Imaging di risonanza magnetica nucleare nello studio del tumore della prostata

Aim of the present study was to evaluate the accuracy of transrectal ultrasound biopsy (TRUS-biopsy) directed to regions with abnormal MRI and/or MRSI (magnetic resonance spectroscopic imaging ) for both the transition (TZ) and the peripheral (PZ) zones in patients who presented with persistent suspect for prostate cancer and with prior negative biopsy. We also evaluated relationship between MRSI results and histopathological findings of biopsy. 54 patients with the aforementioned characteristics underwent MRI/MRSI at least 6 months after prior negative biopsy; interval between MRI/3D-MRSI and the further TRUS-biopsy was less than 3 months. The prostate was divided in 12 regions both for imaging interpretation and biopsy. Moreover one to three cores more were taken from each region with abnormal MRI and/or 3D-MRSI. Twenty-two out of 54 patients presented cancer at MRI/MRSI-directed-TRUS-biopsy. On a patient basis the highest accuracy was obtained by assigning malignancy on a positive finding with MRSI and MRI even though it was not significantly greater than that obtained using MRI alone (area under the ROC curve, AUC: 0.723 vs. 0.676). On a region (n=648) basis the best accuracy was also obtained by considering positive both MRSI and MRI for PZ (0.768) and TZ (0.822). Twenty-eight per cent of cores with prostatitis were false positive findings on MRSI, whereas only 2.7% of benign prostatic hyperplasia was false positive. In conclusion the accuracy of MRI/MRSI-directed biopsies in localization of prostate cancer is good in patient and region analyses. The combination of both MRI and MRSI results makes TRUS-biopsy more accurate particularly in the TZ (0.822) for patients with prior negative biopsies. Histopathological analysis showed that the main limitation of MRSI is the percentage of false positive findings due to prostatitis.

Sorveglianza dell'influenza aviare: studio di un sistema di rilevazione precoce della circolazione virale in popolazioni di volatili selvatici

The emergency of infection by highly pathogenic avian influenza virus (HPAI) subtype H5N1 has focused the attention of the world scientific community, requiring the prompt provision of effective control systems for early detection of the circulation of low pathogenic influenza H5 viruses (LPAI) in populations of wild birds to prevent outbreaks of highly pathogenic (HPAI) in populations of domestic birds with possible transmission to humans. The project stems from the aim to provide, through a preliminary analysis of data obtained from surveillance in Italy and Europe, a preliminary study about the virus detection rates and the development of mathematical models, an objective assessment of the effectiveness of avian influenza surveillance systems in wild bird populations, and to point out guidelines to support the planning process of the sampling activities. The results obtained from the statistical processing quantify the sampling effort in terms of time and sample size required, and simulating different epidemiological scenarios identify active surveillance as the most suitable for endemic LPAI infection monitoring in wild waterfowl, and passive surveillance as the only really effective tool in early detecting HPAI H5N1 circulation in wild populations. Given the lack of relevant information on H5N1 epidemiology, and the actual finantial and logistic constraints, an approach that makes use of statistical tools to evaluate and predict monitoring activities effectiveness proves to be of primary importance to direct decision-making and make the best use of available resources.

Rapporto tra struttura e funzione della cistatina B e dei suoi mutanti in relazione all'epilessia mioclonica progressiva di tipo 1 (EPM1)

