Characterization of GABAB-receptor mediated neurotransmission in the human cortex by paired-pulse TMS–EEG

GABAB-receptor (GABABR) mediated inhibition is important in regulating neuronal excitability. The paired-pulse transcranial magnetic stimulation (TMS) protocol of long-interval intracortical inhibition (LICI) likely reflects this GABABergic inhibition. However, this view is based on indirect evidence from electromyographic (EMG) studies. Here we combined paired-pulse TMS with simultaneous electroencephalography (paired-pulse TMS–EEG) and pharmacology to directly investigate mechanisms of LICI at the cortical level. We tested the effects of a conditioning stimulus (CS100) applied 100 ms prior to a test stimulus (TS) over primary motor cortex on TS-evoked EEG-potentials (TEPs). Healthy subjects were given a single oral dose of baclofen, a GABABR agonist, or diazepam, a positive modulator at GABAARs, in a placebo-controlled, pseudo-randomized double-blinded crossover study. LICI was quantified as the difference between paired-pulse TEPs (corrected for long-lasting EEG responses by the conditioning pulse) minus single-pulse TEPs. LICI at baseline (i.e. pre-drug intake) was characterized by decreased P25, N45, N100 and P180 and increased P70 TEP components. Baclofen resulted in a trend towards the enhancement of LICI of the N45 and N100, and significantly enhanced LICI of the P180. In contrast, diazepam consistently suppressed LICI of late potentials (i.e. N100, P180), without having an effect on LICI of earlier (i.e. P25, N45 and P70) potentials. These findings demonstrate for the first time directly at the system level of the human cortex that GABABR-mediated cortical inhibition contributes to LICI, while GABAAR-mediated inhibition occludes LICI. Paired-pulse TMS–EEG allows investigating cortical GABABR-mediated inhibition more directly and specifically than hitherto possible, and may thus inform on network abnormalities caused by disordered inhibition, e.g. in patients with schizophrenia or epilepsy

Funzione e figura delle architetture pubbliche e servizi per lo svilupppo sostenibile delle aree metropolitane. I casi confrontati dell'area metropolitana milanese e della "città di Fondazione" nel Mezzogiorno d'Italia, in RICERCHE IN ARCHITETTURA. La Zolla nella dispersione delle aree metropolitane. Resoconti della Ricerca MURST 2000 Funzione e figura delle architetture pubbliche e servizi per lo sviluppo sostenibile delle aree metropolitane: Firenze, Milano, Napoli, a cura di Salvatore Bisogni, responsabili per le singole unità: Salvatore Bisogni, Guido Canella, Gian Luigi Maffei, Franco Purini

Resoconto di ricerca dell'Unità di Milano nel quadro dei resoconti della Ricerca nazionale cofinanziamento 2000 Ministero dell'Università e della Ricerca Scientifica e Tecnologica coordinata fra le Facoltà di architettura dell'Università degli Studi di Firenze, del Politecnico di Milano, dell'Università degli Studi di Napoli Federico II, dell'Università di Mestre - IUAV; coordinatore scientifico nazionale Salvatore Bisogni, responsabili per le singole unità: Salvatore Bisogni, Guido Canella, Gian Luigi Maffei, Franco Purini

Aerobic Growth of Rhodococcus aetherivorans BCP1 Using Selected Naphthenic Acids as the Sole Carbon and Energy Sources

Naphthenic acids (NAs) are an important group of toxic organic compounds naturally occurring in hydrocarbon deposits. This work shows that Rhodococcus aetherivorans BCP1 cells not only utilize a mixture of eight different NAs (8XNAs) for growth but they are also capable of marked degradation of two model NAs, cyclohexanecarboxylic acid (CHCA) and cyclopentanecarboxylic acid (CPCA) when supplied at concentrations from 50 to 500 mgL-1. The growth curves of BCP1 on 8XNAs, CHCA, and CPCA showed an initial lag phase not present in growth on glucose, which presumably was related to the toxic effects of NAs on the cell membrane permeability. BCP1 cell adaptation responses that allowed survival on NAs included changes in cell morphology, production of intracellular bodies and changes in fatty acid composition. Transmission electron microscopy (TEM) analysis of BCP1 cells grown on CHCA or CPCA showed a slight reduction in the cell size, the production of EPS-like material and intracellular electron-transparent and electron-dense inclusion bodies. The electron-transparent inclusions increased in the amount and size in NA-grown BCP1 cells under nitrogen limiting conditions and contained storage lipids as suggested by cell staining with the lipophilic Nile Blue A dye. Lipidomic analyses revealed significant changes with increases of methyl-branched (MBFA) and polyunsaturated fatty acids (PUFA) examining the fatty acid composition of NAs-growing BCP1 cells. PUFA biosynthesis is not usual in bacteria and, together with MBFA, can influence structural and functional processes with resulting effects on cell vitality. Finally, through the use of RT (Reverse Transcription)-qPCR, a gene cluster (chcpca) was found to be transcriptionally induced during the growth on CHCA and CPCA. Based on the expression and bioinformatics results, the predicted products of the chcpca gene cluster are proposed to be involved in aerobic NA degradation in R. aetherivorans BCP1. This study provides first insights into the genetic and metabolic mechanisms allowing a Rhodococcus strain to aerobically degrade NAs

Lung Ultrasound Improves Outcome Prediction over Clinical Judgment in COVID-19 Patients Evaluated in the Emergency Department

In the Emergency Department (ED), the decision to hospitalize or discharge COVID-19 patients is challenging. We assessed the utility of lung ultrasound (LUS), alone or in association with a clinical rule/score. This was a multicenter observational prospective study involving six EDs (NCT046291831). From October 2020 to January 2021, COVID-19 outpatients discharged from the ED based on clinical judgment were subjected to LUS and followed-up at 30 days. The primary clinical outcome was a composite of hospitalization or death. Within 393 COVID-19 patients, 35 (8.9%) reached the primary outcome. For outcome prognostication, LUS had a C-index of 0.76 (95%CI 0.68–0.84) and showed good performance and calibration. LUS-based classification provided significant differences in Kaplan–Meier curves, with a positive LUS leading to a hazard ratio of 4.33 (95%CI 1.95–9.61) for the primary outcome. The sensitivity and specificity of LUS for primary outcome occurrence were 74.3% (95%CI 59.8–88.8) and 74% (95%CI 69.5–78.6), respectively. The integration of LUS with a clinical score further increased sensitivity. In patients with a negative LUS, the primary outcome occurred in nine (3.3%) patients (p < 0.001 vs. unselected). The efficiency for rule-out was 69.7%. In unvaccinated ED patients with COVID-19, LUS improves prognostic stratification over clinical judgment alone and may support standardized disposition decisions

Misure critiche. Nuova serie. A. 9, n. 2 (2010)

N.S. A. 9, n. 2 (2010): Cardillo A., Ludovico Castelvetro: sul “traslatare”, P. 5 ; Falardo D., “Lezioni” sul “Perí ýpsous”: Ms. Campori 843 della Biblioteca Estense, P. 22 ; De Caprio V., Pascoli e i ritorni di Ulisse, P. 30 ; Troiano R., Tradizioni regionali dialettali nella critica letteraria di Antonio Piromalli, P. 54 ; Paglia L., Percorso metodologico di lettura e di scrittura critica su un testo poetico, P. 67 ; Iannaco D., Due antologie di poeti contemporanei, P. 88 ; Tuscano P., Alvaro negli anni di Gennaro Mercogliano, P. 97 ; Napoli A., Nata il settimo giorno della creazione: il “Canto dell’amore assente” di Sauro Damiani, P. 105 ; Acanfora N., Il calcio nell’immaginario letterario tra “short story” e “teatro”. Rassegna bibliografica (2005-2010), P. 111 ; Annalisa Pontis, recensione a, Paola Daniela Giovanelli, Goldoni a Bologna, Roma, Bulzoni 2008, P. 135 ; Leone G., recensione a, Valeria Giannantonio, Oltre Vico. L’identità del passato a Napoli e Milano fra ‘700 e ‘800, Lanciano, Carabba 2009, P. 138 ; Moliterni, F., recensione a, In un concerto di voci amiche. Studi di letteratura italiana dell’Otto e Novecento in onore di Donato Valli, a cura di Marinella Cantelmo e Antonio Lucio Giannone (I tomo); Antonio Lucio Giannone (II tomo), Galatina, Congedo 2008, P. 140 ; Ferreri D., recensione a, Lavinia Spalanca, I fiori del deserto. Sbarbaro tra poesia e scienza, con testimonianze inedite, Genova, San Marco dei Giustiniani 2008, P. 143 ; Lucia C., recensione a, Raffaele Viviani, Poesie, Napoli, Guida 2010, P. 148 ; Filieri E., Antonio Lucio Giannone, Modernità del Salento. Scrittori, critici e artisti del Novecento e oltre, Galatina, Congedo 2009, P. 151 ; Nuovo L., Madotta L., recensione a, Salvatore Di Pasqua, Letteratura “come” pedagogia. La natura di un’analogia, Trieste, Eut 2010, P. 154 ; Troiano R., recensione a, Francesca Malagnini, Storia della lingua italiana e Didattica. Percorso di educazione linguistica e analisi di alcuni testi in prosa, Lecce, Pensa MultiMedia 2010, P. 157 ; Annibaldis G., recensione a, Pietro Sisto, “Legato son, perch’io stesso mi strinsi”. Storie e immagini di animali nella letteratura italiana, Pisa-Roma, Fabrizio Serra 2010, P. 162 ; Albano V., recensione a, Alessandro Acquarone, Pratica ed etica del management teatrale, Milano, Franco Angeli 2009, P. 164 ; Albano V., recensione a, Rancesco Silvestri, Questo legno è ancora vivo, Ragusa, EdiArgo 2008, P. 165 ; Acanfora N., recensione a, Giancarlo Cauteruccio, Panza, crianza, ricordanza. Tre pezzi dalla solitudine, Firenze, Edizioni della Meridiana 2008, P. 167 ; Acanfora N., recensione a, Emma Dante, Via Castellana Bandiera, Milano, Rizzoli 2008, P. 171 ; Elia G. S., recensione a, Marco I. De Santis, Lettere dagli argonauti, Bari, La Vallisa 2007, P. 177 ; Iannaco D., recensione a, Franco Manzoni, In fervida assenza, Milano, Raccolto 2010, P. 178 ; Napoli A., recensione a, Giancarlo Pontiggia, Stazioni, Varese, NEM 2010, P. 180 ; Copioli R., recensione a, Adriano Napoli, Le api dell’invisibile. Poeti italiani 1968-2008, Milano, Medusa 2010, P. 181

Data_Sheet_1.pdf

<p>Naphthenic acids (NAs) are an important group of toxic organic compounds naturally occurring in hydrocarbon deposits. This work shows that Rhodococcus aetherivorans BCP1 cells not only utilize a mixture of eight different NAs (8XNAs) for growth but they are also capable of marked degradation of two model NAs, cyclohexanecarboxylic acid (CHCA) and cyclopentanecarboxylic acid (CPCA) when supplied at concentrations from 50 to 500 mgL^-1. The growth curves of BCP1 on 8XNAs, CHCA, and CPCA showed an initial lag phase not present in growth on glucose, which presumably was related to the toxic effects of NAs on the cell membrane permeability. BCP1 cell adaptation responses that allowed survival on NAs included changes in cell morphology, production of intracellular bodies and changes in fatty acid composition. Transmission electron microscopy (TEM) analysis of BCP1 cells grown on CHCA or CPCA showed a slight reduction in the cell size, the production of EPS-like material and intracellular electron-transparent and electron-dense inclusion bodies. The electron-transparent inclusions increased in the amount and size in NA-grown BCP1 cells under nitrogen limiting conditions and contained storage lipids as suggested by cell staining with the lipophilic Nile Blue A dye. Lipidomic analyses revealed significant changes with increases of methyl-branched (MBFA) and polyunsaturated fatty acids (PUFA) examining the fatty acid composition of NAs-growing BCP1 cells. PUFA biosynthesis is not usual in bacteria and, together with MBFA, can influence structural and functional processes with resulting effects on cell vitality. Finally, through the use of RT (Reverse Transcription)-qPCR, a gene cluster (chcpca) was found to be transcriptionally induced during the growth on CHCA and CPCA. Based on the expression and bioinformatics results, the predicted products of the chcpca gene cluster are proposed to be involved in aerobic NA degradation in R. aetherivorans BCP1. This study provides first insights into the genetic and metabolic mechanisms allowing a Rhodococcus strain to aerobically degrade NAs.</p

KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

In recent years, the outcome of mantle cell lymphoma has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of mantle cell lymphoma patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in mantle cell lymphoma, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase III trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the MIPI-genetic. The MIPI-g improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-years progression free survival and overall survival of 72.0% and 94.5%); ii) intermediate-risk patients (4-years progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-years progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk mantle cell lymphoma patients for whom novel therapeutic strategies need to be investigated. (Trial registered at clinicaltrials.gov identifier: NCT02354313)