629 research outputs found

    More on donor-derived T-cell leukemia after bone marrow transplantation

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    http://www.nejm.org/doi/full/10.1056/NEJMc06105

    How Current Direct-Acting Antiviral and Novel Cell Culture Systems for HCV are Shaping Therapy and Molecular Diagnosis of Chronic HCV Infection

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    We have entered a new era of hepatitis C virus (HCV) therapy in which elimination of infection and disease is a real possibility. HCV cell culture models were instrumental for identification of therapeutic targets, testing candidate drugs, and profiling of therapeutic strategies. Here we describe current and novel methods of cell culture systems for HCV that are allowing investigation of HCV life cycle and virus-host interaction required for replication and propagation. The development of protocols to grow infectious virus in culture and generate hepatocyte cell lines from specific individuals hold great promise to investigate the mechanisms exploited by the virus to spread the infection and the host factors critical for HCV replication and propagation, or resistance to infection. Since host factors are presumably conserved and equally interacting with different HCV isolates and genotypes, the development of drugs targeting host factors essential for virus replication holds great promises in further increasing treatment efficacy. Refocusing of therapeutic goals also impacted in vitro diagnosis. The primary goal of anti-HCV therapy is to achieve a sustained virologic response (SVR) defined as " undetectable" HCV RNA genome in the serum or plasma at 12 to 24 weeks following the end of treatment. Use of direct antiviral agents has substantially changed the threshold of the viral load used to define SVR and led to a reassessment, as discussed herein, of result interpretation and requirements of clinically-approved, quantitative molecular assays

    Modified Hemagglutination Tests for COVID-19 Serology in Resource-Poor Settings: Ready for Prime-Time?

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    During the ongoing COVID-19 pandemic, serology has suffered several manufacturing and budget bottlenecks. Kode technology exposes exogenous antigens on the surface of cells; in the case of red blood cells, modified cells are called kodecytes, making antibody\u2013antigen reactions detectable by the old-fashioned hemagglutination test. In this commentary, we review evidence supporting the utility of SARS-CoV-2 Spike kodecytes for clinical diagnostic purposes and serosurveys in resource-poor settings

    Current factor IX replacement options for hemophilia B and the challenges ahead

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    Introduction: Therapy for hemophilia B is aimed at replacing the congenital deficiency of coagulation factor IX (FIX). For replacement therapy, several FIX concentrates derived from donated human plasma or engineered by recombinant DNA technology are currently commercially available. The use of these products is well established and permit patients a relatively normal life. To further improve treatment efficacy, recombinant FIX products with a prolonged half-life have been developed, allowing relaxed prophylactic dosing and reducing treatment burden. Areas covered: In this review, we explore the current FIX replacement options for hemophilia B patients by analyzing the outcomes of their main clinical trials. We cover advances in the FIX molecules with extended half-life (EHL). Published literature on products for replacement of hemophilia B was retrieved using PubMed with no temporal limits. Expert opinion: The recent introduction of recombinant EHL FIX products has represented a major advance in the therapeutic management of hemophilia B patients, permitting both a reduction of treatment burden and improving patients' compliance to prophylaxis and, ultimately, quality of life

    Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

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    Sterilizing immunity after vaccination is desirable to prevent the spread of infection from vaccinees, which can be especially dangerous in hospital settings while managing frail patients. Sterilizing immunity requires neutralizing antibodies at the site of infection, which for respiratory viruses such as SARS-CoV-2 implies the occurrence of neutralizing IgA in mucosal secretions. Systemic vaccination by intramuscular delivery induces no or low-titer neutralizing IgA against vaccine antigens. Mucosal priming or boosting, is needed to provide sterilizing immunity. On the other side of the coin, sterilizing immunity, by zeroing interhuman transmission, could confine SARS-CoV-2 in animal reservoirs, preventing spontaneous attenuation of virulence in humans as presumably happened with the endemic coronaviruses. We review here the pros and cons of each vaccination strategy, the current mucosal SARS-CoV-2 vaccines under development, and their implications for public health

    Recensione a David Fontanesi, Preludi ad una metafisica della musica contemporanea

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    Preludi ad una metafisica della musica contemporanea, scritto dal compositore David Fontanesi e da poco pubblicato dalla Zecchini, è un breve ma assai intenso testo destinato a far discutere per la radicalità delle posizioni che l’Autore strenuamente difende. Il libro è infatti un vero e proprio atto d’accusa verso una disumanizzazione della musica del Ventesimo secolo, accusa che non di rado prende la forma dell’invettiva, ora veemente ora sarcastica, senza tuttavia che ciò sminuisca l’apparato critico e teoretico. L’Autore supporta i suoi sferzanti giudizi estetici con puntuali analisi delle partiture, che fanno eco a un’indagine di ordine metafisico, volta cioè a enucleare i presupposti concettuali delle teorie compositive che hanno segnato una svolta nella prassi tanto produttiva quanto ricettiva della musica moderna-contemporanea

    Il ruolo del confronto nella critica artistica

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    The topic of this paper is comparison and classification among artworks. In the first section, I underline the importance of comparison in art criticism, as acknowledged by contemporary philosophers such as Sibley, Vaida and D’Angelo. In the second section, I analyze the nature of comparison as treated by Eighteen century British empiricists such as Hume and Gerard, who recognized, implicitly or explicitly, the existence of two levels of comparison, one involving sensibility and the other relying on reasoning and leading to classification among artworks and species of beauty. In the third and last chapter, I return to the recent analytical debate (Pratt, Vermazen, Dickie and Carroll) and establish both the limits of classification and the real point of comparison, which amounts to refine our taste and achieve a deeper understanding of artworks

    Tweaking Mesenchymal Stem/Progenitor Cell Immunomodulatory Properties with Viral Vectors Delivering Cytokines

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    Mesenchymal Stem Cells (MSCs) can be found in various body sites. Their main role is to differentiate into cartilage, bone, muscle, and fat cells to allow tissue maintenance and repair. During inflammation, MSCs exhibit important immunomodulatory properties that are not constitutive, but require activation, upon which they may exert immunosuppressive functions. MSCs are defined as "sensors of inflammation" since they modulate their ability of interfering with the immune system both in vitro and in vivo upon interaction with different factors. MSCs may influence immune responses through different mechanisms, such as direct cell-to-cell contact, release of soluble factors, and through the induction of anergy and apoptosis. Human MSCs are defined as plastic-adherent cells expressing specific surface molecules. Lack of MHC class II antigens makes them appealing as allogeneic tools for the therapy of both autoimmune diseases and cancer. MSC therapeutic potential could be highly enhanced by the expression of exogenous cytokines provided by transduction with viral vectors. In this review, we attempt to summarize the results of a great number of in vitro and in vivo studies aimed at improving the ability of MSCs as immunomodulators in the therapy of autoimmune, degenerative diseases and cancer. We will also compare results obtained with different vectors to deliver heterologous genes to these cells
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