Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Analisi dell’adeguamento dell’infrastruttura esistente in relazione al progetto di Residenza Universitaria nel Comparto Battiferro a Bologna

L’elaborato di tesi affronta il caso di studio relativo al progetto di riassetto viabilistico nell’ambito della realizzazione, in corso d’opera, del nuovo Campus Universitario Navile, nella prima periferia a nord di Bologna. In particolare è stata analizzata la situazione di Vicolo del Pellegrino, strada di quartiere destinata a servire uno studentato di prossima realizzazione. Un aspetto particolarmente vincolante è costituito dalla presenza di un’alberatura tutelata per salvaguardare la quale sono stati presi quanti più accorgimenti possibili. Vengono proposte due differenti soluzioni progettuali: - soluzione A: prevede la realizzazione la realizzazione di una nuova sede stradale (strada di tipologia F2, per un tratto di 308 m) per Vicolo del Pellegrino, un nuovo percorso ciclopedonale (di lunghezza 280 m) sull’attuale sedime di quest’ultimo, un ulteriore tratto ciclabile a fondo naturale (di lunghezza 110 m) e un parcheggio a raso; - soluzione B: si differenzia principalmente per la scelta di non realizzare alcun nuovo tratto stradale, limitandosi a prevedere una minirotatoria per assicurare comunque una corretta viabilità, oltre ai percorsi ciclopedonali e al parcheggio a raso nelle vicinanze dello studentato. Il progetto comprende anche un impianto di pubblica illuminazione progettato sia per la nuova strada che per i percorsi ciclopedonali. Inoltre, al fine di stimare i costi di intervento e mettere a confronto le due soluzioni progettuali proposte, vengono redatti un computo metrico estimativo e un quadro economico generale e viene effettuato uno studio riguardante gli oneri accessori dovuti ad emissioni inquinanti e consumi energetici. Dal confronto emerge come la soluzione A, più funzionale e caratterizzata da una maggiore accessibilità del comparto, sia caratterizzata da un importo dei lavori notevolmente più elevato e da un impatto ambientale maggiore rispetto alla soluzione B, preferibile dal punto di vista economico e ambientale

Quantification of the enantiomeric excess of two APIs by means of near infrared spectroscopy and chemometrics

A method for the quantification of the enantiomeric excess of two pharmaceutical active ingredients (ibuprofen and epinephrine) in the solid state based on coupling near infrared spectroscopy and chemometrics is proposed. In the case of ibuprofen, in the absence of excipients, the method resulted in an accurate prediction of the enantiopurity of the validation samples (RMSEP <2.0% and practically no bias). On the other hand, the use of "matrix-matched" standards, including the most commonly used excipients, allowed to extend the applicability of the approach also to the analysis of commercial drugs (RMSEP = 7.0%). As far as epinephrine is concerned, very accurate results were obtained (RMSEP<2% and bias = 0.5%). (C) 2014 Elsevier B.V. All rights reserved

Giovanni Quinto

Un "buco nero" della nostra storia, non solo dell'arte, il Barocco veronese, viene esplorato in questo libro. \uc8 una "discesa agli inferi" della pittura, dopo la pionieristica prospezione della mostra di Castelvecchio a Verona nel 1978. Le immagini emergono quasi sempre nuove, anche per gli specialisti