Characterization and Investigation of Benzylic Carbenium Ion and Carbanion Ion-Diradical Intermediates With 3,5-Disubstituted (pi)-Donors/Acceptors

High-spin magnetic materials have been based on monomeric units that contain metals. Far less research has been done to develop and characterize alternative high-spin building blocks consisting of mostly organic subunits. To date, there exists a small class of known high-spin organomagnetic building blocks. These organic building blocks are comprised of neutral intermediates such as diradicals, nitrenes, and carbenes. The work presented in this text will show that a novel class of high-spin intermediates also exists that derives from ionic rather than neutral intermediates. Previous density functional theory (DFT) computations by Winter and Falvey identified a number of ion-diradicals that have favorable triplet ground states. For instance, the 3,5-bis(dimethylamino)benzyl carbenium ion, and 2-(3,5-dinitrophenyl)-1,3-dithiane carbanion, have singlet-triplet energy gaps (ΔESTs) of +1.9 and +0.3 kcal/mol, respectively. Ion-diradicals are based on a general framework whereby either an electron deficient or electron rich exocyclic center is attached to a benzene ring that contains two π-electron withdrawing or donating groups meta with respects to this site. The objective of chapter 2 is to identify the electronic spin state of the 3,5-bis(dimethylamino)benzyl carbenium ion. We have shown that this carbenium ion can be generated from C-O bond heterolysis of 3,5-bis(dimethylamino)benzyl esters and alcohols when photolyzed in polar protic solvents (e.g. methanol, 2-propanol, 2,2,2-trifluoroethanol). Our product studies show that indeed the 3,5-bis(dimethylamino)benzyl ethers are formed from this process, however an unexpected reduction product (3,5-bis(dimethylamino)toluene) is also observed. The reduction product here aptly demonstrates how an ion-diradical could be generated. Formal one electron transfer from a NMe2 group to the exocyclic benzylic carbenium ion center, creates a triplet cation diradical (ion-diradical) intermediate, which eventually leads to the formation of the 3,5-bis(dimethylamino)toluene product observed in all photolysis experiments. Chapters 4-6 investigates whether ion-diradicals can be generated from anionic exocyclic centers that have meta π-acceptor groups (e.g. NO2, CN, CO2R). Computations, NMR, UV-Vis, chemical trapping, H/D exchange, and Evans method magnetic susceptibility experiments demonstrate that the 2-(3,5-dinitrophenyl)-1,3-dithiane carbanion is a persistent and paramagnetic species. Chapters 5 and 6 focuses primarily on characterizing the electronic spin-states to similar anionic systems such as the 3,5-dinitroanilide anion, and 3,5-dinitrobenzyl methoxy ether carbanion

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin. © 2010 Movement Disorder Society

Cardiovascular Risk Prediction in Ankylosing Spondylitis: From Traditional Scores to Machine Learning Assessment

Abstract Introduction The performance of seven cardiovascular (CV) risk algorithms is evaluated in a multicentric cohort of ankylosing spondylitis (AS) patients. Performance and calibration of traditional CV predictors have been compared with the novel paradigm of machine learning (ML). Methods A retrospective analysis of prospectively collected data from an AS cohort has been performed. The primary outcome was the first CV event. The discriminatory ability of the algorithms was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), which is like the concordance-statistic (c-statistic). Three ML techniques were considered to calculate the CV risk: support vector machine (SVM), random forest (RF), and k-nearest neighbor (KNN). Results Of 133 AS patients enrolled, 18 had a CV event. c-statistic scores of 0.71, 0.61, 0.66, 0.68, 0.66, 0.72, and 0.67 were found, respectively, for SCORE, CUORE, FRS, QRISK2, QRISK3, RRS, and ASSIGN. AUC values for the ML algorithms were: 0.70 for SVM, 0.73 for RF, and 0.64 for KNN. Feature analysis showed that C-reactive protein (CRP) has the highest importance, while SBP and hypertension treatment have lower importance. Conclusions All of the evaluated CV risk algorithms exhibit a poor discriminative ability, except for RRS and SCORE, which showed a fair performance. For the first time, we demonstrated that AS patients do not show the traditional ones used by CV scores and that the most important variable is CRP. The present study contributes to a deeper understanding of CV risk in AS, allowing the development of innovative CV risk patient-specific models

