Framing Clement III, (Anti)Pope, 1080-1100. Preface

La vicenda terrena dell’(anti)papa Clemente III e gli sviluppi postumi della sua memoria sono esplorati per mettere in luce sia le complesse dinamiche in cui si inserisce questo ecclesiastico di rango assurto al soglio pontificio in una fase cruciale della riforma della Chiesa, sia le implicazioni legate al prefisso "anti"

Angelitus vivere. Pier Damiani e la perfezione eremitica

This essay analyses Peter Damian’s idea of perfection, by taking into account his texts devoted to the eremitic conversatio avellanita: in particular, Epistles 18, 50, and 109. It answers to the following working question: how is it possible to achieve an ‘angelic’ condition? Particular attention is paid to the ideas of time, space and ascesis

Introduzione: il pellegrinaggio medievale

Il pellegrinaggio non è un fenomeno esclusivamente cristiano, ma nel volgere dii pochi secoli diviene uno dei fenomeni che hanno contribuito nel modo più incisivo e profondo alla costruzione dello spazio cristiano medievale

Adaptation of an i-voting scheme to Italian Elections for Citizens Abroad

We adapt the Ara´ujo-Traor´e protocol to Italian elections, with emphasis on anti-coercion measures. In this short paper we focus on a new method for managing anti-coercion credentials for each voter

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Worsening of myocardial performance index in beta-thalassemia patients despite permanently normal iron load at MRI: A simple and cheap index reflecting cardiovascular involvement?

Abstract Background Iron Overload Cardiomyopathy (IOC) due to repeated transfusions still represents the main cause of death in Thalassemia major (TM) patients. Because iron overload remains asymptomatic for long time, it is important to stratify the patients based on the risk of developing IOC before the appearance of clinical signs of heart failure. The magnetic resonance imaging (MRI) T2* may be useful but it is expensive and its MRI software has limited availability; conventional echocardiographic parameters, although easy availability, remain normal until advanced stages of IOC. Tissue Doppler Imaging (TDI) opened a new way to explore systolic and diastolic function directly or through derived index such as myocardial performance index (MPI) which has a prognostic value in different cardiomyopathies. Methods We enrolled 46 consecutive β-TM patients without clinical signs of heart failure and we tested them with echocardiography in 2011 and again in 2015. MPI of left and right ventricular lateral wall was calculated by TDI. All TM patients had a T2* MRI evaluation of the heart in the year before. Results Despite the absence of significant changes in morphological data at echo and at T2* evaluation, S′ waves of the lateral ventricular wall decrease while time passed, MPI worsened during the follow-up period and the derived systolic pulmonary artery systolic pressure (PAPs) increased in 2015 with respect to 2011. Conclusion TDI and MPI may reveal very early myocardial dysfunction in TM patients despite a normal T2* value. Together with PAPs they should be periodically checked in these patients

A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

May-Hegglin Anomaly, Sebastian Syndrome, Fechtner Syndrome, and Epstein Syndrome Are not Distinct Entities but Represent a Variable Expression of a Single Illness

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects

The multiform motor cortical output: kinematic, predictive and response coding

Observing actions performed by others entails a subliminal activation of primary motor cortex reflecting the components encoded in the observed action. One of the most debated issues concerns the role of this output: Is it a mere replica of the incoming flow of information (kinematic coding), is it oriented to anticipate the forthcoming events (predictive coding) or is it aimed at responding in a suitable fashion to the actions of others (response coding)? The aim of the present study was to disentangle the relative contribution of these three levels and unify them into an integrated view of cortical motor coding. We combined transcranial magnetic stimulation (TMS) and electromyography recordings at different timings to probe the excitability of corticospinal projections to upper and lower limb muscles of participants observing a soccer player performing: (i) a penalty kick straight in their direction and then coming to a full stop, (ii) a penalty kick straight in their direction and then continuing to run, (iii) a penalty kick to the side and then continuing to run. The results show a modulation of the observer's corticospinal excitability in different effectors at different times reflecting a multiplicity of motor coding. The internal replica of the observed action, the predictive activation, and the adaptive integration of congruent and non-congruent responses to the actions of others can coexist in a not mutually exclusive way. Such a view offers reconciliation among different (and apparently divergent) frameworks in action observation literature, and will promote a more complete and integrated understanding of recent findings on motor simulation, motor resonance and automatic imitation