Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory

Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor

IT-901 is a novel and selective NF-κB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells (CLL) with IT-901 effectively interrupts NF-κB transcriptional activity. CLL cells exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation and ATP production, and activate intrinsic apoptosis. Inhibition of NF-κB signaling in stromal and myeloid cells, both tumor-supportive elements, fails to induce apoptosis, but impairs NF-κB-driven expression of molecules involved in cell-cell contacts and immune responses, essential elements in creating a pro-leukemic niche. The consequence is that accessory cells do not protect CLL cells from IT-901-induced apoptosis. In this context, IT-901 shows synergistic activity with ibrutinib, arguing in favor of combination strategies. IT-901 is also effective in primary cells from patients with Richter syndrome (RS). Its anti-tumor properties are confirmed in xenograft models of CLL and in RS patient-derived xenografts, with documented NF-κB inhibition and significant reduction of tumor burden. Together, these results provide pre-clinical proof of principle for IT-901 as a potential new drug in CLL and RS

La relazione di cura tra legge e prassi. Un'indagine comparativa tra Italia, Francia, Spagna e Inghilterra

Dicembre 2017: il Parlamento italiano approva la legge n. 219, che parla di relazione di cura, di consenso informato, di disposizioni anticipate di trattamento, di cure palliative, di pianificazione condivisa delle cure. Tutti temi sui quali da tempo i legislatori di altri Paesi, europei e non solo, erano già intervenuti. La comparsa di un testo nella G.U. non è però che il primo passo verso la realizzazione degli obiettivi in esso dichiarati, essendo necessari sforzi di comprensione e di interpretazione, di formazione del personale, di riorganizzazione dei servizi; da qui l’idea di andare sul campo per verificare – soprattutto là dove l’esperienza figura già maturata – quale sia il livello di conoscenza delle leggi fra i soggetti professionalmente impegnati nel mondo della sanità e quanto di ciò che esse promuovono, consentono o impongono, si traduce effettivamente in pratica quotidiana dei reparti. In questo volume sono riportati i risultati di questo confronto fra law in the books e law in action, frutto di un’indagine che ha coinvolto decine di professionisti di varia estrazione, operanti in strutture ospedaliere di Italia, Francia, Spagna e Inghilterra