Analysis of survival at cardiac arrest in events occurred in work environments in the territory served by an operations center of the 118 of Tuscany.

BACKGROUND: Every year in Italy and all around the world, cardiac arrest hits almost 1 person every 1000 people; a great deal of these events is likely to strike people outside their private houses. OBJECTIVES: Analyzing a cohort of cardiac arrest events occurred in various public- and work-places across a territorial area concerning an Emergency Unit related to the national emergency number (118) and assessing the efficacy of a first-aid intervention and the usage of a defibrillator while handling an acute cardiac event. METHODS: We analyzed data of 32 sanitary interventions on cardiac arrest events occurred from January 2015 to June 2018 across USL Toscana Centro - Pistoia and Empoli's territory. RESULTS: The acute cardiac event occurred in a "strictly speaking workplace" in 28.2% of cases, and in 18.7% during work activity. An AED was present for immediate cardiac arrest treatment in 15.6% of cases with a survival rate of 100% (n=5/5) (p=0.04); in 84.4% of cases the AED was available only after the arrival of national emergency rescuers and the relative survival rate was 40.74% (n=11/27). Regarding cardiopulmonary resuscitation, the survival rate appears to be higher (55.5% Vs 42.8%) when it was started by witnesses. CONCLUSIONS: The results of this study suggest that early defibrillation provided by work-related First Aid Emergency Procedure, may be a primary aid and a desirable standard to improve both workers' and private citizens' survival rate after cardiac arrest.

Expression of Pinopodes in the Endometrium from Recurrent Pregnancy Loss Women. Role of Thrombomodulin and Ezrin.

BACKGROUND: Pinopode expression has been suggested as a marker of endometrial receptivity. METHODS: We set up an experimental study comparing endometrial tissue from recurrent pregnancy loss (RPL, n = 30) and fertile control (CTR, n = 20) women in terms of pinopode expression/morphology; expression of thrombomodulin (TM) and ezrin; cytoskeletal organization. Endometrial samples were collected during implantation window and evaluated by scanning electron microscopy, western blot, and immunofluorescence. RESULTS: We found that RPL endometrial tissue showed: (i) increased pinopodes density (* p < 0.05); (ii) a reduced diameter of pinopodes (* p < 0.05); (iii) a decreased TM and ezrin expression (p < 0.05). Additionally, confocal images showed a significantly reduced expression of phosphorylated (p)-ezrin, confirming the results obtained through immunoblot analysis. Immunofluorescence staining showed that in CTR samples, junctions between cells are intact and clearly visible, whereas actin filaments appear completely lost in RPL endometrial samples; this suggests that, due to the impaired expression and activity of TM and ezrin, actin does not bind to plasma membrane in order to orchestrate the cytoskeletal actin filaments. CONCLUSIONS: Our findings suggest that an impaired expression of TM and expression/activation of ezrin may affect the connection between the TM and actin cytoskeleton, impairing the organization of cytoskeleton and, eventually, the adequate pinopode development.

In vitro characterization, ADME analysis, and histological and toxicological evaluation of BM1, a macrocyclic amidinourea active against azole-resistant Candida strains.

BACKGROUND: Candida species are one of the most common causes of nosocomial bloodstream infections among the opportunistic fungi. Extensive use of antifungal agents, most of which were launched on the market more than 20 years ago, led to the selection of drug-resistant or even multidrug-resistant fungi. We recently described a novel class of antifungal macrocyclic compounds with an amidinourea moiety that is highly active against azole-resistant Candida strains. OBJECTIVE: A compound from this family, BM1, was investigated in terms of in vitro activity against various Candida species, including C. auris isolates, interaction with the ABC transporter, CDR6, and in vivo distribution and safety. METHODS: In vitro assays (CYP inhibition, microsomal stability, permeability, spot assays) were used to collect chemical and biological data; animal models (rat) paired with LC-MS analysis were utilised to evaluate in vivo toxicology, pharmacokinetics, and distribution. RESULTS: The current research shows BM1 has a low in vivo toxicity profile, affinity for the renal system in rats, and good absorption, distribution, metabolism, and excretion (ADME). BM1 also has potent activity against azole-resistant fungal strains, including C. auris isolates and CDR6-overexpressing strains. CONCLUSIONS: The results confirmed low minimum inhibitory concentrations (MICs) against several Candida species, including preliminary data vs. C. auris. BM1 has good ADME and biochemical characteristics, is suitable and safe for daily administration and is particularly indicated for renal infections. These data indicate BM1 and its derivatives form a novel, promising antifungal class.