Consumi di tabacco e alcol durante il triennio 2000-2003 tra gli adolescenti delle scuole superiori di Lodi e di Milano (citt\ue0 e Provincia) : risultati di due rilevazioni multicentriche

Tobacco- and alcohol-related behaviors are important public health problems under the sanitary, economic and political point of view; even if the negative consequences of these substances' use and abuse are clear and well recognized, the prevalence of the phenomenon remains however high. Therefore to put in action prevention effective procedures, it is useful to know causes and consequences of the behaviour, but also to be able to quantify them and follow them up. This research is aimed at assessing the spread of tobacco's and alcohol's consumptions among students attending high school in Lodi and Milano (City and Province) during school year 2002-2003 and allows to compare these data with those obtained through a similar study carried out during school year 2000-2001. Data have been collected using a translated and adapted version of the YRBSS questionnaire implemented by CDC to monitor the prevalence of high-risk behaviors among U.S. teens. Tobacco habits appears still high but have not increased in the considered period, while alcohol-related behaviors are growing in popularity and performed by a greater number of adolescents,compared with what happened three years earlier This proves to be particolarly true for girls. Prevention implications are presented on the basis of these results

Complementarity-determining region clustering may cause CAR-T cell dysfunction

Chimeric antigen receptor (CAR)-T cell therapy is rapidly advancing as cancer treatment, however, designing an optimal CAR remains challenging. A single-chain variable fragment (scFv) is generally used as CAR targeting moiety, wherein the complementarity-determining regions (CDRs) define its specificity. We report here that the CDR loops can cause CAR clustering, leading to antigen-independent tonic signalling and subsequent CAR-T cell dysfunction. We show via CARs incorporating scFvs with identical framework and varying CDR sequences that CARs may cluster on the T cell surface, which leads to antigen-independent CAR-T cell activation, characterized by increased cell size and interferon (IFN)-& gamma; secretion. This results in CAR-T cell exhaustion, activation-induced cell death and reduced responsiveness to target-antigen-expressing tumour cells. CDR mutagenesis confirms that the CAR-clustering is mediated by CDR-loops. In summary, antigen-independent tonic signalling can be induced by CDR-mediated CAR clustering, which could not be predicted from the scFv sequences, but could be tested for by evaluating the activity of unstimulated CAR-T cells