Castanea sativa Mill. Bark Extract Protects U-373 MG Cells and Rat Brain Slices Against Ischemia and Reperfusion Injury

Ischemic brain injury is one of the most important causes of death worldwide. The use of one-drug-multi-target agents based on natural compounds is a promising therapeutic option for cerebral ischemia due to their pleiotropic properties. This study assessed the neuroprotective properties of Castanea sativa Mill. bark extract (ENC) in human astrocytoma U-373 MG cells subjected to oxygen-glucose deprivation and reperfusion and rat cortical slices subjected to ischemia-like conditions or treated with glutamate or hydrogen peroxide. Neuroprotective effects were determined by assessing cells or slices viability (MTT assay), ROS formation (DCFH-DA assay), apoptosis (sub G0/G1 peak), nuclear fragmentation and chromatin condensation (DAPI staining) as well as changes in lysosomes and mitochondria morphology (Acridine Orange and Rhodamine123 staining, respectively). ENC treatment before injury on U-373 MG cells (5-50 µg/ml) and cortical slices (50-100 µg/ml) provided neuroprotection, while lower or higher concentrations (100 µg/ml U-373 MG cells, 200 µg/ml brain slices) were ineffective.. ENC addition during reperfusion or after the injury was not found to be effective. The results suggest that ENC might hold potential as preventive neuroprotective agent, and indicate the importance of further studies exploring its mechanism of action. This article is protected by copyright. All rights reserved. © 2016 Wiley Periodicals, Inc

Measurement of the form factors of charged kaon semileptonic decays

International audienceA measurement of the form factors of charged kaon semileptonic decays is presented, based on 4.4 × 10$^{6}$K$^{±}$ → π$^{0}$e$^{±}$ν$_{e}$ (K$_{e3}^{±}$ ) and 2.3 × 10$^{6}$K$^{±}$ → π$^{0}$μ±ν$_{μ}$ (K$_{μ3}^{±}$ ) decays collected in 2004 by the NA48/2 experiment. The results are obtained with improved precision as compared to earlier measurements. The combination of measurements in the K$_{e3}^{±}$ and K$_{μ3}^{±}$ modes is also presented

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

The NA48/2 experiment at CERN reports the first observation of the $K^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu$ decay based on a sample of 2437 candidates with 15% background contamination collected in 2003-2004. The decay branching ratio in the kinematic region of the squared dilepton mass above $0.03$~GeV$^2/c^4$ is measured to be $(0.65 \pm 0.03) \times 10^{-6}$. The extrapolation to the full kinematic space, using a specific model, is found to be $(3.45 \pm 0.17) \times 10^{-6}$, in agreement with chiral perturbation theory predictions

First observation and study of the K±→π0π0μ±νK^{\pm} \rightarrow \pi^{0} \pi^{0} \mu^{\pm} \nu decay

International audienceThe NA48/2 experiment at CERN reports the first observation of the K$^{±}$ → π$^{0}$π$^{0}$μ$^{±}$ν decay based on a sample of 2437 candidates with 15% background contamination collected in 2003–2004. The decay branching ratio in the kinematic region of the squared dilepton mass above 0.03 GeV$^{2}$/c$^{4}$ is measured to be (0.65 ± 0.03) × 10$^{−6}$. The extrapolation to the full kinematic space, using a specific model, is found to be (3.45 ± 0.16) × 10$^{−6}$, in agreement with chiral perturbation theory predictions

Recommendations for self-monitoring in pediatric diabetes: A consensus statement by the ISPED

none165noScaramuzza, Andrea; Cherubini, Valentino; Tumini, Stefano; Bonfanti, Riccardo; Buono, Pietro; Cardella, Francesca; D’Annunzio, Giuseppe; Frongia, Anna Paola; Lombardo, Fortunato; Monciotti, Anna Carla Maria; Rabbone, Ivana; Schiaffini, Riccardo; Toni, Sonia; Zucchini, Stefano; Frontino, Giulio; Iafusco, Dario; Arnaldi, Claudia; Banin, Patrizia; Barbetti, Fabrizio; Beccaria, Luciano; Benelli, Marzia; Berardi, Rosario; Biagioni, Martina; Bianchi, Giuliana; Bizzarri, Carla; Blasetti, Annalisa; Bobbio, Adriana; Boccato, Stefano; Bontempi, Franco; Bruzzese, Mariella; Cadario, Francesco; Calcaterra, Valeria; Cannatà, Alessandra; Cappa, Marco; Cardani, Roberta; Cardinale, Giuliana Marcella; Carloni, Ines; Castaldo, Vincenzo; Cauvin, Vittoria; Cerutti, Franco; Cester, Anna Maria; Chessa, Margherita; Chiarelli, Francesco; Chiari, Giovanni; Chiumello, Giuseppe; Cicchetti, Mario; Cirillo, Dante; Citriniti, Felice; Citro, Giuseppe; Coccioli, Maria Susanna; Cotellessa, Mario; Crinò, Antonino; De Berardinis, Fiorella; De Filippo, Gianpaolo; De Giorgi, Giovanni; De Luca, Filippo; De Marco, Rosaria; Delvecchio, Maurizio; Faleschini, Elena; Federico, Giovanni; Fifi, Anna Rita; Fontana, Franco; Franzese, Adriana; Frezza, Elda; Frongia, Annapaola; Gaiero, Alberto; Galderisi, Alfonso; Gallo, Francesco; Gargantini, Luigi; Ghione, Silvia; Giorgetti, Chiara; Gualtieri, Antonella; Guasti, Monica; Guerraggio, Lucia; Iannilli, Antonio; Ingletto, Dario; Iossa, Carmine; Iovene, Brunella; Iughetti, Lorenzo; Kaufmann, Peter; La Loggia, Alfonso; Lazzaro, Nicola; Lenzi, Lorenzo; Lera, Riccardo; Lia, Rosanna; Lo Presti, Donatella; Lorini, Renata; Lucchesi, Sonia; Luceri, Sergio; Madeo, Simona Filomena; Maffeis, Claudio; Mainetti, Benedetta; Mammi, Francesco; Manca Bitti, Maria Luisa; Marigliano, Marco; Marinari, Alessandra; Marinaro, Anna Maria; Meloni, Gianfranco; Marsciani, Alberto; Mastrangelo, Lisa; Mastrangelo, Costanzo; Meschi, Franco; Minasi, Domenico; Minenna, Adelaide; Minuto, Nicola; Monciotti, Carlamaria; Morganti, Gianfranco; Mozzillo, Enza; Nugnes, Rosa; Paradiso, Emanuela; Pardi, Daniela; Pasquino, Bruno; Patrizia Patera, Ippolita; Pennati, Cristina; Pepe, Rossella; Piccini, Barbara; Perrotta, Angelo; Piccinno, Elvira; Pinelli, Leonardo; Piredda, Gavina; Pocecco, Mauro; Ponzi, Giuseppe; Prandi, Elena; Predieri, Barbara; Prisco, Francesco; Quinci, Maria; Ricciardi, Maria Rossella; Rigamonti, Andrea; Ripoli, Carlo; Sabbion, Alberto; Salardi, Silvana; Salvatoni, Alessandro; Salvo, Caterina; Salzano, Giuseppina; Saporiti, Anna; Sardi, Rita; Schieven, Eleonardo; Scipione, Mirella; Soci, Cristina; Soro, Miriam; Spallino, Luisa; Stamati, Filomena; Suprani, Tosca; Savastio, Silvia; Taccardi, Rosa Anna; Tarchini, Luis; Tomaselli, Letizia; Tonini, Giorgio; Torelli, Cataldo; Tornese, Gianluca; Trada, Michela; Valerio, Giuliana; Vanelli, Maurizio; Vanini, Roberto; Vascotto, Marina; Vergerio, Amedeo; Viscardi, Matteo; Zaffani, Silvana; Zampolli, Maria; Zanatta, Manuela; Zanette, Giorgio; Zanfardino, Angela; Zecchino, Clara; Zedda, Maria Antonietta; Zuccotti, Gian VincenzoScaramuzza, Andrea; Cherubini, Valentino; Tumini, Stefano; Bonfanti, Riccardo; Buono, Pietro; Cardella, Francesca; D’Annunzio, Giuseppe; Frongia, Anna Paola; Lombardo, Fortunato; Monciotti, Anna Carla Maria; Rabbone, Ivana; Schiaffini, Riccardo; Toni, Sonia; Zucchini, Stefano; Frontino, Giulio; Iafusco, Dario; Arnaldi, Claudia; Banin, Patrizia; Barbetti, Fabrizio; Beccaria, Luciano; Benelli, Marzia; Berardi, Rossana; Biagioni, Martina; Bianchi, Giuliana; Bizzarri, Carla; Blasetti, Annalisa; Bobbio, Adriana; Boccato, Stefano; Bontempi, Franco; Bruzzese, Mariella; Cadario, Francesco; Calcaterra, Valeria; Cannatà, Alessandra; Cappa, Marco; Cardani, Roberta; Cardinale, Giuliana Marcella; Carloni, Ines; Castaldo, Vincenzo; Cauvin, Vittoria; Cerutti, Franco; Cester, Anna Maria; Chessa, Margherita; Chiarelli, Francesco; Chiari, Giovanni; Chiumello, Giuseppe; Cicchetti, Mario; Cirillo, Dante; Citriniti, Felice; Citro, Giuseppe; Coccioli, Maria Susanna; Cotellessa, Mario; Crinò, Antonino; De Berardinis, Fiorella; De Filippo, Gianpaolo; De Giorgi, Giovanni; De Luca, Filippo; De Marco, Rosaria; Delvecchio, Maurizio; Faleschini, Elena; Federico, Giovanni; Fifi, Anna Rita; Fontana, Franco; Franzese, Adriana; Frezza, Elda; Frongia, Annapaola; Gaiero, Alberto; Galderisi, Alfonso; Gallo, Francesco; Gargantini, Luigi; Ghione, Silvia; Giorgetti, Chiara; Gualtieri, Antonella; Guasti, Monica; Guerraggio, Lucia; Iannilli, Antonio; Ingletto, Dario; Iossa, Carmine; Iovene, Brunella; Iughetti, Lorenzo; Kaufmann, Peter; La Loggia, Alfonso; Lazzaro, Nicola; Lenzi, Lorenzo; Lera, Riccardo; Lia, Rosanna; Lo Presti, Donatella; Lorini, Renata; Lucchesi, Sonia; Luceri, Sergio; Madeo, Simona Filomena; Maffeis, Claudio; Mainetti, Benedetta; Mammi, Francesco; Manca Bitti, Maria Luisa; Marigliano, Marco; Marinari, Alessandra; Marinaro, Anna Maria; Meloni, Gianfranco; Marsciani, Alberto; Mastrangelo, Lisa; Mastrangelo, Costanzo; Meschi, Franco; Minasi, Domenico; Minenna, Adelaide; Minuto, Nicola; Monciotti, Carlamaria; Morganti, Gianfranco; Mozzillo, Enza; Nugnes, Rosa; Paradiso, Emanuela; Pardi, Daniela; Pasquino, Bruno; Patrizia Patera, Ippolita; Pennati, Cristina; Pepe, Rossella; Piccini, Barbara; Perrotta, Angelo; Piccinno, Elvira; Pinelli, Leonardo; Piredda, Gavina; Pocecco, Mauro; Ponzi, Giuseppe; Prandi, Elena; Predieri, Barbara; Prisco, Francesco; Quinci, Maria; Ricciardi, Maria Rossella; Rigamonti, Andrea; Ripoli, Carlo; Sabbion, Alberto; Salardi, Silvana; Salvatoni, Alessandro; Salvo, Caterina; Salzano, Giuseppina; Saporiti, Anna; Sardi, Rita; Schieven, Eleonardo; Scipione, Mirella; Soci, Cristina; Soro, Miriam; Spallino, Luisa; Stamati, Filomena; Suprani, Tosca; Savastio, Silvia; Taccardi, Rosa Anna; Tarchini, Luis; Tomaselli, Letizia; Tonini, Giorgio; Torelli, Cataldo; Tornese, Gianluca; Trada, Michela; Valerio, Giuliana; Vanelli, Maurizio; Vanini, Roberto; Vascotto, Marina; Vergerio, Amedeo; Viscardi, Matteo; Zaffani, Silvana; Zampolli, Maria; Zanatta, Manuela; Zanette, Giorgio; Zanfardino, Angela; Zecchino, Clara; Zedda, Maria Antonietta; Zuccotti, Gian Vincenz

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy

Background The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population.Methods In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio.Results The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events.Conclusions The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)