who had sex with men (MSM) without a history of IDU who reported unsafe sex, the incidence was 0.7 cases per 100 person-years, compared with 0.2 cases per 100 person-years in those not reporting unsafe sex (P=.02), corresponding to an incidence rate ratio of 3.5 (95% confidence interval, 1.2-10.0). The hazard of acquiring HCV infection was elevated among younger participants who were MSM. CONCLUSIONS: HCV infection incidence in the Swiss HIV Cohort Study was mainly associated with IDU. In HIV-infected MSM, HCV infection was associated with unsafe sex.

Design, expression, and processing of epitomized hepatitis C virus-encoded CTL epitopes

Hepatitis C virus (HCV) vaccine efficacy may crucially depend on immunogen length and coverage of viral sequence diversity. However, covering a considerable proportion of the circulating viral sequence variants would likely require long immunogens, which for the conserved portions of the viral genome, would contain unnecessarily redundant sequence information. In this study, we present the design and in vitro performance analysis of a novel "epitome" approach that compresses frequent immune targets of the cellular immune response against HCV into a shorter immunogen sequence. Compression of immunological information is achieved by partial overlapping shared sequence motifs between individual epitopes. At the same time, sequence diversity coverage is provided by taking advantage of emerging cross-reactivity patterns among epitope variants so that epitope variants associated with the broadest variant cross-recognition are preferentially included. The processing and presentation analysis of specific epitopes included in such a compressed, in vitro-expressed HCV epitome indicated effective processing of a majority of tested epitopes, although re-presentation of some epitopes may require refined sequence design. Together, the present study establishes the epitome approach as a potential powerful tool for vaccine immunogen design, especially suitable for the induction of cellular immune responses against highly variable pathogens.

The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta

To study whether protein kinase C (PKC) isoforms can interact with protein-tyrosine-phosphatases (PTPs) which are connected to the insulin signaling pathway, we co-overexpressed PKC isoforms together with insulin receptor, docking proteins, and the PTPs SHP1 and SHP2 in human embryonic kidney (HEK) 293 cells. After phorbol ester induced activation of PKC isoforms alpha, beta 1, beta 2, and eta, we could show a defined gel mobility shift of SHP2, indicating phosphorylation on serine/threonine residues. This phosphorylation was not dependent on insulin receptor or insulin receptor substrate-1 (IRS-1) overexpression and did not occur for the closely related phosphatase SHP1. Furthermore, PKC phosphorylation of SHP2 was completely blocked by the PKC inhibitor bisindolylmaleimide and was not detectable when SHP2 was co-overexpressed with kinase negative mutants of PKC beta 1 and -beta 2. The phosphorylation also occurred on endogenous SHP2 in Chinese hamster ovary (CHO) cells stably overexpressing PKC beta 2. Using point mutants of SHP2, we identified serine residues 576 and 591 as phosphorylation sites for PKC. However, no change of phosphatase activity by TPA treatment was detected in an in vitro assay. In summary, SHP2 is phosphorylated on serine residues 576 and 591 by PKC isoforms alpha, beta 1, beta 2, and eta.

Elderly age is not a negative predictive factor for virological response to therapy with pegylated interferon-α and ribavirin in chronic hepatitis C virus patients

BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral therapy of chronic hepatitis C. However, elderly patients often show advanced fibrosis/cirrhosis as known negative predictive factor. The aim of this study was to assess age as an independent predictive factor during antiviral therapy. METHODS: Overall, 516 hepatitis C patients were treated with pegylated interferon-α and ribavirin, thereof 66 patients ≥60 years. We analysed the impact of host factors (age, gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors (genotype, viral load) on SVR per therapy course by performing a generalized estimating equations (GEE) regression modelling, a matched pair analysis and a classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9 and 26.1%, respectively, in young and elderly patients with hepatitis C virus (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4 and 84%. In the GEE model, age had no significant influence on achieving SVR. In matched pair analysis, SVR was not different in young and elderly patients (54.2 and 55.9% respectively; P = 0.795 in binominal test). In classification tree analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a significant predictive factor for achieving SVR, when relevant confounders are taken into account. As life expectancy in Western Europe at age 60 is more than 20 years, it is reasonable to treat chronic hepatitis C in selected elderly patients with relevant fibrosis or cirrhosis but without major concomitant diseases, as SVR improves survival and reduces carcinogenesis.

