Combined approach to hepatocellular carcinoma: a new treatment concept for nonresectable disease

Depending on tumor burden, hepatic function and patients' performance status, hepatocellular carcinoma is treated by surgery, local procedures, systemic therapy or palliation. The majority of patients are diagnosed at a stage where local therapy is the treatment of choice. Recently, the multikinase inhibitor sorafenib was found to improve the survival of patients with advanced hepatocellular carcinoma and conserved liver function. In this manuscript, we summarize the experimental evidence supporting the combination of a systemic targeted therapy with a local therapy. We also discuss the pros and cons of different schedules of combining such treatments. We conclude that there is enough of a theoretical argument to design clinical trials testing this strategy

Happy to breed in the city? : Urban food resources limit reproductive output in Western Jackdaws

Urban areas expand worldwide, transforming landscapes and creating new challenging habitats. Some bird species, mainly omnivorous feeding on human waste and cavity nesters, commonly breed in these habitats and are, therefore, regarded as urban-adapted. Although urban areas may provide new nesting sites and abundant human waste, the low breeding success found in some of these species suggests that the poor protein content in human waste might limit breeding parameters. We investigated whether the breeding success of a cavity nester and omnivorous species commonly breeding in urban areas, the Western Jackdaw (Corvus monedula), depended on the availability of good-quality non-urban food. We approached the objective by combining a literature review and experiments in the field. With the literature review, we compared jackdaw populations in different habitats across Europe and found that clutch size and number of fledglings per pair decreased with distance to non-urban foraging grounds, even after controlling for the effect of colony size, latitude, and climate. In two experiments, we tested whether the breeding success of urban pairs could be increased by supplementing high-quality food, first only during egg formation and second also until chick fledging. Food supplementation during egg formation led to larger eggs and higher hatching success than in urban control nests, but this did not result in higher chick survival. However, when food supplementation was prolonged until fledging in the second experiment, we observed a significant increase of nestling survival. These findings highlight that research and management actions should not only focus on species displaced by urbanization, but also on "urban-adapted" species, as they might be suffering from a mismatch between availability of nesting sites in buildings and adequate non-urban food resources. In these cases, nest sites should be provided in or close to adequate food resources.publishe

Diagnostic de la mort dans le contexte de la transplantation d'organes : directives médico-éthiques de l'Académie suisse des sciences médicales, approuvées par le Sénat de l'ASSM le 24 mai 2005

Le diagnostic de la mort repose sur l'interprétation de l'ensemble des informations issues de l'anamnèse, des résultats des examens complémentaires et sur la présence des signes cliniques de la défaillance du cerveau. Les directives définissent des critères cliniques et des examens techniques complémentaires qui permettent d'établir l'irréversibilité de la défaillance du cerveau. Ainsi, le diagnostic de la mort peut être établi avec certitude aussi bien dans les hôpitaux régionaux que dans les grands centres hospitaliers. Les présentes directives portent exclusivement sur le diagnostic de la mort. D'autres questions médico-éthiques, surtout celles qui concernent le don d'organes et l'arrêt de traitements vitaux, sont traitées dans les directives pour la transplantation d'organes et celles qui se rapportent aux problèmes éthiques survenant dans les soins intensifs

Mechanism for HIV-1 Tat Insertion into the Endosome Membrane*

The human immunodeficiency virus, type 1, transactivating protein Tat is a small protein that is strictly required for viral transcription and multiplication within infected cells. The infected cells actively secrete Tat using an unconventional secretion pathway. Extracellular Tat can affect different cell types and induce severe cell dysfunctions ranging from cell activation to cell death. To elicit most cell responses, Tat needs to reach the cell cytosol. To this end, Tat is endocytosed, and low endosomal pH will then trigger Tat translocation to the cytosol. Although this translocation step is critical for Tat cytosolic delivery, how Tat could interact with the endosome membrane is unknown, and the key residues involved in this interaction require identification. We found that, upon acidification below pH 6.0 (i.e. within the endosomal pH range), Tat inserts into model membranes such as monolayers or lipid vesicles. This insertion process relies on Tat single Trp, Trp-11, which is not needed for transactivation and could be replaced by another aromatic residue for membrane insertion. Nevertheless, Trp-11 is strictly required for translocation. Tat conformational changes induced by low pH involve a sensor made of its first acidic residue (Glu/Asp-2) and the end of its basic domain (residues 55–57). Mutation of one of these elements results in membrane insertion above pH 6.5. Tat basic domain is also required for efficient Tat endocytosis and membrane insertion. Together with the strict conservation of Tat Trp among different virus isolates, our results point to an important role for Tat-membrane interaction in the multiplication of human immunodeficiency virus type 1