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Risultati attesi Il progetto mira a individuare casi di HIV e sifilide riducendo la diffusione territoriale in contesti community based, tale attività prevede un indicatore di 1,5 utenti HIV+ individuato ogni 150 utenti secondo i parametri del Ministero della Salute, sebbene l’attività incida sul cambiamento di comportamento degli utenti attraverso un approccio continuativo alla diagnosi preventiva e alla condivisione di buone prassi di comportamento sessuale volte a ridurre lo stigma e i comportamenti a rischio di trasmissione di MST. L’attività inoltre prevede la definizione di un modello che potrà definire e instaurare un check point permanente nella Città di Torino come già esistente in altre realtà italiane (es. Bologna) o estere (es. Parigi, Barcellona, …). L’iniziativa testa la possibilità introdotta tra gli obiettivi definiti alla sigla del trattato di Parigi e dell’ASL quale impegno di città europea Fast Track City per la lotta all’HIV (https://www.fast-trackcities.org/). Pertanto il progetto mira altresì a garantire la presa in carico di soggetti HIV+, la continuità delle cure e la possibilità di combattere lo stigma verso le persone HIV+. Essendo all’interno di una progettualità definita da istituzione locale e regionale, in accordo con le principali realtà del Terzo Settore, troverà una continuità nel tempo. La valutazione dell’impatto sociale esaminerà la ricaduta in termini sociali ed economici definendo scientificamente l’utilità permanente del servizio stesso. Sistema di valutazione indicato nel progetto Gli indicatori valutativi del progetto sono dunque: numero di test HIV somministrati (sangue e saliva); numero di test sifilide somministrati; continuità del progetto e numero di utenti nell’arco temporale considerato; numero di utenti rilevati reattivi; numero di utenti che accedono al servizio sanitario regionale in caso di positività riscontrata. &nbsp

Transient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it is activated by cold temperatures and cooling compounds, such as menthol and icilin. Because of its role in cold allodynia, cold hyperalgesia and painful syndromes TRPM8 antagonists are currently being pursued as potential therapeutic agents for the treatment of pain hypersensitivity. Recently TRPM8 has been found in subsets of bladder sensory nerve fibres, providing an opportunity to understand and treat chronic hypersensitivity. However, most of the known TRPM8 inhibitors lack selectivity, and only three selective compounds have reached clinical trials to date. Here, we applied two virtual screening strategies to find new, clinics suitable, TRPM8 inhibitors. This strategy enabled us to identify naphthyl derivatives as a novel class of potent and selective TRPM8 inhibitors. Further characterization of the pharmacologic properties of the most potent compound identified, compound 1, confirmed that it is a selective, competitive antagonist inhibitor of TRPM8. Compound 1 also proved itself active in a overreactive bladder model in vivo. Thus, the novel naphthyl derivative compound identified here could be optimized for clinical treatment of pain hypersensitivity in bladder disorders but also in different other pathologies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

MMsINC (http://mms.dsfarm.unipd.it/MMsINC/search) is a database of non-redundant, richly annotated and biomedically relevant chemical structures. A primary goal of MMsINC is to guarantee the highest quality and the uniqueness of each entry. MMsINC then adds value to these entries by including the analysis of crucial chemical properties, such as ionization and tautomerization processes, and the in silico prediction of 24 important molecular properties in the biochemical profile of each structure. MMsINC is consequently a natural input for different chemoinformatics and virtual screening applications. In addition, MMsINC supports various types of queries, including substructure queries and the novel ‘molecular scissoring’ query. MMsINC is interfaced with other primary data collectors, such as PubChem, Protein Data Bank (PDB), the Food and Drug Administration database of approved drugs and ZINC.

Molecular docking represents an important technology for structure-based drug design. Docking is a computational technique aimed at the prediction of the most favorable ligand-target spatial configuration and an estimate of the corresponding complex free energy, although as stated at the beginning accurate scoring methods remain still elusive. In this chapter, the state of art of molecular docking methodologies and their applications in drug discovery is summarized.

Molecular docking represents an important technology for structure-based drug design. Docking is a computational technique aimed at the prediction of the most favorable ligand-target spatial configuration and an estimate of the corresponding complex free energy, although as stated at the beginning accurate scoring methods remain still elusive. In this chapter, the state of art of molecular docking methodologies and their applications in drug discovery is summarized.