Relationship between Clostridium difficile toxin type and clinical features, severity and outcome in patients with C. difficile diarrhea (CDAD)

Background. Clostridium difficile infection is one of the major causes of antibiotic associated diarrhea and colitis in the United States. Currently, there is a dearth of literature on the risk factors and outcomes differences between the patients with infection due to the hypervirulent strain vs. the non-hypervirulent strains. The objective of this study was to determine the relationship between C. difficile toxin type and clinical features, severity and outcome in patients with C. difficile diarrhea. ^ Methods. The case group included 37 patients who had infections due to hypervirulent strain (tcdC deletion) and the control group included 55 patients with other toxin types (toxin A, B, binary toxin). A univariate analysis was performed followed by a multivariable logistic regression analysis to assess the differences between cases and controls. ^ Results. In the multivariate analyses, we found out that being a male was a protective factor for developing the infection due to the hypervirulent strain [OR 0.33; 95% CI 0.12-0.90]. Also, the hypervirulent group has worse clinical and economic outcomes, although the differences were small and nonsignificant. ^ Conclusions. There may likely be no predictive risk factor for acquiring infection due to the hypervirulent strain and the acquisition may be more linked to the infection control practices of the individual hospitals or location of patients. Hence, better infection control practices may prove helpful in decreasing the overall disease burden and thus improve patient outcomes. ^

La orientación en América Latina : Consideraciones generales acerca de los criterios de coherencia, cooperación y calidad

La Orientación en América Latina, como campo de formación profesional y en comparación con Europa y Estados Unidos, es una actividad de reciente aceptación en los medios académicos. La misma se ha caracterizado por una constante evolución en su afán de adaptarse a los nuevos cambios y transformaciones sociales, políticas y económicas que se suceden en el continente latinoamericano. En esta ponencia se presenta un panorama general acerca de la Orientación en América Latina. Las principales consideraciones formuladas se relacionan con cuatro dimensiones: a) la dimensión política pública, donde se presentan la situación actual y las propuestas al respecto; b) la dimensión contextual que hace referencia a la formación del orientador y los diferentes escenarios de acción; c) la dimensión organizacional que se relaciona con la provisión de este servicio, y d) la dimensión metodológica donde se desarrollan los principales aspectos relacionados con la práctica de la Orientación.

La orientación en América Latina : Consideraciones generales acerca de los criterios de coherencia, cooperación y calidad

La Orientación en América Latina, como campo de formación profesional y en comparación con Europa y Estados Unidos, es una actividad de reciente aceptación en los medios académicos. La misma se ha caracterizado por una constante evolución en su afán de adaptarse a los nuevos cambios y transformaciones sociales, políticas y económicas que se suceden en el continente latinoamericano. En esta ponencia se presenta un panorama general acerca de la Orientación en América Latina. Las principales consideraciones formuladas se relacionan con cuatro dimensiones: a) la dimensión política pública, donde se presentan la situación actual y las propuestas al respecto; b) la dimensión contextual que hace referencia a la formación del orientador y los diferentes escenarios de acción; c) la dimensión organizacional que se relaciona con la provisión de este servicio, y d) la dimensión metodológica donde se desarrollan los principales aspectos relacionados con la práctica de la Orientación.

La orientación en América Latina : Consideraciones generales acerca de los criterios de coherencia, cooperación y calidad

La Orientación en América Latina, como campo de formación profesional y en comparación con Europa y Estados Unidos, es una actividad de reciente aceptación en los medios académicos. La misma se ha caracterizado por una constante evolución en su afán de adaptarse a los nuevos cambios y transformaciones sociales, políticas y económicas que se suceden en el continente latinoamericano. En esta ponencia se presenta un panorama general acerca de la Orientación en América Latina. Las principales consideraciones formuladas se relacionan con cuatro dimensiones: a) la dimensión política pública, donde se presentan la situación actual y las propuestas al respecto; b) la dimensión contextual que hace referencia a la formación del orientador y los diferentes escenarios de acción; c) la dimensión organizacional que se relaciona con la provisión de este servicio, y d) la dimensión metodológica donde se desarrollan los principales aspectos relacionados con la práctica de la Orientación.

Two-way traveltimes of internal layers and ice thickness between Dome C - Vostok - Dome A

Chinese scientists will start to drill a deep ice core at Kunlun station near Dome A in the near future. Recent work has predicted that Dome A is a location where ice older than 1 million years can be found. We model flow, temperature and the age of the ice by applying a three-dimensional, thermomechanically coupled full-Stokes model to a 70 × 70 km**2 domain around Kunlun station, using isotropic non-linear rheology and different prescribed anisotropic ice fabrics that vary the evolution from isotropic to single maximum at 1/3 or 2/3 depths. The variation in fabric is about as important as the uncertainties in geothermal heat flux in determining the vertical advection which in consequence controls both the basal temperature and the age profile. We find strongly variable basal ages across the domain since the ice varies greatly in thickness, and any basal melting effectively removes very old ice in the deepest parts of the subglacial valleys. Comparison with dated radar isochrones in the upper one third of the ice sheet cannot sufficiently constrain the age of the deeper ice, with uncertainties as large as 500 000 years in the basal age. We also assess basal age and thermal state sensitivities to geothermal heat flux and surface conditions. Despite expectations of modest changes in surface height over a glacial cycle at Dome A, even small variations in the evolution of surface conditions cause large variation in basal conditions, which is consistent with basal accretion features seen in radar surveys.