This work shows for the first time that native CSTB polymerizes on addition of Cu2+ and DnaK (Hsp70). Cysteines are involved in the polymerization process and in particular at least one cysteine is necessary. We propose that Cu2+ interacts with the thiol group of cysteine and oxidize it. The oxidized cysteine modifies the CSTB structure allowing interaction with DnaK/Hsp70 to occur. Thus, Cu2+ binding to CSTB exposes a site for DnaK and such interaction allows the polymerization of CSTB. The polymers generated from native CSTB monomers, are DTT sensitive and they may represent physiological polymers. Denatured CSTB does not require Cu2+ and polymerizes simply on addition of DnaK. The polymers generated from denatured CSTB do not respond to DTT. They have characteristics similar to those of the CSTB toxic aggregates described in vivo in eukaryotic cells following CSTB over-expression. Interaction between CSTB and Hsp70 is shown by IP experiments. The interaction occurs with WT CSTB and not with the cys mutant. This suggests that disulphur bonds are involved. Methal-cathalyzed oxidation of proteins involves reduction of the metal ion(s) bound to the protein itself and oxidation of neighboring ammino acid residues resulting in structural modification and de-stabilization of the molecule. In this work we propose that the cysteine thyol residue of CSTB in the presence of Cu2+ is oxidized, and cathalyzes the formation of disulphide bonds with Hsp70, that, once bound to CSTB, mediates its polymerization. In vivo this molecular mechanism of CSTB polymerization could be regulated by redox environment through the cysteine residue. This may imply that CSTB physiological polymers have a specific cellular function, different from that of the protease inhibitor known for the CSTB monomer. This hypothesis is interesting in relation to Progressive Myoclonus Epilepsy of type 1 (EPM1). This pathology is usually caused by mutations in the CSTB gene. CSTB is a ubiquitous protein, but EPM1 patients have problems only in the central nervous system. Maybe physiological CSTB polymers have a specific function altered in people affected by EPM1.

Libro, diaspora e ri-costruzioni identitarie. Per una storia della tipografia sefardita portoghese nell'Italia del Cinquecento

Il lavoro ripercorre le tracce che gli ebrei portoghesi, esuli dopo il biennio 1496-97, lasciarono nel loro cammino attraverso l'Europa. In particolare, l'interesse si concentra sulla breve parentesi italiana, che grazie all'apertura e alla disponibilità  di alcuni Signori, come i Gonzaga di Mantova, i Medici, i Dogi della Serenissima e gli Este, risulta ricchissima di avvenimenti e personaggi, decisivi anche per la storia culturale del Portogallo. L'analisi parte evidenziando l'importanza che ebbe la tipografia ebraica in Portogallo all'epoca della sua introduzione nel Paese; in secondo luogo ripercorre la strada che, dal biennio del primo decreto di espulsione e del conseguente battesimo di massa, porta alla nascita dell'€™Inquisizione in Portogallo. Il secondo capitolo tenta di fare una ricostruzione, il più possibile completa e coerente, dei movimenti degli esuli, bollati come marrani e legati alle due maggiori famiglie, i Mendes e i Bemveniste, delineando poi il primo nucleo di quella che diventerà  nel Seicento la comunità  sefardita portoghese di Amsterdam, dove nasceranno le personalità  dissidenti di Uriel da Costa e del suo allievo Spinoza. Il terzo capitolo introduce il tema delle opere letterarie, effettuando una rassegna dei maggiori volumi editi dalle officine tipografiche ebraiche stanziatesi in Italia fra il 1551 e il 1558, in modo particolare concentrando l'attenzione sull'€™attività  della tipografia Usque, da cui usciranno numerosi testi di precettistica in lingua ebraica, ma soprattutto opere cruciali come la famosa «Bibbia Ferrarese» in castigliano, la «Consolação às Tribulações de Israel», di Samuel Usque e la raccolta composta dal romanzo cavalleresco «Menina e Moça» di Bernardim Ribeiro e dall'ecloga «Crisfal», di un autore ancora non accertato. L'ultimo capitolo, infine, si propone di operare una disamina di queste ultime tre opere, ritenute fondamentali per ricostruire il contesto letterario e culturale in cui la comunità  giudaica in esilio agiva e proiettava le proprie speranze di futuro. Per quanto le opere appartengano a generi diversi e mostrino diverso carattere, l'€™ipotesi è che siano parte di un unicum filosofico e spirituale, che intendeva sostanzialmente indicare ai confratelli sparsi per l'Europa la direzione da prendere, fornendo un sostegno teoretico, psicologico ed emotivo nelle difficili condizioni di sopravvivenza, soprattutto dell'integrità religiosa, di ciascun membro della comunità.