Il cimitero ebraico di Gradisca d'Isonzo

Curatela di un volume della collana Corpus Epitaphiorum Hebraicorum Italiae che riguarda il cimitero ebraico di Gradisca d'Isonzo, istituito nella contea principesca di Gorizia e Gradisca nel periodo dell'appartenenza all'Impero asburgico, unico attualmente in uso nel Goriziano, che comprende la storia del contesto e delle famiglie, la riproduzione di fotografie storiche e attuali delle lapidi con la loro traduzione in italiano

Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation

Objectives The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design. Background Due to its If blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. Methods Twenty-one patients were randomized to receive placebo (n = 10) or ivabradine 5 mg twice daily (n = 11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. Results After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p < 0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88 ± 11 beats/min to 76 ± 11 beats/min, p = 0.011), on standing (from 108 ± 12 beats/min to 92 ± 11 beats/min, p < 0.0001), during 24 h (from 88 ± 5 beats/min to 77 ± 9 beats/min, p = 0.001), and during effort (from 176 ± 17 beats/min to 158 ± 16 beats/min, p = 0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. Conclusions In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia

Dissecting the susceptibility/resistance mechanism of Vitis vinifera for the future control of downy mildew

23CO.NA.VI. 2020 – 8° Convegno Nazionale di Viticoltura, Udine, Italy, July 5-7, 2021openInternationalBothThe Eurasian grapevine (Vitis vinifera), a species cultivated worldwide for high-quality wine production, is extremely susceptible to the agent of downy mildew, Plasmopara viticola. Nevertheless, germplasm from Georgia (Southern Caucasus, the first grapevine domestication centre), characterized by a high genetic variability, showed resistance traits to P. viticola. The cultivar Mgaloblishvili exhibited the most promising phenotype in terms of resistance against P. viticola. Its defence response results in: i) low disease intensity; ii) low sporulation; iii) damaged mycelium; iv) production of antimicrobial compounds such as volatile organic compounds (VOCs), whose effectiveness on the pathogen was evaluated by leafdisc assays. At the transcriptomic level, its resistance mechanism is determined by the differential expression of both resistance and susceptible genes. The resistance genes are related to: i) pathogen recognition through PAMP, DAMP and effector receptors; ii) ethylene signalling pathway; iii) synthesis of antimicrobial compounds (VOCs) and fungal wall degrading enzymes; iv) development of structural barriers (cell wall reinforcement). The first putative susceptible gene was the transcription factor VviLBDIf7 gene, whose validation was carried out by dsRNA (double-stranded RNA) assay. In this work, these unique results on plant-pathogen interaction are reviewed with the aim of developing new strategies to control the disease.openRicciardi, Valentina; Marcianò, Demetrio; Sargolzaei, Maryam; Marrone Fassolo, Elena; Fracassetti, Daniela; Brilli, Matteo; Moser, Mirko; Vahid, Shariati J.; Tavakole, Elahe; Maddalena, Giuliana; Passera, Alessandro; Casati, Paola; Pindo, Massimo; Cestaro, Alessandro; Costa, Alex; Bonza, Maria Cristina; Maghradze, David; Tirelli, Antonio; Failla, Osvaldo; Bianco, Piero Attilio; Quaglino, Fabio; Toffolatti, Silvia Laura; De Lorenzis, GabriellaRicciardi, V.; Marcianò, D.; Sargolzaei, M.; Marrone Fassolo, E.; Fracassetti, D.; Brilli, M.; Moser, M.; Vahid, S.J.; Tavakole, E.; Maddalena, G.; Passera, A.; Casati, P.; Pindo, M.; Cestaro, A.; Costa, A.; Bonza, M.C.; Maghradze, D.; Tirelli, A.; Failla, O.; Bianco, P.A.; Quaglino, F.; Toffolatti, S.L.; De Lorenzis, G

Extensive molecular profiling of squamous cell anal carcinoma in a phase 2 trial population: Translational analyses of the “CARACAS” study

Background: Molecular characteristics of squamous cell anal carcinoma (SCAC) are poorly explored. Immune checkpoint inhibitors showed limited activity in phase I/II trials, but predictive and prognostic biomarkers are lacking. Patients and methods: In the phase II randomised trial CARACAS (NCT03944252), avelumab alone (Arm A) or with cetuximab (Arm B) was tested in pre-treated advanced SCAC , with overall response rate&nbsp;being the primary end-point. On pre-treatment tumour tissue samples, we assessed Human papillomavirus status, programmed-death ligand 1 (PD-L1) expression, mismatch repair&nbsp;proteins expression, tumour mutational burden (TMB) and comprehensive genomic profiling by FoundationOne CDx. Tumour-infiltrating lymphocytes&nbsp;were characterised on haematoxylin-eosine-stained samples. Primary objective was to describe response to immunotherapy in the CARACAS trial population according to molecular and histological characteristics. Secondary objectives were to assess progression-free survival (PFS) and overall survival (OS) according to molecular biomarkers. Results: High PD-L1 (&gt;40 with combined positive score) was significantly more frequent in patients with disease control (p&nbsp;=&nbsp;0.0109). High TMB (&gt;10 mutations per megabase) was related to better OS (hazard ratio (HR)&nbsp;=&nbsp;0.09; 95%confidence interval (CI) 0.01-0.68; p&nbsp;=&nbsp;0.019) and PFS (HR&nbsp;=&nbsp;0.44; 95%CI&nbsp;=&nbsp;0.15-1.27; p&nbsp;=&nbsp;0.129). High expression of PD-L1 conferred longer OS (HR&nbsp;=&nbsp;0.46; 95%CI&nbsp;=&nbsp;0.19-1.08; p&nbsp;=&nbsp;0.075) and PFS (HR&nbsp;=&nbsp;0.42; 95%CI&nbsp;=&nbsp;0.20-0.92; p&nbsp;=&nbsp;0.03). Neither OS (HR&nbsp;=&nbsp;1.30; 95%CI&nbsp;=&nbsp;0.72-2.36; p&nbsp;=&nbsp;0.39) or PFS (HR&nbsp;=&nbsp;1.31; 95%CI&nbsp;=&nbsp;0.74-2.31; p&nbsp;=&nbsp;0.357) was affected by high (&gt;1.2) Tumour-infiltrating lymphocytes count. High TMB and PD-L1identified patients were with significantly better OS (HR&nbsp;=&nbsp;0.33; 95%CI&nbsp;=&nbsp;0.13-0.81; p&nbsp;=&nbsp;0.015) and PFS (HR&nbsp;=&nbsp;0.48; 95%CI&nbsp;=&nbsp;0.23-1.00; p&nbsp;=&nbsp;0.015). Conclusions: To our knowledge, TranslaCARACAS is the first study to document prognostic role of TMB and PD-L1 in advanced SCAC patients treated with immune checkpoint inhibitors