Patient-reported impact of spondyloarthritis on work disability and working life: The ATLANTIS survey

44noopenopenRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study groupRamonda, Roberta; Marchesoni, Antonio; Carletto, Antonio; Bianchi, Gerolamo; Cutolo, Maurizio; Ferraccioli, Gianfranco; Fusaro, Enrico; De Vita, Salvatore; Galeazzi, Mauro; Gerli, Roberto; Matucci-Cerinic, Marco; Minisola, Giovanni; Montecucco, Carlomaurizio; Pellerito, Raffaele; Salaffi, Fausto; Paolazzi, Giuseppe; Sarzi-Puttini, Piercarlo; Scarpa, Raffaele; Bagnato, Gianfilippo; Triolo, Giovanni; Valesini, Guido; Punzi, Leonardo; Olivieri, Ignazio; Ortolan, Augusta; Lorenzin, Mariagrazia; Frallonardo, Paola; Giollo, Alessandro; Locaputo, Antonella; Paolino, Sabrina; Simone, Davide; Quartuccio, Luca; Bartoloni, Elena; Luca, Rossella De; Bartoli, Francesca; Sensi, Felice; Caporali, Roberto; Carlo, Marco Di; Roberto, Bortolotti; Atzeni, Fabiola; Costa, Luisa; Ciccia, Francesco; Perrotta, Fabio; Gilio, Michele; ATLANTIS study, Grou

Secondo Protocollo di Implementazione Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2

Questo documento è da intendersi come protocollo di implementazione delle attività nel corso della attuale fase dell’emergenza pandemica e, con lo “Addendum al Documento di Valutazione dei Rischi dedicato al rischio biologico derivante da Sars-CoV-2, protocollo di sicurezza anti contagio, misure di prevenzione e protezione, formazione e informazione”, le Linee guida operative per i lavoratori e le lavoratrici dello “Istituto Nazionale di Astrofisica” Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2 e il Protocollo di implementazione MAB (Musei Archivi Biblioteche) dell’INAF, Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2, dei quali costituisce parte integrante, contiene misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2 per ogni Struttura di Ricerca INAF - Istituto Nazionale di Astrofisica e per la sede della Amministrazione Centrale, e sostituisce integralmente il “Protocollo di Implementazione Fase 2, Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2” adottato con nota Circolare del Direttore Generale del 15 maggio 2020, numero 2482. Le disposizioni contenute nel Decreto del Presidente del Consiglio dei Ministri del 5 Agosto 2020 non si concretano in una totale “ripresa” delle attività di ricerca, ma semplicemente in un “ampliamento”, peraltro assai limitato e condizionato, delle stesse. È quindi necessario, in questa “Fase”, adottare misure che consentano, ove possibile, di svolgere le attività lavorative nella massima sicurezza. Pertanto, il Direttore Generale, d'intesa con il Presidente, il Direttore Scientifico e il Collegio dei Direttori di Struttura, ha avviato un processo volto a definire le azioni propedeutiche all’aggiornamento del “processo di implementazione” delle attività di ricerca e di laboratorio che potranno essere svolte in questa nuova “Fase”, nella consapevolezza che le stesse non devono arrecare alcun nocumento alla salute dei dipendenti dell'Ente e non devono, in alcun modo, favorire, direttamente o indirettamente, una recrudescenza della pandemia in atto, salvaguardando il bene supremo della salute pubblica, costituzionalmente tutelato, e che facciano, quindi, prevalere l'interesse generale sulle logiche puramente individualistiche (Circolare 2 maggio 2020, n. 2083, Allegato 9). Il presente documento tiene conto delle indicazioni contenute nei vari aggiornamenti dei provvedimenti Governativi e delle raccomandazioni delle Autorità Sanitarie Nazionali ed Internazionali, individua e definisce, per tutte le Strutture di Ricerca, le misure di sicurezza che dovranno essere adottate e i dispositivi da utilizzare, suscettibili di ulteriori e/o diverse implementazioni a livello locale, in ragione delle diverse peculiarità delle singole Strutture della specificità dei luoghi, delle esigenze logistiche, delle misure organizzative adottate e di eventuali aggiornamenti delle disposizioni normative. Resta inteso che in base all’evoluzione dello scenario epidemiologico, e nell’ottica della tutela della pubblica sicurezza, le misure indicate potranno essere rimodulate, anche in senso più restrittivo, e dovranno essere immediatamente applicate eventuali, future e più restrittive disposizioni governative Regionali e/o locali. Il Direttore Generale, il Direttore Scientifico e i Direttori di Struttura, ciascuno nell'ambito delle rispettive competenze, individuano idonee procedure di controllo dell'applicazione delle predette misure di sicurezza, con la collaborazione di RSPP, RLS e Medico Competente. I contenuti del documento saranno aggiornati ad ogni variazione della valutazione del rischio e delle misure di contrasto alla diffusione del Sars-CoV-19 da parte degli organi competenti. Ogni sede integra con eventuali indicazioni del Responsabile della Prevenzione e Protezione, del Medico Competente, del Rappresentante dei Lavoratori per la Sicurezza, anche in relazione all’ambiente specifico

Addendum al Documento Valutazione dei Rischi dedicato al rischio biologico derivante da Sars-CoV-2, protocollo di sicurezza anti-contagio misure di prevenzione e protezione formazione e informazione

Documento da allegare al Documento di Valutazione dei Rischi di ogni Struttura di Ricerca INAF - Istituto Nazionale di Astrofisica. Documento approvato con nota Circolare del 15 maggio 2020, numero 2482

Protocollo per l’aggiornamento delle Misure per il contrasto e il contenimento della diffusione del virus SARS-CoV-2/Covid-19 nelle Strutture di Ricerca e nella Sede della Amministrazione Centrale dello Istituto Nazionale di Astrofisica.

Il documento è da intendersi come protocollo per l’aggiornamento delle misure di contrasto alla diffusione dell’epidemia da Covid-19, anche in considerazione dell’emanazione dei nuovi provvedimenti adottati dal Governo e dal Ministero della Salute, di circolari e “comunicazioni” di Ministeri e Autorità competenti, e della legislazione vigente in materia di contrasto alla diffusione dell’epidemia da Covid-19, e contiene linee guida per la revisione e l’aggiornamento dei “Protocolli di sicurezza” adottati a livello locale dalle Strutture di Ricerca e dalla sede della Amministrazione Centrale, tenuto conto della situazione epidemiologica e della necessità di conservare misure efficaci per prevenire e ridurre il rischio di contagio. Il documento tiene conto delle nuove disposizioni normative e, in particolare, del “Protocollo condiviso di aggiornamento delle misure per il contrasto e il contenimento della diffusione del virus SARS-CoV-2/COVID-19 negli ambienti di lavoro”, siglato il 30 giugno 2022 e ha l’obiettivo di fornire indicazioni operative e linee guida aggiornate per garantire l’efficacia delle misure precauzionali di contenimento adottate per contrastare l’epidemia da Covid-19, applicando tutte le misure necessarie allo svolgimento delle attività lavorative nella massima sicurezza, tenendo in particolare conto gli aspetti che riguardano il benessere del personale nell’accezione più ampia del termine. Il documento richiama, inoltre, la necessità di promuovere e favorire, in ogni sistema di prevenzione di qualunque rischio, un ambiente di lavoro sereno, in cui i rapporti interpersonali siano improntati alla correttezza, al reciproco rispetto della libertà e dignità della persona in quanto diritti inviolabili di tutto il personale che a qualsiasi titolo lavora e opera all'interno dell'Istituto, delle lavoratrici e dei lavoratori chiamati ad applicare, a garantire il rispetto del presente documento e di chi ha lavorato per la sua stesura. Atteggiamenti offensivi, molesti, violenti e lesivi della dignità e della professionalità dell’individuo sul luogo di lavoro, oltre a costituire fattori di rischio lavorativo, sono stigmatizzati dai “Codici” adottati dall’Ente

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice