Gabriele Malaspina, marchese di Fosdinovo

This book focuses on one of the prime movers in the unification of Lunigiana – a region which at the time was still broken up into a myriad of tiny feudal holdings, almost all in the hands of the various branches of the Malaspina family. The process of unification began in the fifteenth century, when various areas of the region were conquered by Milan and Florence, which also divided between them the hegemony of the remaining independent territories, while Genoa too displayed an interest in expansion in the region. As a result it became crucial for the local lords to manoeuvre between the various forces at play to maintain the independence of their own little states. Among the figures who displayed the greatest dexterity in this was Gabriele Malaspina, who became a leading player on the stage of local history. The book starts by illustrating the period in which Malaspina succeeded in obtaining his political independence, and then goes on to analyse the phase in which his policy came to be characterised by an absolute loyalty to Florence. Finally the book addresses the last part of the Marquis's life, marked by a progressive distancing from the Florentine alliance in favour of other entities, in which he nevertheless always succeeded in maintaining his independence.Al centro di questo volume è uno degli attori principali nel processo di riunificazione della Lunigiana – regione allora suddivisa in tante piccole signorie, quasi tutte nelle mani dei vari rami della famiglia Malaspina – che avvenne nel XV secolo, quando Milano e Firenze vi conquistarono diversi territori e si spartirono l'egemonia sui restanti territori autonomi, mentre anche Genova si mostrò interessata all'espansione in quella zona. Per i signori locali divenne quindi fondamentale riuscire a destreggiarsi fra le varie forze in gioco per mantenere l'indipendenza del proprio piccolo stato, e fra i personaggi che più risaltano per questa loro abilità e per il ruolo giocato nella storia locale spicca Gabriele Malaspina. Il libro inizia mostrando la situazione della Lunigiana al momento in cui il Malaspina ottenne la propria indipendenza politica, per poi analizzare il periodo in cui la politica marchionale si caratterizzò per la sua assoluta fedeltà all'amicizia fiorentina, e quindi la parte finale della vita del marchese, in cui si assiste a un progressivo allontanamento dall'alleanza fiorentina in favore di altri soggetti, ma in cui riuscì sempre a mantenere la sua indipendenza

Gabriele Malaspina, marchese di Fosdinovo

This book focuses on one of the prime movers in the unification of Lunigiana – a region which at the time was still broken up into a myriad of tiny feudal holdings, almost all in the hands of the various branches of the Malaspina family. The process of unification began in the fifteenth century, when various areas of the region were conquered by Milan and Florence, which also divided between them the hegemony of the remaining independent territories, while Genoa too displayed an interest in expansion in the region. As a result it became crucial for the local lords to manoeuvre between the various forces at play to maintain the independence of their own little states. Among the figures who displayed the greatest dexterity in this was Gabriele Malaspina, who became a leading player on the stage of local history. The book starts by illustrating the period in which Malaspina succeeded in obtaining his political independence, and then goes on to analyse the phase in which his policy came to be characterised by an absolute loyalty to Florence. Finally the book addresses the last part of the Marquis's life, marked by a progressive distancing from the Florentine alliance in favour of other entities, in which he nevertheless always succeeded in maintaining his independence

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Gabriele Malaspina, marchese di Fosdinovo : Condotte, politica e diplomazia nella Lunigiana del Rinascimento

This book focuses on one of the prime movers in the unification of Lunigiana – a region which at the time was still broken up into a myriad of tiny feudal holdings, almost all in the hands of the various branches of the Malaspina family. The process of unification began in the fifteenth century, when various areas of the region were conquered by Milan and Florence, which also divided between them the hegemony of the remaining independent territories, while Genoa too displayed an interest in expansion in the region. As a result it became crucial for the local lords to manoeuvre between the various forces at play to maintain the independence of their own little states. Among the figures who displayed the greatest dexterity in this was Gabriele Malaspina, who became a leading player on the stage of local history. The book starts by illustrating the period in which Malaspina succeeded in obtaining his political independence, and then goes on to analyse the phase in which his policy came to be characterised by an absolute loyalty to Florence. Finally the book addresses the last part of the Marquis\u27s life, marked by a progressive distancing from the Florentine alliance in favour of other entities, in which he nevertheless always succeeded in maintaining his independence.Al centro di questo volume \ue8 uno degli attori principali nel processo di riunificazione della Lunigiana – regione allora suddivisa in tante piccole signorie, quasi tutte nelle mani dei vari rami della famiglia Malaspina – che avvenne nel XV secolo, quando Milano e Firenze vi conquistarono diversi territori e si spartirono l\u27egemonia sui restanti territori autonomi, mentre anche Genova si mostr\uf2 interessata all\u27espansione in quella zona. Per i signori locali divenne quindi fondamentale riuscire a destreggiarsi fra le varie forze in gioco per mantenere l\u27indipendenza del proprio piccolo stato, e fra i personaggi che pi\uf9 risaltano per questa loro abilit\ue0 e per il ruolo giocato nella storia locale spicca Gabriele Malaspina. Il libro inizia mostrando la situazione della Lunigiana al momento in cui il Malaspina ottenne la propria indipendenza politica, per poi analizzare il periodo in cui la politica marchionale si caratterizz\uf2 per la sua assoluta fedelt\ue0 all\u27amicizia fiorentina, e quindi la parte finale della vita del marchese, in cui si assiste a un progressivo allontanamento dall\u27alleanza fiorentina in favore di altri soggetti, ma in cui riusc\uec sempre a mantenere la sua indipendenza

Gabriele Malaspina, marchese di Fosdinovo

This book focuses on one of the prime movers in the unification of Lunigiana – a region which at the time was still broken up into a myriad of tiny feudal holdings, almost all in the hands of the various branches of the Malaspina family. The process of unification began in the fifteenth century, when various areas of the region were conquered by Milan and Florence, which also divided between them the hegemony of the remaining independent territories, while Genoa too displayed an interest in expansion in the region. As a result it became crucial for the local lords to manoeuvre between the various forces at play to maintain the independence of their own little states. Among the figures who displayed the greatest dexterity in this was Gabriele Malaspina, who became a leading player on the stage of local history. The book starts by illustrating the period in which Malaspina succeeded in obtaining his political independence, and then goes on to analyse the phase in which his policy came to be characterised by an absolute loyalty to Florence. Finally the book addresses the last part of the Marquis's life, marked by a progressive distancing from the Florentine alliance in favour of other entities, in which he nevertheless always succeeded in maintaining his independence

Poteri, relazioni, guerra nel regno di Ferrante d’Aragona. Studi sulle corrispondenze diplomatiche.

Il volume raccoglie una serie di studi nati attorno all’impresa di edizione delle corrispondenze diplomatiche milanesi e fiorentine da Napoli in età aragonese, in particolare negli anni di Ferrante d’Aragona (1458-’94). Essi spaziano dalla storia della guerra e del territorio alla prosopografia, dalla ricostruzione delle reti di relazione negli ambienti cortigiani alla politica internazionale, dalla geografia feudale ai conflitti tra la monarchia e l’aristocrazia. Ne risulta un importante incremento delle nostre conoscenze sul regno di Napoli, reso possibile dallo studio ampio e sistematico della fonte diplomatica, che viene valutata nei suoi differenti gradi di attendibilità con il concorso delle altre fonti disponibili, regnicole e non, e utilizzata nella varietà delle sue potenzialità informative

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients

Antitumor effects of novel co-drugs linking histone deacetylase and ribonucleotide reductase inhibitors in hematological tumors

Combination therapy is the mainstay of anticancer therapy due to the significant synergistic effects achievable. Now that anticancer drug research turned toward a more molecular targeted approach, the design of dual-target drugs appears to be a new promising strategy with the potential to improve the therapeutic efficacy of the single drug and to reduce the probability of drug induced resistance and cross resistance. In our previous work, we found that 3’-C-methyl-adenosine (3’-Me-Ado), developed by us as a potent ribonucleotide reductase (RR) inhibitor with antitumor activity against both human leukemia and carcinoma cell lines, elicited significant growth inhibitory and apoptotic synergistic effects in promyelocytic leukemia cells in combination with some hydroxamic acid–derived histone deacetylase (HDAC) inhibitors. Also the antiepileptic agent valproic acid (VPA) was shown to inhibit HDAC in tumors and to synergize with a number of anticancer drugs including RR inhibitors. Since VPA is currently used and well tolerated in the clinics, we pursued the development of co-drugs by combining the structures of 3’-Me-Ado and VPA in a single molecule. Thus, the 3’-C-methyladenosine-2’(5’)-O-valproic esters (A157, A167) and the 2’,5’-diester analog (A160) were synthesized and evaluated for their antitumor potential in HL60 and HuT78 cells. Cytotoxicity was studied by the Trypan blue dye exclusion test, whereas apoptosis was evaluated by fluorescence microscopy after staining with acridine orange and etidium bromide. Preliminary results showed that the compounds induced cytotoxic effects with IC50 ranging from 11 and 600 μM and from 32 and 900 μM in HL60 and HuT78 respectively, demonstrating a higher potency when compared with VPA alone (IC50 of about 2.5 mM). However, their apoptotic activity was modest, with the most potent compound A160 showing an AC50 higher than 100 μM in HL60 cells. The western blotting study of the level of acetylated histone H3 demonstrated that the compounds were not capable of inhibiting significantly the HDAC enzymes. Instead, the evaluation of cell cycle distribution by flow cytometry did show a recruitment of treated cells in the G1 phase of the cell cycle, suggesting that the compounds could retain the RR inhibiting activity of 3’-Me-Ado. Further studies are in progress to clarify the mechanism of cytotoxic activity of the synthesized co-drugs

Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis

Objective: To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS. Methods: The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated. Results: CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P < .001 and P < .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS. Conclusion: Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory tes

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-methyladenosine

We synthesized a series of serum-stable covalently linked drugs derived from 3′-C-methyladenosine (3′-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3′-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2′,5′-bis-O-valproyl-3′-C-methyladenosine (A160) and 5′-O-valproyl-3′-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting features as an RR inhibitor. It inhibited RR activity by competing with ATP as an allosteric effector and concomitantly reduced the intracellular deoxyribonucleoside triphosphate (dNTP) pools. A167 represents a novel lead compound, which in contrast to previously used RR nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases