Pilot Study for a Model for the Collection of Waiting Lists Data.

The analysis of data on waiting lists in Italy is regulated by the PNGLA (National Plan for the Governance of Waiting Lists). However, the Plan does not specify the characteristics of the data to be returned by the Regions for the purposes of monitoring, with the result that it is frequently either in aggregate form, unreadable, or incomplete, and therefore cannot be analysed in any meaningful way. Fondazione the Bridge and AGENAS, with the University of Genoa and the University of Pavia, conducted a pilot study on a methodological model for the collection of waiting lists data. The model proved to be effective and replicable, also providing a more valuable opportunity to analyse waiting lists data.

Outlining the Orientation Toward Socially Relevant Issues in Competitive R&D Funding Instruments.

While project-based funding in public R&D investments has grown in importance in all European countries over the last two decades, there is widespread concern among decision-makers about the actual orientation of project funding instruments to promote societal well-being. The capability of public R&D investment to improve the quality of citizens' lives implies the pursuit of "relevant" social objectives related to existing or emerging problems affecting individuals' lives and society. Particularly, when referring to project-funded research, the question of "relevance" in research objectives recalls the never-ending debate over how to translate policymakers' request for producing value from public investments in research activities into "usable results". The manuscript explores, using recent data collected at European level on public R&D funding, the portfolio of research project funding policy instruments of various public research funding organizations (RFOs) in order to shed light on how and to what extent it is oriented to address socially relevant issues. The authors examine the characterization of the single project funding instruments, which are intended to incorporate the motivations and targeted goals of public action, and the RFOs that manage them. They specifically assume that the actual orientation of funding instruments, beyond the declared objectives, is influenced by some features related to their implementation operated by the RFOs, such as the importance given to specific evaluation criteria and the composition of the evaluation panels in the selection process of the funding beneficiaries.

Use of molecular simulation for mapping conformational CYP2E1 epitopes.

The identification of the epitopes recognized by autoantibodies against cytochrome P450s (CYPs) associated with drug-induced hepatotoxicity is difficult because of their conformational nature. In the present investigation, we used a novel approach based on the analysis of the whole molecule antigenic capacity following single amino acid substitutions to identify the conformational epitopes on CYP2E1. A molecular model of CYP2E1 was generated based on the CYP2C5 crystal structure, and potential motifs for amino acid exchanges were selected by computer simulation in the surface of alpha helices and beta sheets. Fourteen modified, apparently correctly folded CYP2E1 variants were produced in Escherichia coli and evaluated in immunoprecipitation experiments using sera with anti-CYP2E1 autoreactivity from 10 patients with halothane hepatitis and 12 patients with alcoholic liver disease. Ala substitution of Glu-248 and Lys-251 as well as of Lys-324, Lys-342, Lys-420, and Phe-421 severely decreased or abolished CYP2E1 recognition by the majority of both the halothane hepatitis and alcoholic liver disease sera, whereas the other substitutions had only minor effects. Based on the structural model, these substitutions identified two distinct epitopes on the CYP2E1 surface corresponding to the G-helix and an area formed by juxtaposition of the J' and K'' helices, respectively. The combined use of molecular modeling and single amino acid mutagenesis is thus a useful approach for the characterization of conformational epitopes recognized by autoantibodies.

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C.

The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as markers of oxidative stress in 145 CHC patients with different alcohol consumption, 20 HCV-free heavy drinkers (HD) without liver disease, and 50 healthy controls. Anti-MDA IgG was increased in CHC patients irrespective of alcohol intake as well as in the HD group. CHC patients with moderate alcohol intake (<50 g ethanol/d), but not HD, also had significantly higher values of anti-AAHP-HSA, anti-HNE-HSA, and anti-Ox-CL IgG (P <.05) than controls. A further elevation (P <.001) of these antibodies was evident in CHC patients with heavy alcohol intake (>50 g ethanol/d). Anti-AAHP and anti-Ox-CL IgG above the 95th percentile in the controls were observed in 24% to 26% of moderate and 58% to 63% of heavy drinkers but only in 6% to 9% of the abstainers. The risk of developing oxidative stress during CHC was increased 3-fold by moderate and 13- to 24-fold by heavy alcohol consumption. Heavy drinking CHC patients had significantly more piecemeal necrosis and fibrosis than abstainers. Diffuse piecemeal necrosis was 4-fold more frequent among alcohol-consuming patients with lipid peroxidation-related antibodies than among those without these antibodies. In conclusion, even moderate alcohol consumption promotes oxidative stress in CHC patients, suggesting a role for oxidative injury in the worsening of CHC evolution by alcohol.