Hybrid molecules targeting simultaneously DNA polymerase α (POLA1) and histone deacetylases (HDACs) were designed and synthesized to exploit a potential synergy of action. Among a library of screened molecules, MIR002 and GEM144 showed antiproliferative activity at nanomolar concentrations on a panel of human solid and haematological cancer cell lines. In vitro functional assays confirmed that these molecules inhibited POLA1 primer extension activity, as well as HDAC11.
View Article and Find Full Text PDFAtypical retinoids (AR) or retinoid-related molecules (RRMs) represent a promising class of antitumor compounds. Among AR, E-3-(3'-adamantan-1-yl-4'-hydroxybiphenyl-4-yl)acrylic acid (adarotene), has been extensively investigated. In the present work we report the results of our efforts to develop new adarotene-related atypical retinoids endowed also with POLA1 inhibitory activity.
View Article and Find Full Text PDFRescue personnel is at high risk for Post-traumatic Stress Disorder (PTSD) because of the possible repetitive exposition to "cruel details of traumatic events" (DSM-5). Literature reported PTSD rates in combat exposed veterans, although the Italian Navy military personnel has been frequently involved in no-war activities in most recent years, such as Search and Rescue (SAR) activities of civilians involved in catastrophic events. The study aimed at exploring the prevalence of PTSD and its impact on social and work functioning among divers of the Italian Navy employed in the SAR activities for the Costa Concordia shipwreck (2012), the collapsed control tower of the Genoa harbour (2013), and the "Mare Nostrum" and "Triton" immigrant emergency Operations in the Mediterranean Sea.
View Article and Find Full Text PDFObjective: The arm with the higher blood pressure (BP) is assigned as the follow up arm for hypertensive patients (reference-arm). We evaluated the reproducibility of this assignment.
Methods: BP was measured simultaneously on both arms with a double cuff validated device in two visits separated <10 days (two sets of three readings per visit).